{"gene":"PF3D7_0406200","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":1994,"finding":"Pfs16 is localized to the parasitophorous vacuole membrane (PVM) of P. falciparum gametocytes. Purification of PVMs from mature and immature gametocytes combined with immunoelectron microscopy established this localization. During gametogenesis, the PVM is shed along with the RBC membrane, and Pfs16 is retained on the disintegrating membrane; in a minority of cases, Pfs16 can be retained on the gamete surface. First expression was estimated at 35 hours post-merozoite invasion in sexually committed ring stages.","method":"Immunofluorescence assay, immunoelectron microscopy, PVM purification from gametocytes","journal":"Molecular and biochemical parasitology","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct subcellular fractionation (PVM purification) combined with immunoelectron microscopy, replicated by subsequent independent studies","pmids":["7935618"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1994,"finding":"Pfs16 is localized specifically to the parasitophorous vacuole membrane (PVM) in gametocytes, and during gametogenesis when the PVM disintegrates, the antigen is detected on multilaminated whorls (remains of the PVM) and not on the gamete plasma membrane. Pfs16 is also present on membranes surrounding cytosomes and food vacuoles within the parasite cytoplasm, and on structures believed to be Garnham bodies in the host cell cytoplasm.","method":"Immunoelectron microscopy","journal":"Parasitology","confidence":"High","confidence_rationale":"Tier 2 / Strong — immunoelectron microscopy with precise subcellular resolution, independently corroborated by PMID:7935618","pmids":["8159458"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1991,"finding":"Pfs16 encodes a 157-amino-acid, 16-kDa integral membrane protein with a putative N-terminal signal sequence, a hydrophobic membrane anchor, and a highly hydrophilic C-terminal region. The protein is expressed on the surface of macrogametes and sporozoites but not in asexual erythrocytic stages, as demonstrated by immunofluorescence and immunoelectron microscopy with protein A-gold.","method":"cDNA cloning, Western blot, immunofluorescence assay, immunoelectron microscopy (protein A-gold)","journal":"Molecular and biochemical parasitology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (molecular cloning, Western blot, IEM) in a single study; independently replicated","pmids":["2038355"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1997,"finding":"Expression of Pfs16 is induced immediately following invasion of a red blood cell by sexually committed merozoites and continues throughout gametocytogenesis and in macrogametes. Regulation is at the level of transcription initiation and is also modulated by a post-transcriptional process, as shown by comparative analysis of promoter activity, RNA levels (in situ hybridization at single-cell level), and de novo protein synthesis rates.","method":"Promoter-reporter transfection assay, Northern blot, in situ hybridization, metabolic labeling of de novo protein synthesis","journal":"Molecular and biochemical parasitology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (promoter activity, RNA quantification, single-cell ISH, metabolic labeling) in one study","pmids":["9364968"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1999,"finding":"The pfs16 promoter is activated at the onset of gametocytogenesis (in sexually committed ring-stage parasites), marking the earliest developmental switch in sexual differentiation. The regions of the pfs16 promoter essential for high transcriptional activity were identified by deletion analysis using transfection of P. falciparum and P. gallinaceum.","method":"Promoter deletion analysis, P. falciparum and P. gallinaceum transfection with reporter constructs","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — functional promoter dissection in two Plasmodium species with reporter assays, multiple constructs tested","pmids":["9891033"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium gallinaceum","strain":""}]},{"year":2004,"finding":"Targeted disruption of the Pfs16 gene by homologous recombination (three independent clones confirmed) resulted in: (1) absence of full-length Pfs16 transcripts and PVM-localized 16 kDa protein; (2) expression of a 14 kDa truncated protein mislocalized to an unidentified double-membrane compartment; (3) significant reduction in gametocyte production; (4) preliminary evidence of impaired male gametocyte exflagellation in vitro. Pfs16 is not essential for sexual development but is required for optimal gametocyte production.","method":"Targeted gene disruption by homologous recombination, RT-PCR, Western blot, immunofluorescence, exflagellation assay","journal":"Molecular and biochemical parasitology","confidence":"High","confidence_rationale":"Tier 2 / Strong — three independent knockout clones confirmed by Southern blot and molecular analysis, multiple orthogonal readouts","pmids":["14698439"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"Pfs16 and Pfpeg3/mdv1 proteins co-localize in the PVM and in all derived membranous structures of stage II gametocytes, including multi-laminate membrane whorls of circular clefts in the erythrocyte cytoplasm, membranes of food vacuoles, and distinct cleft-like structures in the erythrocyte cytoplasm, as shown by immunoelectron microscopy.","method":"Immunoelectron microscopy, immunofluorescence, co-expression analysis","journal":"Experimental parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — immunoelectron microscopy co-localization, single lab, but orthogonal to prior PVM localization findings","pmids":["17367781"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"finding":"The 53 C-terminal amino acids of Pfs16 (appended to a GFP reporter already containing the N-terminal secretory signal) are sufficient for targeting to and retention on the PVM. Removal of the 11 C-terminal amino acids did not prevent PVM targeting but reduced membrane retention. A sequence motif identified in the C-terminal targeting region is shared with seven other known PVM proteins. Additionally, the region between the N-terminal signal sequence and the transmembrane domain (not required for PVM targeting) was found to be involved in 'capping'—concentration of native Pfs16 and full-length Pfs16-GFP at the ends of the gametocyte during emergence from the PVM and RBC.","method":"GFP reporter constructs with domain deletions, live fluorescence microscopy, tracking from RBC invasion to emergence","journal":"Eukaryotic cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — systematic deletion mapping with multiple reporter constructs tracking distinct domains, coupled with live imaging of functional consequence (PVM targeting and capping)","pmids":["21498641"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"The P. berghei syntenic gene PBANKA_1003900 (which has a similar domain structure to Pfs16 but low overall sequence similarity) is expressed only in gametocytes and ookinetes. A knockout mutant of PBANKA_1003900 in P. berghei showed no defect in sexual development or ookinete formation, though a reduction in oocyst number was observed in mosquitoes.","method":"Transgenic GFP-fusion reporter, gene knockout, ookinete formation assay, mosquito transmission assay","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean knockout with phenotypic readout in a single study; the ortholog has low sequence similarity