Fanconi anemia complementation group J: genes and variants
Explore variant evidence for Fanconi anemia complementation group J across 12 analyzed proteins (FANCA, FANCD2, RAD51C, ERCC4, RAD51 and 7 more). Linked ClinVar records include 57 pathogenic or likely pathogenic variants, 2,959 variants of uncertain significance and 571 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Fanconi anemia complementation group J
FANCA: Fanconi anemia group A protein
It helps assemble the Fanconi-anemia core complex that monoubiquitinates FANCD2 and FANCI after DNA interstrand crosslinks stall replication. Biallelic loss-of-function variants are the most common cause of Fanconi anemia, with bone-marrow failure and cancer predisposition.
38 ClinVar pathogenic / likely pathogenic and 265 uncertain variants in FANCA have source records linked to Fanconi anemia complementation group J. Association strength is not clinical gene validity.
FANCD2: Fanconi anemia group D2 protein
Its damage-induced monoubiquitination recruits and coordinates nucleases and homologous-recombination factors at stalled replication forks and interstrand crosslinks. Biallelic loss-of-function variants cause Fanconi anemia group D2.
6 ClinVar pathogenic / likely pathogenic and 207 uncertain variants in FANCD2 have source records linked to Fanconi anemia complementation group J. Association strength is not clinical gene validity.
RAD51C: DNA repair protein RAD51 homolog 3
It participates in RAD51-paralog complexes that promote homologous-recombination repair and restart damaged replication forks. Heterozygous loss-of-function variants increase ovarian and breast-cancer risk, while biallelic variants can cause Fanconi anemia.
4 ClinVar pathogenic / likely pathogenic and 710 uncertain variants in RAD51C have source records linked to Fanconi anemia complementation group J. Association strength is not clinical gene validity.
ERCC4: DNA repair endonuclease XPF
Together with ERCC1, it makes structure-specific DNA incisions required for nucleotide-excision repair and interstrand-crosslink repair. Biallelic pathogenic variants can cause xeroderma pigmentosum, Fanconi anemia, or severe progeroid DNA-repair disease.
3 ClinVar pathogenic / likely pathogenic and 352 uncertain variants in ERCC4 have source records linked to Fanconi anemia complementation group J. Association strength is not clinical gene validity.
RAD51: DNA repair protein RAD51 homolog 1
A DNA-repair recombinase that helps find matching DNA sequences and exchange strands during homologous recombination. This pathway repairs DNA breaks and supports genome stability.
3 ClinVar pathogenic / likely pathogenic and 2 uncertain variants in RAD51 have source records linked to Fanconi anemia complementation group J. Association strength is not clinical gene validity.
BRIP1: Fanconi anemia group J protein
It unwinds DNA structures and works with BRCA1 and the Fanconi-anemia pathway to repair damaged replication intermediates and interstrand crosslinks. Biallelic loss causes Fanconi anemia group J, while heterozygous loss-of-function variants increase ovarian-cancer risk.
2 ClinVar pathogenic / likely pathogenic and 1,827 uncertain variants in BRIP1 have source records linked to Fanconi anemia complementation group J. Association strength is not clinical gene validity.
FANCC: Fanconi anemia group C protein
It contributes to activation of the FANCD2-FANCI DNA-repair pathway after replication-blocking lesions. Biallelic loss-of-function variants cause Fanconi anemia group C, with chromosome instability, marrow failure, congenital abnormalities, and elevated cancer risk.
1 ClinVar pathogenic / likely pathogenic and 80 uncertain variants in FANCC have source records linked to Fanconi anemia complementation group J. Association strength is not clinical gene validity.
PALB2: Partner and localizer of BRCA2
It physically links BRCA1 and BRCA2 and helps recruit BRCA2-RAD51 repair machinery to DNA double-strand breaks. Heterozygous loss-of-function variants substantially increase breast and pancreatic cancer risk, while biallelic variants cause Fanconi anemia subtype N.
0 ClinVar pathogenic / likely pathogenic and 62 uncertain variants in PALB2 have source records linked to Fanconi anemia complementation group J. Association strength is not clinical gene validity.
XRCC2: DNA repair protein XRCC2
It acts with other RAD51 paralogs to assemble and stabilize homologous-recombination repair machinery at DNA double-strand breaks. Biallelic loss-of-function variants can cause Fanconi-anemia-like chromosome-instability disease, while heterozygous cancer-risk associations are less certain.
