FANCC (FANCC) — AIGR vs Affinage
Affinage record: run 2026-06-09 · 34 discoveries · self-eval win (faith 100%) · gates passed.
Affinage supplies a strong, PMID-dense mechanistic narrative (34 citation-anchored findings)
plus a coarse mechanism_profile GO/Reactome layer. The AIGR review is the curated,
GOA-grounded, validated review (41 GOA annotations reviewed; status: COMPLETE).
Agreement (brief)
- Core role is identical. Both place FANCC as a non-catalytic subunit of the nuclear FA
core complex (with FANCA/E/F/G) required for FANCD2–FANCI monoubiquitination and
replication-coupled interstrand cross-link (ICL) repair; both flag the L554P patient
mutation as abolishing FANCA/FANCE binding and complementing activity. - Substrate-recognition module. Affinage's "FANCC–FANCE–FANCF anti-crossover subcomplex"
and complex-assembly interdependencies match the AIGRcore_functionsadaptor model
(molecular adaptor activity contributing to the complex's ubiquitin-ligase activity). - Dual localization. Both record a major nuclear form and a minor cytoplasmic pool
(GRP94/HSP70 associated). - Non-core signaling/redox roles are real but separable. Both acknowledge the cytoplasmic
anti-apoptotic (PKR/Hsp70), IFN-γ/STAT1, and redox/detoxification roles; AIGR files them as
non-core, and Affinage's own cited evidence supports that separability (see below).
Disagreements
| Topic | Affinage says | AIGR review says | Verdict (who is right + why) |
|---|---|---|---|
| MF grounding | mechanism_profile: molecular adaptor activity, molecular function regulator activity, DNA binding (GO:0003677) |
Molecular adaptor activity (informative MF replacing protein binding); no DNA-binding MF |
AIGR. Affinage's DNA-binding call rests on FANCA/C/G co-purifying on psoralen-crosslinked DNA affinity columns (PMID:11401546) — a complex-level pulldown, not evidence FANCC is a sequence/structure-specific DNA-binding protein. Importing GO:0003677 would over-annotate. |
| Coarse pathway layer | Reactome tags include Programmed Cell Death, Signal Transduction, Autophagy, Reproduction as co-equal to DNA Repair | Core = ICL repair / complex assembly; apoptosis, STAT1 signaling, autophagy, meiotic anti-crossover treated as non-core / out of GOA scope | AIGR. The flat Reactome layer loses the core-vs-non-core distinction. The deep-research note itself warns this grounding "collapses to general parents and can contradict the narrative." |
| STAT1/PKR anti-apoptotic role | Emphasized as a major independent function of cytoplasmic FANCC | Kept as non-core, structurally separable from ICL repair | AIGR (and Affinage's own citations confirm it). PMID:12397061 and PMID:11520787 show FANCC mutants that lose PKR/STAT1 function still complement MMC sensitivity and FANCD2 activation — separable, hence non-core. Affinage's evidence does not change the call. |
| NER | Not asserted | GO:0006289 nucleotide-excision repair MARK_AS_OVER_ANNOTATED |
No conflict; AIGR is more precise (ICL repair, not classical NER). |
Over-reaches AIGR correctly excludes
- DNA binding (GO:0003677) — Affinage
mechanism_profileonly; unsupported at the FANCC
monomer level (see table). - Large-scale/network
protein bindinginteractions (SMAD4, FBXW7, MEOX2, AKT1) — AIGR marks
these over-annotated; Affinage does not surface them (correctly ignores).
Functions AIGR previously under-cited (now strengthened from Affinage papers)
- Redox/detoxification basis of the oxidative-stress annotation — Affinage surfaced
PMID:9787138 (FANCC attenuates NADPH cytochrome P450 reductase), which is the actual redox
evidence the AIGR reason invoked; it previously cited only a STAT1 study. - Interdependent FA complex assembly — PMID:11063725 (FANCF nuclear complex; loss of any
FA protein except FANCD disrupts assembly) strengthens the complex-assembly annotation.
Papers incorporated into the review
| PMID | Supports | How used |
|---|---|---|
| PMID:11063725 | Interdependent FA core complex assembly | Added supported_by on GO:0065003 (protein-containing complex assembly) + reference_review (MEDIUM/VERIFIED) |
| PMID:9787138 | FANCC redox/detoxification (NADPH cytochrome P450 reductase) | Added supported_by on GO:0034599 (cellular response to oxidative stress, non-core) + reference_review (MEDIUM/VERIFIED) |
| PMID:12397061 | FANCC–Hsp70–PKR anti-apoptotic function, independent of the FA complex | Added as reference with reference_review (MEDIUM/VERIFIED); documents non-core PKR role and confirms its structural separability |
No NEW GO annotations were added: the anti-apoptotic/STAT1/redox functions have no matching
GOA annotation and remain correctly scoped as non-core context in the description, so adding
new core-level terms was not warranted.
Net assessment
The AIGR review and Affinage agree on all core biology; the review is more disciplined on GO
grounding (informative adaptor MF instead of coarse regulator/DNA-binding tags; explicit
core-vs-non-core partitioning that Affinage's flat Reactome layer erases). Affinage's chief
value here was surfacing well-cited older primary papers (redox/RED, FANCF interdependence,
PKR separability) that let us attach verbatim support to two existing annotations and
substantiate the non-core signaling roles. Affinage's evidence reinforces rather than
overturns the review's non-core calls for the STAT1/PKR/redox functions. No factual conflicts
requiring a change of any existing annotation decision. Validation: ✓ Valid.