to Pfs16 so findings may not directly translate","pmids":["29307698"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"finding":"Photoaffinity labeling of a photoactivatable probe derivative of the N-[(4-hydroxychroman-4-yl)methyl]-sulphonamide compound DDD01035881 coupled with mass spectrometry identified Pfs16 as a direct binding target. Cellular thermal shift assay confirmed that the parent compound DDD01035881 stabilizes Pfs16 in lysates from activated mature gametocytes. Parasites treated with N-4HCS compounds phenocopied the targeted deletion of Pfs16 in gametocytes (by high-resolution fluorescence and electron microscopy), implicating Pfs16 as the functional target of this transmission-blocking compound class.","method":"Photoaffinity labeling, mass spectrometry, cellular thermal shift assay, fluorescence microscopy, electron microscopy, phenotypic comparison with Pfs16 knockout","journal":"Disease models & mechanisms","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — direct physical binding shown by photoaffinity labeling + MS, independently confirmed by thermal shift assay, and functional link established by phenocopy of genetic knockout","pmids":["36715290"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"Recombinant Pfs16 (insect-cell expressed) interacts directly with Anopheles gambiae midgut lysate as shown by ELISA, and microscopy demonstrated that recombinant Pfs16 binds to midgut epithelial cells. Feeding recombinant Pfs16 to mosquitoes increased oocyst numbers. Pfs16 reduced caspase 3/7 activity in mosquito midguts, implicating it in suppression of the mosquito Jun-N-terminal kinase immune pathway. Anti-Pfs16 polyclonal antibody significantly reduced oocyst numbers in mosquito midguts.","method":"ELISA binding assay with midgut lysate, fluorescence microscopy, mosquito feeding assays (recombinant protein and antibody), caspase 3/7 activity assay, structural analysis","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (ELISA, microscopy, in vivo mosquito assay, enzymatic assay) in a single lab","pmids":["37196765"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"Structural analysis identified Pfs16 as an alpha-helical integral membrane protein with one transmembrane domain connecting two regions across the parasitophorous vacuole membrane.","method":"Structural analysis (computational/modeling — abstract does not specify experimental structure method)","journal":"The Journal of biological chemistry","confidence":"Low","confidence_rationale":"Tier 4 / Weak — abstract states 'structural analysis' without specifying crystal/cryo-EM/NMR; likely computational prediction","pmids":["37196765"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"Recombinant Pfs16 (PF3D7_0406200) expressed using the baculovirus system interacts with blood-fed Anopheles gambiae midgut lysate. Knockout of the Pfs16 ortholog in P. berghei reduced oocyst numbers in mosquitoes (citing prior work). Anti-Pfs16 polyclonal antibody significantly inhibited P. falciparum transmission to Anopheles gambiae in standard membrane feeding assays.","method":"Baculovirus-expressed recombinant protein binding to midgut lysate, standard membrane feeding assay with polyclonal antibody","journal":"Frontiers in cellular and infection microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding assay plus functional transmission-blocking assay, single lab","pmids":["34262880"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1995,"finding":"Immunization with recombinant Pfs16 vaccinia virus or yeast-produced Pfs16-HBsAg hybrid particles elicited Pfs16-specific antibodies that showed no transmission-blocking activity but efficiently diminished or abolished in vitro invasion of sporozoites into human hepatoma cells (HepG2-A16) and primary human hepatocytes.","method":"Recombinant vaccinia virus expression, yeast hybrid particle production, sporozoite invasion inhibition assay (HepG2-A16 and primary hepatocytes)","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional in vitro invasion inhibition assay with two vaccine platforms; single lab but two orthogonal immunization approaches","pmids":["8538688"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"Pfs16 (PF3D7_0406200) is a 16-kDa alpha-helical integral membrane protein of the parasitophorous vacuole membrane (PVM), expressed from the earliest sexually committed ring stages through gametocytogenesis and retained in sporozoites; its C-terminal 53 amino acids are sufficient for PVM targeting and retention, a region between the signal sequence and transmembrane domain mediates 'capping' at gametocyte ends during emergence, and the gene's transcription is activated at sexual commitment and modulated post-transcriptionally; targeted disruption reduces gametocyte production and impairs exflagellation without abolishing sexual development; the protein binds Anopheles gambiae midgut epithelial cells and suppresses mosquito caspase 3/7-dependent innate immunity to facilitate parasite transmission, and it has been identified as the direct molecular target of a transmission-blocking sulphonamide compound class."},"narrative":{"mechanistic_narrative":"Pfs16 (PF3D7_0406200) is a 16-kDa, 157-amino-acid integral membrane protein of the parasitophorous vacuole membrane (PVM) that serves as one of the earliest markers of sexual commitment in Plasmodium falciparum, with expression induced immediately after invasion by sexually committed merozoites and sustained through gametocytogenesis and into macrogametes and sporozoites [PMID:7935618, PMID:2038355, PMID:9364968]. Its expression is switched on transcriptionally at the onset of gametocytogenesis via a defined promoter activated in sexually committed ring stages, with additional post-transcriptional modulation [PMID:9364968, PMID:9891033]. PVM targeting and retention are encoded by its C-terminal 53 amino acids, which carry a motif shared with other PVM proteins, while the region between the signal sequence and transmembrane domain drives 'capping'—concentration of the protein at the gametocyte ends during emergence from the PVM and red blood cell [PMID:21498641]; structurally it is an alpha-helical protein spanning the PVM through a single transmembrane domain [PMID:37196765]. Targeted disruption of Pfs16 is not lethal to sexual development but reduces gametocyte production, impairs male exflagellation, and produces a truncated mislocalized protein, establishing a role in optimal gametocyte formation [PMID:14698439]. Beyond the parasite, recombinant Pfs16 binds Anopheles gambiae midgut epithelial cells and suppresses mosquito caspase 3/7 activity to facilitate transmission, and anti-Pfs16 antibodies reduce oocyst numbers and block transmission [PMID:37196765, PMID:34262880]. Pfs16 is the direct molecular target of the transmission-blocking N-4HCS sulphonamide compound class, whose treatment phenocopies genetic knockout [PMID:36715290].","teleology":[{"year":1991,"claim":"Establishing the primary structure and stage-specificity of Pfs16 defined it as a novel sexual-stage integral membrane protein distinct from asexual antigens.","evidence":"cDNA cloning, Western blot, and immunoelectron microscopy in P. falciparum","pmids":["2038355"],"confidence":"High","gaps":["Subcellular membrane of residence not yet resolved","Function undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1994,"claim":"Localizing Pfs16 to the PVM and tracking its fate during gametogenesis established it as a bona fide PVM protein shed with the disintegrating membrane rather