0 ClinVar pathogenic / likely pathogenic and 21 uncertain variants in XRCC2 have source records linked to Fanconi anemia complementation group J. Association strength is not clinical gene validity.
BRCA1: Breast cancer type 1 susceptibility protein
It coordinates DNA-damage signaling and homologous-recombination repair while helping protect stalled replication forks and chromosome integrity. Germline loss-of-function variants strongly predispose to breast and ovarian cancer and increase risk for several other malignancies.
0 ClinVar pathogenic / likely pathogenic and 2 uncertain variants in BRCA1 have source records linked to Fanconi anemia complementation group J. Association strength is not clinical gene validity.
BRCA2: Breast cancer type 2 susceptibility protein
It loads RAD51 onto damaged DNA to enable homologous recombination and also protects stressed replication forks from degradation. Germline loss-of-function variants strongly predispose to breast, ovarian, prostate, pancreatic, and other cancers.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in BRCA2 have source records linked to Fanconi anemia complementation group J. Association strength is not clinical gene validity.
POLG: DNA polymerase subunit gamma-1
It replicates and repairs mitochondrial DNA and is therefore essential for maintaining mitochondrial genome copy number and integrity. Pathogenic variants cause a broad spectrum including Alpers syndrome, progressive external ophthalmoplegia, epilepsy, ataxia, neuropathy, and liver disease.
0 ClinVar pathogenic / likely pathogenic and 2 uncertain variants in POLG have source records linked to Fanconi anemia complementation group J. Association strength is not clinical gene validity.
ClinVar pathogenic and likely pathogenic variants linked to Fanconi anemia complementation group J
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| FANCA Q436R | 436 | Pathogenic / likely pathogenic (★★) | |
| FANCA P1164S | 1164 | Pathogenic / likely pathogenic (★★) | |
| RAD51C C135F | 135 | Interaction with RAD51B, RAD51D and XRCC3 | Pathogenic / likely pathogenic (★★) |
| RAD51C C135S | 135 | Interaction with RAD51B, RAD51D and XRCC3 | Pathogenic / likely pathogenic (★★) |
| ERCC4 C236R | 236 | Leucine-zipper 1 | Pathogenic / likely pathogenic (★★) |
| ERCC4 R689S | 689 | ERCC4 | Pathogenic / likely pathogenic (★★) |
| FANCA R764W | 764 | Pathogenic / likely pathogenic (★★) | |
| FANCA R1055Q | 1055 | Pathogenic / likely pathogenic (★★) | |
| RAD51 E258K | 258 | Nuclear export signal | Pathogenic / likely pathogenic (★★) |
| RAD51C G125V | 125 | Interaction with RAD51B, RAD51D and XRCC3 | Pathogenic / likely pathogenic (★★) |
| BRIP1 Q169H | 169 | Helicase ATP-binding | Pathogenic / likely pathogenic (★★) |
| FANCA E878Q | 878 | Pathogenic / likely pathogenic (★★) | |
| FANCA H1110P | 1110 | Pathogenic / likely pathogenic (★★) | |
| FANCD2 S126G | 126 | Interaction with FANCE | Pathogenic / likely pathogenic (★★) |
| FANCD2 R302W | 302 | Interaction with BRCA2 | Pathogenic / likely pathogenic (★★) |
| FANCD2 R815Q | 815 | Pathogenic / likely pathogenic (★★) | |
| FANCD2 R1236H | 1236 | Pathogenic / likely pathogenic (★★) | |
| RAD51C E191K | 191 | Pathogenic / likely pathogenic (★★) | |
| FANCA L324P | 324 | Pathogenic / likely pathogenic (★) | |
| FANCA R951L | 951 | Pathogenic / likely pathogenic (★) | |
| FANCA F456S | 456 | Pathogenic / likely pathogenic (★) | |
| RAD51 T197I | 197 | Interaction with PALB2 | Pathogenic / likely pathogenic (★) |
| FANCA V389L | 389 | Pathogenic / likely pathogenic (★) | |
| FANCA E420K | 420 | Pathogenic / likely pathogenic (★) | |
| FANCD2 L457P | 457 | Pathogenic / likely pathogenic (★) | |
| FANCA L358R | 358 | Pathogenic / likely pathogenic | |
| FANCA Y448C | 448 | Pathogenic / likely pathogenic | |
| FANCA T724P | 724 | Pathogenic / likely pathogenic | |
| FANCA Y843D | 843 | Pathogenic / likely pathogenic | |
