ROM10

ROM10 (PF3D7_0618600) is a rhomboid intramembrane protease family member whose loss-of-function studies indicate it is dispensable for parasite life cycle progression: systematic gene deletion in P. berghei produced parasites with no major defects across blood, mosquito, and liver stages under standard laboratory conditions (PMID:23490234). In P. falciparum, N-terminal 3xHA tagging of ROM10 is deleterious and blocks recovery of drug-resistant parasites, so that inducible knockout was achievable only with constructs lacking the N-terminal tag, establishing that the N-terminal region is functionally important (PMID:39739757). In P. berghei gametocytes, the ROM10 transcript associates with the translational repressors DOZI and CITH, placing it within the maternal repressome and indicating the mRNA is stored in a translationally repressed state for post-fertilization use (PMID:25418785). Beyond these observations, no substrate, catalytic activity, subcellular localization, or interacting protease complex has been characterized for ROM10 itself in the available corpus.

1. 2013 Medium

   To ask whether ROM10 is required for parasite survival, its gene was deleted and the resulting parasites were assessed across the life cycle, establishing that ROM10 is not essential under laboratory conditions.

   Evidence Systematic reverse-genetics gene deletion with phenotypic assessment across blood, mosquito, and liver stages in P. berghei

   PMID:23490234

   Open questions at the time

   • Dispensability under standard conditions does not exclude a stage-specific or stress-conditional role
   • No substrate, catalytic activity, or localization determined
   • Findings in P. berghei may not transfer to P. falciparum
2. 2014 Low

   To understand how ROM10 expression is timed, its transcript was tested for association with maternal repressors, showing it is stored translationally repressed in gametocytes for later developmental deployment.

   Evidence RIP-Chip using DOZI and CITH as bait in P. berghei gametocytes

   PMID:25418785

   Open questions at the time

   • Single RIP experiment without functional validation of ROM10 protein activity
   • Timing and trigger of translational de-repression not defined
   • Does not establish what ROM10 protein does post-fertilization
3. 2025 Low

   To probe the functional importance of ROM10's N-terminus, tagging and inducible knockout were attempted, revealing that N-terminal modification impairs ROM10 function.

   Evidence SHIFTiKO inducible knockout with DiCre-lox and N-terminal 3xHA tag constructs in P. falciparum; failure to recover parasites carrying the N-terminal tag

   PMID:39739757

   Open questions at the time

   • Inference rests on failure to recover tagged parasites, an indirect readout without mechanistic follow-up
   • Why the N-terminus is required (folding, localization, catalysis) is unresolved
   • No direct assay of ROM10 protease activity

• The catalytic substrate, protease activity, subcellular localization, and physiological role of ROM10 itself remain undefined.
• No substrate identified for ROM10
• No demonstration of intramembrane protease activity for ROM10 specifically
• No localization or interacting-complex data for ROM10