than a stable gamete surface antigen.","evidence":"PVM purification, immunofluorescence, and immunoelectron microscopy in P. falciparum gametocytes","pmids":["7935618","8159458"],"confidence":"High","gaps":["Molecular basis of PVM targeting not defined","Functional consequence of shedding unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1997,"claim":"Mapping the timing and regulation of Pfs16 expression showed it is induced at the moment of sexually committed invasion and controlled at both transcriptional and post-transcriptional levels, making it a marker of the commitment switch.","evidence":"Promoter-reporter transfection, Northern blot, single-cell in situ hybridization, and metabolic labeling in P. falciparum","pmids":["9364968"],"confidence":"High","gaps":["Identity of transcriptional activators unknown","Nature of post-transcriptional control unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1999,"claim":"Dissecting the pfs16 promoter identified the regulatory regions driving activation at the earliest developmental switch of sexual differentiation.","evidence":"Promoter deletion analysis with reporter constructs in P. falciparum and P. gallinaceum","pmids":["9891033"],"confidence":"High","gaps":["Trans-acting factors binding these regions not identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium gallinaceum","strain":""}]},{"year":2004,"claim":"Genetic disruption tested whether Pfs16 is essential, revealing it is dispensable for sexual development but required for optimal gametocyte production and normal exflagellation.","evidence":"Targeted gene disruption (three clones), RT-PCR, Western blot, immunofluorescence, and exflagellation assay in P. falciparum","pmids":["14698439"],"confidence":"High","gaps":["Mechanism linking Pfs16 loss to reduced gametocytemia unknown","Exflagellation defect described as preliminary"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"Co-localization with Pfpeg3/mdv1 across PVM-derived structures placed Pfs16 within the same membrane compartments as another early gametocyte protein.","evidence":"Immunoelectron microscopy and co-expression analysis in P. falciparum stage II gametocytes","pmids":["17367781"],"confidence":"Medium","gaps":["Physical interaction between the two proteins not demonstrated","Single-lab co-localization only"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"Domain mapping identified separable sequences responsible for PVM targeting/retention and for capping during emergence, defining the structural logic of Pfs16 trafficking.","evidence":"GFP reporter deletion constructs and live imaging from invasion to emergence in P. falciparum","pmids":["21498641"],"confidence":"High","gaps":["Receptors or machinery recognizing the C-terminal motif unknown","Functional purpose of capping unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Testing the P. berghei syntenic gene assessed cross-species conservation of function, showing dispensability for sexual development but a role in oocyst formation.","evidence":"GFP-fusion reporter, gene knockout, and mosquito transmission assays in P. berghei","pmids":["29307698"],"confidence":"Medium","gaps":["Ortholog has low sequence similarity so function may not translate to Pfs16","Mechanism of oocyst reduction unknown"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2023,"claim":"Identifying Pfs16 as the direct binding target of the N-4HCS sulphonamide class, with drug treatment phenocopying knockout, validated it as a druggable transmission-blocking target.","evidence":"Photoaffinity labeling with mass spectrometry, cellular thermal shift assay, and phenotypic comparison to knockout in P. falciparum","pmids":["36715290"],"confidence":"High","gaps":["Binding site on Pfs16 not localized","Molecular consequence of compound binding undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Demonstrating that recombinant Pfs16 binds mosquito midgut cells and suppresses caspase 3/7 activity extended its role from parasite biology to active modulation of mosquito innate immunity during transmission.","evidence":"ELISA and microscopy binding assays, mosquito feeding assays with recombinant protein and antibody, caspase 3/7 activity assay, and structural analysis in P. falciparum","pmids":["37196765","34262880"],"confidence":"Medium","gaps":["Midgut receptor for Pfs16 not identified","Mechanistic link between Pfs16 binding and JNK/caspase suppression not established","How a PVM protein reaches the mosquito midgut interface unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How Pfs16's intracellular PVM role connects mechanistically to its extracellular midgut binding and immune-suppressive activity, and the molecular pathway by which its loss reduces gametocyte production, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No experimental 3D structure of Pfs16","Direct binding partners within the parasite not identified","Mechanistic basis of the gametocyte-production defect unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFPEG3/MDV1 (CO-LOCALIZATION ONLY) [#6]","ANOPHELES GAMBIAE MIDGUT EPITHELIAL CELLS / MIDGUT LYSATE [#10, #12]","N-4HCS SULPHONAMIDE COMPOUND DDD01035881 (DIRECT SMALL-MOLECULE BINDER) [#9]"],"other_free_text":["Earliest known marker of sexual commitment; expression induced immediately post-invasion by sexually committed merozoites [#3, #4].","C-terminal 53 aa sufficient for PVM targeting/retention; motif shared with seven other PVM proteins [#7].","Region between signal sequence and transmembrane domain mediates 'capping' at gametocyte ends during emergence [#7].","Knockout is viable for sexual development but reduces gametocyte production and impairs exflagellation [#5].","P. berghei syntenic ortholog (PBANKA_1003900, low sequence similarity) knockout reduces oocyst number without sexual-development defect [#8].","Anti-Pfs16 antibodies block P. falciparum transmission and reduce oocysts; recombinant Pfs16 feeding increases oocysts [#10, #12].","Anti-Pfs16 antibodies inhibit sporozoite invasion of hepatocytes without transmission-blocking activity [#13]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"16879650","id":"PMC_16879650","title":"Malaria transmission-blocking antigen, Pfs230, mediates human red blood cell binding to exflagellating male parasites and oocyst production.","date":"2006","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/16879650","citation_count":144,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24206914","id":"PMC_24206914","title":"Identification of inhibitors of Plasmodium falciparum gametocyte development.","date":"2013","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/24206914","citation_count":128,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15279949","id":"PMC_15279949","title":"Quantification of Plasmodium falciparum gametocytes in differential stages of development by quantitative nucleic acid sequence-based amplification.","date":"2004","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15279949","citation_count":127,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"7935618","id":"PMC_7935618","title":"Cellular location and temporal expression of the Plasmodium falciparum sexual stage antigen Pfs16.","date":"1994","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/7935618","citation_count":95,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"9891033","id":"PMC_9891033","title":"Isolation and functional characterization of two distinct sexual-stage-specific promoters of the human malaria parasite Plasmodium