MAD2L2 (FANCV / REV7) — AIGR vs Affinage

Warnings (1)

MAD2L2 (FANCV / REV7) — AIGR vs Affinage

Affinage record: run 2026-06-10 · 47 discoveries · self-eval win (faith 100%) · gates passed.

Agreement (brief)

Affinage and the AIGR review converge on the multifunctional core biology, which the
AIGR review already captured well across 3 core_functions and ~79 adjudicated annotations:

The large majority of Affinage's 47 PMIDs were already cited/adjudicated in the AIGR
review (Pol zeta: 20164194, 22828282, 23143872, 11485998; shieldin: 29656893, 29789392,
34354233; APC/C: 11459825, 11459826; mitotic/partner biology: 10366450, 11717438, 17296730,
17541814, 17719540, 19443654, 21063390; TLS/DDR: 15988022, 24449906).

Disagreements

Topic Affinage says AIGR review says Verdict (who is right + why)
MF GO grounding mechanism_profile gives coarse parents: GO:0060090 molecular adaptor, GO:0098772 molecular function regulator, GO:0003677 DNA binding Specific GO:0030674 adaptor activity split across the TLS, shieldin, and APC/C roles AIGR right. Affinage's own note flags the profile as coarse. GO:0003677 DNA binding is not supported — REV7 has no known direct sequence-specific DNA-binding activity; it acts through protein partners. Do not import.
Localization grounding GO:0005634 nucleus + GO:0000228 nuclear chromosome nucleus/nucleoplasm + GO:0035861 site of DSB / GO:0090734 site of DNA damage / GO:0005819 spindle AIGR right/finer. AIGR's damage-site and complex-specific CC terms are more informative than the generic GO:0000228.
Pathway layer Reactome DNA Repair, DNA Replication, Cell Cycle, Disease process terms grounded per-annotation AIGR right. The Reactome buckets are over-general parents; AIGR's per-annotation BP terms carry the actual biology.
APC/C inhibition central mitotic-control finding (PMID:11459825/11459826) ACCEPTED as core (−Ub ligase / APC/C / cell division) Agreement. Both correct; no conflict.
Replication fork protection (PMID:36075897) listed as a 2022 High-confidence finding — shieldin-independent, REV3L/REV1-dependent fork protection limiting MRE11 resection absent Affinage surfaced a real gap. Well-evidenced, MAD2L2-focused Nat Commun study; incorporated as a NEW GO:0110027 annotation (see below).
FANCV / Fanconi anemia (PMID:27500492) stated as disease identity asserted in description but uncited anywhere in the review Affinage right that it needs a citation. The FANCV claim had no supporting reference; incorporated PMID:27500492 onto the DNA-repair annotation.
Germ-cell / PGC maintenance, TRIP13/p31comet disassembly, CHAMP1 competition, p53 signaling (24356953, 23463509, 24009519, 31915374, 33051298, 36044844, 38557443, 38515112) folded into the narrative absent or only implicitly covered AIGR defensibly conservative. Mostly mouse PGC biology, mechanism-of-regulation, or single-group recent human findings; real but peripheral to the human core functions. Noted, not imported.

No factual conflict forces an AIGR reversal. The GO-layer disagreements are the expected
coarse/over-general (and one unsupported DNA binding) grounding; the substantive value was
two MAD2L2-focused papers filling genuine gaps.

Papers incorporated into the review

PMID Supports How used
27500492 REV7/MAD2L2 is Fanconi anemia gene FANCV (biallelic inactivation, REV7-V85E; patient FA phenotype rescued by WT REV7) Added to references (relevance HIGH, VERIFIED) + verbatim supported_by on the existing GO:0006281 DNA repair annotation — supplies the previously-missing citation for the description's FANCV claim
36075897 MAD2L2 protects/restarts stalled replication forks by limiting MRE11-dependent resection, independent of shieldin and requiring REV3L/REV1 Added to references (relevance HIGH, VERIFIED) + one NEW annotation GO:0110027 (negative regulation of DNA strand resection involved in replication fork processing), evidence IMP, with two verbatim supported_by quotes

Both are MAD2L2-focused functional studies. The GO:0110027 term was verified against OLS
(real, non-obsolete, biological_process) and is correctly branched. No existing decision was
weakened. Other Affinage-only PMIDs (25799990, 25799992, 30046110, 30111544, 30154076, 24356953,
23463509, 24009519, 31484720, 31796627, 31915374, 32499490, 33051298, 34521823, 36044844, 38557443,
38515112, 3897794, 7871890, 10366450, 10660610, 12529368, 16227619, 20088965, 23287467, 26697843,
28440919, 28887307, 29160738, 29360267, 29697047, 32811646) were reviewed and not incorporated:
they corroborate already-captured roles, are non-human/ortholog or mouse-developmental, describe
regulation of (not new) MAD2L2 functions, or are single-group recent findings — none altering a
curation call on the human gene.

Net assessment

The AIGR review is the stronger artifact on GO grounding, scoping, and evidence adjudication:
Affinage's mechanism_profile collapses to over-general parents and even asserts an unsupported
DNA binding MF, so its GO layer should not be imported. Affinage's real value is its dense,
dated, PMID-anchored narrative, which surfaced (1) a genuine citation gap for the FANCV/Fanconi
anemia identity and (2) a well-evidenced, shieldin-independent replication fork protection role
(REV3L/REV1-dependent) that the review had missed — the one substantive functional addition beyond
the Pol-zeta / shieldin / APC/C triad. Both were incorporated conservatively without disturbing any
existing decision. 1 new annotation (GO:0110027), 2 papers incorporated, review remains ✓ Valid.