Function knowledge gaps

Curating what biology does not know about a gene, with sources

AI Gene Review · projects/FUNCTION_KNOWLEDGE_GAPS · 2026

Bottom line

  • About a fifth of proteins in well-studied organisms still have no informative description; we record each unknown as a sourced, curated statement.
  • A darkness metric failed: most flagged genes were structural subunits or curation gaps. A gap is now a judgement made by reading.
  • KnowledgeGap is a schema class; the YAMLs now hold 1,461 gaps in 535 gene and module files.

Why: the unknome

  • Wood et al. 2019: ~20% of proteins in well-studied organisms lack an informative role; many are conserved yeast → human.
  • Unknome database (Rocha et al. 2023): 23% of human clusters still "unknown"; of 260 conserved-unknown fly genes, 62 were essential.
  • Genes stay dark for sociological reasons (the streetlight effect).
  • A funder trying to close the unknome would first need an honest map of the real gaps.

A metric can't find gaps

Taxonomy

Kind Meaning Who fixes it Exemplar
Biology nobody knows experiment CFAP300, tam10, P3R3URF
Curation known, not annotated curator MAP7D1, AP3B2
Ontology known, no GO term for it GO editors POLE4
Contested two incompatible experimental answers both TMEM65, TMEM175
Residual sub-gap one sharp hole in a solved gene experiment RAB9A, RASA1, atg101

Anatomy of a gap

The register today

Lessons from curating 23 worked entries

  • Deep-research files invent citations: KCTD14 and AP3B2 summaries cited PMIDs that resolve to unrelated papers; RASA1's "tandem-SH2" PMID was a stem-cell paper.
  • So provenance must be a verified primary source or a checkable repo fact (GOA evidence codes).
  • file: quotes are not verbatim-checked; prefer PMID quotes.
  • Contested gaps are often already in GOA, with experimental codes on both sides.

Status and next steps

  • ✅ Taxonomy, schema class, 23 worked entries, contested-function survey.
  • ✅ Register generator: just aggregate-knowledge-gaps → structured-gaps.md (last run lists 1,073; YAMLs now hold 1,461).
  • ⬜ validate-deep-research: PMID resolution + title match.
  • ⬜ Read-list batch 4 (PUS3, CFAP418, SOCS4/5, RFT1, pef-1, fshr-1, alo1).
  • ⬜ Curate contested candidates: TMEM175; TMEM65 + SLC8B1; MEFV.

Read more: projects/FUNCTION_KNOWLEDGE_GAPS.md