falciparum.","date":"1999","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/9891033","citation_count":82,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15996767","id":"PMC_15996767","title":"Identification of a subtelomeric gene family expressed during the asexual-sexual stage transition in Plasmodium falciparum.","date":"2005","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15996767","citation_count":77,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19703460","id":"PMC_19703460","title":"Anopheles dirus co-infection with human and monkey malaria parasites in Vietnam.","date":"2009","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/19703460","citation_count":57,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"2038355","id":"PMC_2038355","title":"A novel protein antigen of the malaria parasite Plasmodium falciparum, located on the surface of gametes and sporozoites.","date":"1991","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/2038355","citation_count":54,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25102353","id":"PMC_25102353","title":"Multicolor bioluminescence boosts malaria research: quantitative dual-color assay and single-cell imaging in Plasmodium falciparum parasites.","date":"2014","source":"Analytical chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25102353","citation_count":52,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"7891740","id":"PMC_7891740","title":"Expression of early gametocyte-stage antigens Pfg27 and Pfs16 in synchronized gametocytes and non-gametocyte producing clones of Plasmodium falciparum.","date":"1994","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/7891740","citation_count":51,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"8159458","id":"PMC_8159458","title":"Subcellular localization of Pfs16, a Plasmodium falciparum gametocyte antigen.","date":"1994","source":"Parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/8159458","citation_count":49,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"9364968","id":"PMC_9364968","title":"Developmentally regulated expression of pfs16, a marker for sexual differentiation of the human malaria parasite Plasmodium falciparum.","date":"1997","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/9364968","citation_count":45,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20542143","id":"PMC_20542143","title":"Development of a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) for clinical detection of Plasmodium falciparum gametocytes.","date":"2010","source":"Parasitology international","url":"https://pubmed.ncbi.nlm.nih.gov/20542143","citation_count":43,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"14698439","id":"PMC_14698439","title":"Functional analysis of Plasmodium falciparum parasitophorous vacuole membrane protein (Pfs16) during gametocytogenesis and gametogenesis by targeted gene disruption.","date":"2004","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/14698439","citation_count":41,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"17367781","id":"PMC_17367781","title":"Plasmodium falciparum: mRNA co-expression and protein co-localisation of two gene products upregulated in early gametocytes.","date":"2007","source":"Experimental parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/17367781","citation_count":41,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28416533","id":"PMC_28416533","title":"Capturing in vivo RNA transcriptional dynamics from the malaria parasite Plasmodium falciparum.","date":"2017","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/28416533","citation_count":40,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"12067340","id":"PMC_12067340","title":"Targeting and sequestration of truncated Pfs230 in an intraerythrocytic compartment during Plasmodium falciparum gametocytogenesis.","date":"2002","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/12067340","citation_count":39,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19027798","id":"PMC_19027798","title":"A green fluorescent protein-based assay for determining gametocyte production in Plasmodium falciparum.","date":"2008","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/19027798","citation_count":35,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"11425169","id":"PMC_11425169","title":"Limited polymorphism in Plasmodium falciparum sexual-stage antigens.","date":"2001","source":"The American journal of tropical medicine and hygiene","url":"https://pubmed.ncbi.nlm.nih.gov/11425169","citation_count":34,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26149860","id":"PMC_26149860","title":"Genome-Scale Protein Microarray Comparison of Human Antibody Responses in Plasmodium vivax Relapse and Reinfection.","date":"2015","source":"The American journal of tropical medicine and hygiene","url":"https://pubmed.ncbi.nlm.nih.gov/26149860","citation_count":28,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["S16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"10964643","id":"PMC_10964643","title":"Plasmodium falciparum: expression of gametocyte-specific genes in monolayer cultures and malaria-positive blood samples.","date":"2000","source":"Experimental parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/10964643","citation_count":25,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21498641","id":"PMC_21498641","title":"Protein targeting to the parasitophorous vacuole membrane of Plasmodium falciparum.","date":"2011","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/21498641","citation_count":24,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26283330","id":"PMC_26283330","title":"Plasmodium falciparum Gametocyte-Specific Antibody Profiling Reveals Boosting through Natural Infection and Identifies Potential Markers of Gametocyte Exposure.","date":"2015","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/26283330","citation_count":22,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31022294","id":"PMC_31022294","title":"Demographical, hematological and serological risk factors for Plasmodium falciparum gametocyte carriage in a high stable transmission zone in Cameroon.","date":"2019","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/31022294","citation_count":20,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34262880","id":"PMC_34262880","title":"Studies of the Parasite-Midgut Interaction Reveal Plasmodium Proteins Important for Malaria Transmission to Mosquitoes.","date":"2021","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/34262880","citation_count":15,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36409095","id":"PMC_36409095","title":"Plasmodium falciparum Sexual Commitment Rate Variation among Clinical Isolates and Diverse Laboratory-Adapted Lines.","date":"2022","source":"Microbiology spectrum","url":"https://pubmed.ncbi.nlm.nih.gov/36409095","citation_count":15,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24528780","id":"PMC_24528780","title":"A rapid sensitive, flow cytometry-based method for the detection of Plasmodium vivax-infected blood cells.","date":"2014","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/24528780","citation_count":15,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PvS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"1922202","id":"PMC_1922202","title":"Minimal variation in Pfs16, a novel protein located in the membrane of gametes and sporozoites of Plasmodium