FANCF (FANCF) — AIGR vs Affinage
Affinage record: run 2026-06-09 · 9 discoveries · self-eval pairwise = win, faith 100% · gates passed.
Agreement (brief)
Affinage and the AIGR review agree on the core biology: FANCF is a nuclear subunit of
the Fanconi anemia (FA) core complex that drives FANCD2 monoubiquitination to enable
DNA interstrand cross-link (ICL) repair, and its molecular role is a flexible molecular
adaptor that bridges the FANCA:FANCG and FANCC:FANCE subcomplexes. Both cite the same
primary structural/interaction papers (PMID:11063725 nuclear core-complex membership;
PMID:15262960 flexible adaptor; PMID:17082180 Cand1-like C-terminal fold + adaptor surface).
Affinage's narrative molecular_activity (GO:0060090 molecular adaptor activity) and
localization (GO:0005634 nucleus) match the AIGR core_functions and localization calls.
Disagreements
| Topic | Affinage says | AIGR review says | Verdict (who is right + why) |
|---|---|---|---|
| GO grounding depth | Coarse mechanism_profile: adaptor activity / nucleus / "DNA Repair" + "Reproduction" (Reactome) |
Granular: GO:0060090 adaptor activity, GO:0043240 FA nuclear complex, GO:0036297 ICL repair, GO:0000785 chromatin, GO:0005654 nucleoplasm | AIGR. Affinage's own note concedes the profile collapses to general parents; AIGR re-grounds to specific, correctly-branched terms. Nucleus is retained but the more granular nucleoplasm/chromatin are added. |
| "Reproduction" as a FANCF function | Lists Reactome R-HSA-1474165 Reproduction as a pathway; cites Fancf-KO gonadal/ovarian-tumour phenotype (PMID:21915857) | Not annotated as a FANCF process | AIGR. Impaired gametogenesis/ovarian tumours in KO mice are downstream organismal consequences of genome instability, not a distinct molecular/cellular function of FANCF. The paper is incorporated as in-vivo support for the DNA-damage/ICL role, not as a reproduction annotation. |
| Transcriptional regulation of FANCF (IRF8/ICSBP up; p53→miR-30c down) | Presents PMID:19801548 and PMID:31511498 as FANCF findings | Not annotated | AIGR. These describe regulation of the FANCF gene (and chemoresistance consequences), not functions of the FANCF protein; annotating them to FANCF would be a category error. Correctly excluded. |
| Cancer chemoresistance / p38-JNK MAPK | PMID:22952942, PMID:23440494: FANCF silencing sensitizes tumour cells via p38/JNK | Not annotated | AIGR. Silencing-phenotype/pathway-crosstalk observations, not evidence FANCF enables MAPK signaling. Excluding these avoids over-annotation. |
| Plant / meiotic anti-crossover role | PMID:36652992: conserved FANCC-FANCE-FANCF subcomplex is an anti-crossover factor in Arabidopsis meiosis | Not annotated for human FANCF | AIGR. The meiotic anti-crossover activity is demonstrated in Arabidopsis; extrapolating a meiotic-recombination process term to human FANCF from a plant assay is not warranted. Conservatively excluded (subcomplex conservation is noted, but no human annotation). |
Papers incorporated into the review
| PMID | Supports | How used |
|---|---|---|
| PMID:15262960 | Flexible-adaptor role bridging FANCA:FANCG and FANCC:FANCE subcomplexes (core molecular function) | Added to references (relevance HIGH, VERIFIED) with verbatim supporting_text; attached as supported_by to core_functions (adaptor activity) and to the first GO:0005515→GO:0060090 MODIFY annotation. This is the primary experimental source for the adaptor model the review already asserted. |
| PMID:21915857 | In-vivo requirement of FANCF for FANCD2 monoubiquitination and the DNA cross-link damage response | Added to references (relevance MEDIUM — mouse, VERIFIED); attached as additional supported_by on the GO:0006974 DNA damage response annotation. Corroborates existing ICL-repair/DDR decisions; does not change any action. |
No new GO annotations were added. Affinage's remaining five citations (PMID:19801548,
22952942, 23440494, 31511498, 36652992) concern regulation of FANCF, chemoresistance
consequences, or non-human meiotic context, and are appropriately left out of the human
FANCF annotation set.
Net assessment
Affinage's PMID-dense narrative is factually strong and fully aligned with AIGR on FANCF's
core adaptor/FA-core-complex/ICL-repair biology; its value here was surfacing the primary
flexible-adaptor paper (PMID:15262960) and the in-vivo KO paper (PMID:21915857), both now
folded in as supporting evidence for existing decisions. Its weaknesses are the coarse
GO mechanism_profile (which AIGR replaces with granular, correctly-branched terms) and a
tendency to blur regulation-of-FANCF, cancer-phenotype, and cross-species findings into the
gene's own function — over-reaches the conservative AIGR review correctly excludes. Net:
AIGR review is more precise and better scoped; Affinage contributed two well-evidenced
corroborating references but no defensible new function.