falciparum.","date":"1991","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/1922202","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"8538688","id":"PMC_8538688","title":"Induction of Plasmodium falciparum sporozoite-neutralizing antibodies upon vaccination with recombinant Pfs16 vaccinia virus and/or recombinant Pfs16 protein produced in yeast.","date":"1995","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/8538688","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23607486","id":"PMC_23607486","title":"Temporal evaluation of commitment to sexual development in Plasmodium falciparum.","date":"2013","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/23607486","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36715290","id":"PMC_36715290","title":"A novel class of sulphonamides potently block malaria transmission by targeting a Plasmodium vacuole membrane protein.","date":"2023","source":"Disease models & mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/36715290","citation_count":11,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24305630","id":"PMC_24305630","title":"Evaluation of Plasmodium falciparum gametocyte detection in different patient material.","date":"2013","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/24305630","citation_count":11,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30995911","id":"PMC_30995911","title":"Hospital-derived antibody profiles of malaria patients in Southwest India.","date":"2019","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/30995911","citation_count":11,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["S16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"9184918","id":"PMC_9184918","title":"Recombinant vaccinia viruses for the characterization of Plasmodium falciparum-specific cytotoxic T lymphocytes: recognition of processed antigen despite limited re-stimulation efficacy.","date":"1997","source":"International immunology","url":"https://pubmed.ncbi.nlm.nih.gov/9184918","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33568138","id":"PMC_33568138","title":"Phagocytosis and activation of bone marrow-derived macrophages by Plasmodium falciparum gametocytes.","date":"2021","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/33568138","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35096643","id":"PMC_35096643","title":"Gene Polymorphisms Among Plasmodium vivax Geographical Isolates and the Potential as New Biomarkers for Gametocyte Detection.","date":"2022","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/35096643","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PvS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37196765","id":"PMC_37196765","title":"Plasmodium parasitophorous vacuole membrane protein Pfs16 promotes malaria transmission by silencing mosquito immunity.","date":"2023","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/37196765","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30305101","id":"PMC_30305101","title":"Dynamics of Plasmodium falciparum gametocyte carriage in pregnant women under intermittent preventive treatment with sulfadoxine-pyrimethamine in Benin.","date":"2018","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/30305101","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"9226690","id":"PMC_9226690","title":"Humoral immune responses in Gambians to Pfs16, an immunodominant, Plasmodium falciparum integral membrane protein.","date":"1996","source":"Parasite immunology","url":"https://pubmed.ncbi.nlm.nih.gov/9226690","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32425505","id":"PMC_32425505","title":"In vitro Multistage Malaria Transmission Blocking Activity of Selected Malaria Box Compounds.","date":"2020","source":"Drug design, development and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/32425505","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"1741021","id":"PMC_1741021","title":"Sequence of a 16-kilodalton sexual stage and sporozoite surface antigen of Plasmodium reichenowi and comparison with Pfs16 of Plasmodium falciparum.","date":"1992","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/1741021","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"29307698","id":"PMC_29307698","title":"Sequence and functional divergence of gametocyte-specific parasitophorous vacuole membrane proteins in Plasmodium parasites.","date":"2018","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/29307698","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39710726","id":"PMC_39710726","title":"Multi-locus investigation of Anopheles-mediated selective pressure on Plasmodium falciparum in Africa.","date":"2024","source":"Parasites & vectors","url":"https://pubmed.ncbi.nlm.nih.gov/39710726","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32014000","id":"PMC_32014000","title":"Sexual forms obtained in a continuous in vitro cultured Colombian strain of Plasmodium falciparum (FCB2).","date":"2020","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/32014000","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31234875","id":"PMC_31234875","title":"Signatures of divergent anti-malarial treatment responses in peripheral blood from adults and young children in Malawi.","date":"2019","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/31234875","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40672192","id":"PMC_40672192","title":"Navigating parasite antigen genetic diversity in the design of Plasmodium vivax serological exposure markers for malaria.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40672192","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["S16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42155491","id":"PMC_42155491","title":"Assessing the effect of parasite antigen genetic diversity on performance of Plasmodium vivax serological exposure markers for malaria: a multicentre observational diagnostic accuracy study.","date":"2026","source":"The Lancet. Microbe","url":"https://pubmed.ncbi.nlm.nih.gov/42155491","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["S16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39979562","id":"PMC_39979562","title":"Pfs16: A Key Parasitophorous Vacuole Membrane Protein Crucial for Malaria Parasite Development and Transmission.","date":"2025","source":"The protein journal","url":"https://pubmed.ncbi.nlm.nih.gov/39979562","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39574894","id":"PMC_39574894","title":"Multi-locus investigation of Anopheles-mediated selective pressure on Plasmodium falciparum in Africa.","date":"2024","source":"Research square","url":"https://pubmed.ncbi.nlm.nih.gov/39574894","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42294623","id":"PMC_42294623","title":"Plasmodium falciparum leucine-rich repeat 5 disruption alters the transcription progression during asexual and sexual stage development.","date":"2026","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/42294623","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42684939","id":"PMC_42684939","title":"Persistence of Plasmodium falciparum DNA detection after antimalarial treatment and the implication of gametocytes: a prospective cohort study in a non-endemic setting.","date":"2026","source":"Microbiology spectrum","url":"https://pubmed.ncbi.nlm.nih.gov/42684939","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["Pfs16","PfS16"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":28568,"output_tokens":4196,"usd":0.074322,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10521,"output_tokens":4022,"usd":0.076578,"stage2_stop_reason":"end_turn"},"total_usd":0.1509,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1994,\n      \"finding\": \"Pfs16 is localized to the parasitophorous vacuole membrane (PVM) of P. falciparum gametocytes. Purification of PVMs from mature and immature gametocytes combined with immunoelectron microscopy established this localization. During gametogenesis, the PVM is shed along with the RBC membrane, and Pfs16 is retained on the disintegrating membrane; in a minority of cases, Pfs16 can be retained on the gamete surface. First expression was estimated at 35 hours post-merozoite invasion in sexually committed ring stages.\",\n      \"method\": \"Immunofluorescence assay, immunoelectron microscopy, PVM purification from gametocytes\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct subcellular fractionation (PVM purification) combined with immunoelectron microscopy, replicated by subsequent independent studies\",\n      \"pmids\": [\"7935618\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"Pfs16 is localized specifically to the parasitophorous vacuole membrane (PVM) in gametocytes, and during gametogenesis when the PVM disintegrates, the antigen is detected on multilaminated whorls (remains of the PVM) and not on the gamete plasma membrane. Pfs16 is also present on membranes surrounding cytosomes and food vacuoles within the parasite cytoplasm, and on structures believed to be Garnham bodies in the host cell cytoplasm.\",\n      \"method\": \"Immunoelectron microscopy\",\n      \"journal\": \"Parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — immunoelectron microscopy with precise subcellular resolution, independently corroborated by PMID:7935618\",\n      \"pmids\": [\"8159458\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1991,\n      \"finding\": \"Pfs16 encodes a 157-amino-acid, 16-kDa integral membrane protein with a putative N-terminal signal sequence, a hydrophobic membrane anchor, and a highly hydrophilic C-terminal region. The protein is expressed on the surface of macrogametes and sporozoites but not in asexual erythrocytic stages, as demonstrated by immunofluorescence and immunoelectron microscopy with protein A-gold.\",\n      \"method\": \"cDNA cloning, Western blot, immunofluorescence assay, immunoelectron microscopy (protein A-gold)\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (molecular cloning, Western blot, IEM) in a single study; independently replicated\",\n      \"pmids\": [\"2038355\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"Expression of Pfs16 is induced immediately following invasion of a red blood cell by sexually committed merozoites and continues throughout gametocytogenesis and in macrogametes. Regulation is at the level of transcription initiation and is also modulated by a post-transcriptional process, as shown by comparative analysis of promoter activity, RNA levels (in situ hybridization at single-cell level), and de novo protein synthesis rates.\",\n      \"method\": \"Promoter-reporter transfection assay, Northern blot, in situ hybridization, metabolic labeling of de novo protein synthesis\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (promoter activity, RNA quantification, single-cell ISH, metabolic labeling) in one study\",\n      \"pmids\": [\"9364968\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"The pfs16 promoter is activated at the onset of gametocytogenesis (in sexually committed ring-stage parasites), marking the earliest developmental switch in sexual differentiation. The regions of the pfs16 promoter essential for high transcriptional activity were identified by deletion analysis using transfection of P. falciparum and P. gallinaceum.\",\n      \"method\": \"Promoter deletion analysis, P. falciparum and P. gallinaceum transfection with reporter constructs\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — functional promoter dissection in two Plasmodium species with reporter assays, multiple constructs tested\",\n      \"pmids\": [\"9891033\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}, {\"species\": \"Plasmodium gallinaceum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Targeted disruption of the Pfs16 gene by homologous recombination (three independent clones confirmed) resulted in: (1) absence of full-length Pfs16 transcripts and PVM-localized 16 kDa protein; (2) expression of a 14 kDa truncated protein mislocalized to an unidentified double-membrane compartment; (3) significant reduction in gametocyte production; (4) preliminary evidence of impaired male gametocyte exflagellation in vitro. Pfs16 is not essential for sexual development but is required for optimal gametocyte production.\",\n      \"method\": \"Targeted gene disruption by homologous recombination, RT-PCR, Western blot, immunofluorescence, exflagellation assay\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — three independent knockout clones confirmed by Southern blot and molecular analysis, multiple orthogonal readouts\",\n      \"pmids\": [\"14698439\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Pfs16 and Pfpeg3/mdv1 proteins co-localize in the PVM and in all derived membranous structures of stage II gametocytes, including multi-laminate membrane whorls of circular clefts in the erythrocyte cytoplasm, membranes of food vacuoles, and distinct cleft-like structures in the erythrocyte cytoplasm, as shown by immunoelectron microscopy.\",\n      \"method\": \"Immunoelectron microscopy, immunofluorescence, co-expression analysis\",\n      \"journal\": \"Experimental parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — immunoelectron microscopy co-localization, single lab, but orthogonal to prior PVM localization findings\",\n      \"pmids\": [\"17367781\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"The 53 C-terminal amino acids of Pfs16 (appended to a GFP reporter already containing the N-terminal secretory signal) are sufficient for targeting to and retention on the PVM. Removal of the 11 C-terminal amino acids did not prevent PVM targeting but reduced membrane retention. A sequence motif identified in the C-terminal targeting region is shared with seven other known PVM proteins. Additionally, the region between the N-terminal signal sequence and the transmembrane domain (not required for PVM targeting) was found to be involved in 'capping'—concentration of native Pfs16 and full-length Pfs16-GFP at the ends of the gametocyte during emergence from the PVM and RBC.\",\n      \"method\": \"GFP reporter constructs with domain deletions, live fluorescence microscopy, tracking from RBC invasion to emergence\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — systematic deletion mapping with multiple reporter constructs tracking distinct domains, coupled with live imaging of functional consequence (PVM targeting and capping)\",\n      \"pmids\": [\"21498641\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"The P. berghei syntenic gene PBANKA_1003900 (which has a similar domain structure to Pfs16 but low overall sequence similarity) is expressed only in gametocytes and ookinetes. A knockout mutant of PBANKA_1003900 in P. berghei showed no defect in sexual development or ookinete formation, though a reduction in oocyst number was observed in mosquitoes.\",\n      \"method\": \"Transgenic GFP-fusion reporter, gene knockout, ookinete formation assay, mosquito transmission assay\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean knockout with phenotypic readout in a single study; the ortholog has low sequence similarity to Pfs16 so findings may not directly translate\",\n      \"pmids\": [\"29307698\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Photoaffinity labeling of a photoactivatable probe derivative of the N-[(4-hydroxychroman-4-yl)methyl]-sulphonamide compound DDD01035881 coupled with mass spectrometry identified Pfs16 as a direct binding target. Cellular thermal shift assay confirmed that the parent compound DDD01035881 stabilizes Pfs16 in lysates from activated mature gametocytes. Parasites treated with N-4HCS compounds phenocopied the targeted deletion of Pfs16 in gametocytes (by high-resolution fluorescence and electron microscopy), implicating Pfs16 as the functional target of this transmission-blocking compound class.\",\n      \"method\": \"Photoaffinity labeling, mass spectrometry, cellular thermal shift assay, fluorescence microscopy, electron microscopy, phenotypic comparison with Pfs16 knockout\",\n      \"journal\": \"Disease models & mechanisms\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — direct physical binding shown by photoaffinity labeling + MS, independently confirmed by thermal shift assay, and functional link established by phenocopy of genetic knockout\",\n      \"pmids\": [\"36715290\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Recombinant Pfs16 (insect-cell expressed) interacts directly with Anopheles gambiae midgut lysate as shown by ELISA, and microscopy demonstrated that recombinant Pfs16 binds to midgut epithelial cells. Feeding recombinant Pfs16 to mosquitoes increased oocyst numbers. Pfs16 reduced caspase 3/7 activity in mosquito midguts, implicating it in suppression of the mosquito Jun-N-terminal kinase immune pathway. Anti-Pfs16 polyclonal antibody significantly reduced oocyst numbers in mosquito midguts.\",\n      \"method\": \"ELISA binding assay with midgut lysate, fluorescence microscopy, mosquito feeding assays (recombinant protein and antibody), caspase 3/7 activity assay, structural analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (ELISA, microscopy, in vivo mosquito assay, enzymatic assay) in a single lab\",\n      \"pmids\": [\"37196765\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Structural analysis identified Pfs16 as an alpha-helical integral membrane protein with one transmembrane domain connecting two regions across the parasitophorous vacuole membrane.\",\n      \"method\": \"Structural analysis (computational/modeling — abstract does not specify experimental structure method)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — abstract states 'structural analysis' without specifying crystal/cryo-EM/NMR; likely computational prediction\",\n      \"pmids\": [\"37196765\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Recombinant Pfs16 (PF3D7_0406200) expressed using the baculovirus system interacts with blood-fed Anopheles gambiae midgut lysate. Knockout of the Pfs16 ortholog in P. berghei reduced oocyst numbers in mosquitoes (citing prior work). Anti-Pfs16 polyclonal antibody significantly inhibited P. falciparum transmission to Anopheles gambiae in standard membrane feeding assays.\",\n      \"method\": \"Baculovirus-expressed recombinant protein binding to midgut lysate, standard membrane feeding assay with polyclonal antibody\",\n      \"journal\": \"Frontiers in cellular and infection microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding assay plus functional transmission-blocking assay, single lab\",\n      \"pmids\": [\"34262880\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"Immunization with recombinant Pfs16 vaccinia virus or yeast-produced Pfs16-HBsAg hybrid particles elicited Pfs16-specific antibodies that showed no transmission-blocking activity but efficiently diminished or abolished in vitro invasion of sporozoites into human hepatoma cells (HepG2-A16) and primary human hepatocytes.\",\n      \"method\": \"Recombinant vaccinia virus expression, yeast hybrid particle production, sporozoite invasion inhibition assay (HepG2-A16 and primary hepatocytes)\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional in vitro invasion inhibition assay with two vaccine platforms; single lab but two orthogonal immunization approaches\",\n      \"pmids\": [\"8538688\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"Pfs16 (PF3D7_0406200) is a 16-kDa alpha-helical integral membrane protein of the parasitophorous vacuole membrane (PVM), expressed from the earliest sexually committed ring stages through gametocytogenesis and retained in sporozoites; its C-terminal 53 amino acids are sufficient for PVM targeting and retention, a region between the signal sequence and transmembrane domain mediates 'capping' at gametocyte ends during emergence, and the gene's transcription is activated at sexual commitment and modulated post-transcriptionally; targeted disruption reduces gametocyte production and impairs exflagellation without abolishing sexual development; the protein binds Anopheles gambiae midgut epithelial cells and suppresses mosquito caspase 3/7-dependent innate immunity to facilitate parasite transmission, and it has been identified as the direct molecular target of a transmission-blocking sulphonamide compound class.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"Pfs16 (PF3D7_0406200) is a 16-kDa, 157-amino-acid integral membrane protein of the parasitophorous vacuole membrane (PVM) that serves as one of the earliest markers of sexual commitment in Plasmodium falciparum, with expression induced immediately after invasion by sexually committed merozoites and sustained through gametocytogenesis and into macrogametes and sporozoites [#0, #2, #3]. Its expression is switched on transcriptionally at the onset of gametocytogenesis via a defined promoter activated in sexually committed ring stages, with additional post-transcriptional modulation [#3, #4]. PVM targeting and retention are encoded by its C-terminal 53 amino acids, which carry a motif shared with other PVM proteins, while the region between the signal sequence and transmembrane domain drives 'capping'—concentration of the protein at the gametocyte ends during emergence from the PVM and red blood cell [#7]; structurally it is an alpha-helical protein spanning the PVM through a single transmembrane domain [#11]. Targeted disruption of Pfs16 is not lethal to sexual development but reduces gametocyte production, impairs male exflagellation, and produces a truncated mislocalized protein, establishing a role in optimal gametocyte formation [#5]. Beyond the parasite, recombinant Pfs16 binds Anopheles gambiae midgut epithelial cells and suppresses mosquito caspase 3/7 activity to facilitate transmission, and anti-Pfs16 antibodies reduce oocyst numbers and block transmission [#10, #12]. Pfs16 is the direct molecular target of the transmission-blocking N-4HCS sulphonamide compound class, whose treatment phenocopies genetic knockout [#9].\",\n  \"teleology\": [\n    {\n      \"year\": 1991,\n      \"claim\": \"Establishing the primary structure and stage-specificity of Pfs16 defined it as a novel sexual-stage integral membrane protein distinct from asexual antigens.\",\n      \"evidence\": \"cDNA cloning, Western blot, and immunoelectron microscopy in P. falciparum\",\n      \"pmids\": [\"2038355\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Subcellular membrane of residence not yet resolved\", \"Function undefined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1994,\n      \"claim\": \"Localizing Pfs16 to the PVM and tracking its fate during gametogenesis established it as a bona fide PVM protein shed with the disintegrating membrane rather than a stable gamete surface antigen.\",\n      \"evidence\": \"PVM purification, immunofluorescence, and immunoelectron microscopy in P. falciparum gametocytes\",\n      \"pmids\": [\"7935618\", \"8159458\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of PVM targeting not defined\", \"Functional consequence of shedding unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Mapping the timing and regulation of Pfs16 expression showed it is induced at the moment of sexually committed invasion and controlled at both transcriptional and post-transcriptional levels, making it a marker of the commitment switch.\",\n      \"evidence\": \"Promoter-reporter transfection, Northern blot, single-cell in situ hybridization, and metabolic labeling in P. falciparum\",\n      \"pmids\": [\"9364968\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity of transcriptional activators unknown\", \"Nature of post-transcriptional control unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Dissecting the pfs16 promoter identified the regulatory regions driving activation at the earliest developmental switch of sexual differentiation.\",\n      \"evidence\": \"Promoter deletion analysis with reporter constructs in P. falciparum and P. gallinaceum\",\n      \"pmids\": [\"9891033\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Trans-acting factors binding these regions not identified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}, {\"species\": \"Plasmodium gallinaceum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Genetic disruption tested whether Pfs16 is essential, revealing it is dispensable for sexual development but required for optimal gametocyte production and normal exflagellation.\",\n      \"evidence\": \"Targeted gene disruption (three clones), RT-PCR, Western blot, immunofluorescence, and exflagellation assay in P. falciparum\",\n      \"pmids\": [\"14698439\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism linking Pfs16 loss to reduced gametocytemia unknown\", \"Exflagellation defect described as preliminary\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Co-localization with Pfpeg3/mdv1 across PVM-derived structures placed Pfs16 within the same membrane compartments as another early gametocyte protein.\",\n      \"evidence\": \"Immunoelectron microscopy and co-expression analysis in P. falciparum stage II gametocytes\",\n      \"pmids\": [\"17367781\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physical interaction between the two proteins not demonstrated\", \"Single-lab co-localization only\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Domain mapping identified separable sequences responsible for PVM targeting/retention and for capping during emergence, defining the structural logic of Pfs16 trafficking.\",\n      \"evidence\": \"GFP reporter deletion constructs and live imaging from invasion to emergence in P. falciparum\",\n      \"pmids\": [\"21498641\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Receptors or machinery recognizing the C-terminal motif unknown\", \"Functional purpose of capping unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Testing the P. berghei syntenic gene assessed cross-species conservation of function, showing dispensability for sexual development but a role in oocyst formation.\",\n      \"evidence\": \"GFP-fusion reporter, gene knockout, and mosquito transmission assays in P. berghei\",\n      \"pmids\": [\"29307698\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Ortholog has low sequence similarity so function may not translate to Pfs16\", \"Mechanism of oocyst reduction unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identifying Pfs16 as the direct binding target of the N-4HCS sulphonamide class, with drug treatment phenocopying knockout, validated it as a druggable transmission-blocking target.\",\n      \"evidence\": \"Photoaffinity labeling with mass spectrometry, cellular thermal shift assay, and phenotypic comparison to knockout in P. falciparum\",\n      \"pmids\": [\"36715290\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Binding site on Pfs16 not localized\", \"Molecular consequence of compound binding undefined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Demonstrating that recombinant Pfs16 binds mosquito midgut cells and suppresses caspase 3/7 activity extended its role from parasite biology to active modulation of mosquito innate immunity during transmission.\",\n      \"evidence\": \"ELISA and microscopy binding assays, mosquito feeding assays with recombinant protein and antibody, caspase 3/7 activity assay, and structural analysis in P. falciparum\",\n      \"pmids\": [\"37196765\", \"34262880\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Midgut receptor for Pfs16 not identified\", \"Mechanistic link between Pfs16 binding and JNK/caspase suppression not established\", \"How a PVM protein reaches the mosquito midgut interface unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How Pfs16's intracellular PVM role connects mechanistically to its extracellular midgut binding and immune-suppressive activity, and the molecular pathway by which its loss reduces gametocyte production, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No experimental 3D structure of Pfs16\", \"Direct binding partners within the parasite not identified\", \"Mechanistic basis of the gametocyte-production defect unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [10, 12]},\n      {\"term_id\": \"GO:0002862\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020005\", \"supporting_discovery_ids\": [0, 1, 2, 6, 7, 11]},\n      {\"term_id\": \"GO:0016021\", \"supporting_discovery_ids\": [2, 11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0030437\", \"supporting_discovery_ids\": [3, 4, 5]},\n      {\"term_id\": \"GO:0048240\", \"supporting_discovery_ids\": [10, 12]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"Pfpeg3/mdv1 (co-localization only) [#6]\",\n      \"Anopheles gambiae midgut epithelial cells / midgut lysate [#10, #12]\",\n      \"N-4HCS sulphonamide compound DDD01035881 (direct small-molecule binder) [#9]\"\n    ],\n    \"other_free_text\": [\n      \"Earliest known marker of sexual commitment; expression induced immediately post-invasion by sexually committed merozoites [#3, #4].\",\n      \"C-terminal 53 aa sufficient for PVM targeting/retention; motif shared with seven other PVM proteins [#7].\",\n      \"Region between signal sequence and transmembrane domain mediates 'capping' at gametocyte ends during emergence [#7].\",\n      \"Knockout is viable for sexual development but reduces gametocyte production and impairs exflagellation [#5].\",\n      \"P. berghei syntenic ortholog (PBANKA_1003900, low sequence similarity) knockout reduces oocyst number without sexual-development defect [#8].\",\n      \"Anti-Pfs16 antibodies block P. falciparum transmission and reduce oocysts; recombinant Pfs16 feeding increases oocysts [#10, #12].\",\n      \"Anti-Pfs16 antibodies inhibit sporozoite invasion of hepatocytes without transmission-blocking activity [#13].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0406200","name":null,"product":"parasitophorous vacuole membrane protein S16","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0304300","name":null,"product":"parasitophorous vacuole membrane protein S16, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"Pfs16","evaluation":null}