| FANCA W932R | 932 | Pathogenic / likely pathogenic | |
| FANCA E936K | 936 | Pathogenic / likely pathogenic | |
| ERCC4 L230P | 230 | Helicase-like | Pathogenic / likely pathogenic |
| FANCA L210R | 210 | Pathogenic / likely pathogenic | |
| FANCA L362P | 362 | Pathogenic / likely pathogenic | |
| FANCA L407R | 407 | Pathogenic / likely pathogenic | |
| FANCA Q742K | 742 | Pathogenic / likely pathogenic | |
| FANCA V761E | 761 | Pathogenic / likely pathogenic | |
| FANCA R1204P | 1204 | Pathogenic / likely pathogenic | |
| FANCA F1262L | 1262 | Pathogenic / likely pathogenic | |
| FANCA A1357P | 1357 | Pathogenic / likely pathogenic | |
| FANCA M1360I | 1360 | Pathogenic / likely pathogenic | |
| FANCA A1399P | 1399 | Pathogenic / likely pathogenic | |
| RAD51 T131P | 131 | Pathogenic / likely pathogenic | |
| BRIP1 Q255H | 255 | Helicase ATP-binding | Pathogenic / likely pathogenic |
| FANCA D598N | 598 | Pathogenic / likely pathogenic | |
| FANCA A788P | 788 | Pathogenic / likely pathogenic | |
| FANCA L817P | 817 | Pathogenic / likely pathogenic | |
| FANCA T838R | 838 | Pathogenic / likely pathogenic | |
| FANCA L908P | 908 | Pathogenic / likely pathogenic | |
| FANCA D1129V | 1129 | Pathogenic / likely pathogenic | |
| FANCC L496R | 496 | Pathogenic / likely pathogenic | |
| FANCD2 L231R | 231 | Interaction with FANCE | Pathogenic / likely pathogenic |
| FANCA R685T | 685 | Pathogenic / likely pathogenic | |
| FANCA R1080L | 1080 | Pathogenic / likely pathogenic | |
| FANCA D1325H | 1325 | Pathogenic / likely pathogenic | |
| FANCA S1337G | 1337 | Pathogenic / likely pathogenic | |
| FANCA A228G | 228 | Pathogenic / likely pathogenic |
Uncertain variants prioritized for review in Fanconi anemia complementation group J
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| RAD51C C135R | 135 | Interaction with RAD51B, RAD51D and XRCC3 | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; C135F at the same position is pathogenic; seen in 2.7e-06 of gnomAD DNA copies; REVEL 0.759 |
| RAD51C C135W | 135 | Interaction with RAD51B, RAD51D and XRCC3 | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; C135F at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.92 |
Which prediction tools work for Fanconi anemia complementation group J
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- MetaLR: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 92 out of 100
- EVE: 91 out of 100
- PolyPhen-2: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- REVEL: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 87 out of 100
- AlphaMissense: 86 out of 100
- phyloP: 84 out of 100
- MutPred2: 80 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Same protein, different disease
- Fanconi anemia also has ClinVar records linked to FANCA variants; they fall partly in the same places as the Fanconi anemia complementation group J variants (15 pathogenic / likely pathogenic).
- Breast-ovarian cancer, familial, susceptibility to, 1 also has ClinVar records linked to RAD51C variants; they fall mostly in different places as the Fanconi anemia complementation group J variants (9 pathogenic / likely pathogenic).
Diseases related to Fanconi anemia complementation group J
- Fanconi anemia, also linked to BRCA2, BRIP1, ERCC4, FANCA and 7 more
- Ovarian cancer, also linked to BRCA1, BRCA2, BRIP1, ERCC4 and 4 more
- Hereditary breast ovarian cancer syndrome, also linked to BRCA1, BRCA2, BRIP1, FANCC and 3 more
- Acute myeloid leukemia, also linked to ERCC4, FANCA, FANCC, FANCD2 and 1 more
- Breast-ovarian cancer, familial, susceptibility to, 1, also linked to BRCA1, BRCA2, BRIP1, PALB2 and 1 more
- Hereditary breast cancer, also linked to BRCA1, BRCA2, BRIP1 and PALB2
- Gastric cancer, also linked to BRIP1, PALB2 and RAD51C
- Ovarian neoplasm, also linked to BRCA1, BRCA2 and BRIP1
- Familial pancreatic carcinoma, also linked to BRCA1, BRCA2 and PALB2
- Breast and/or ovarian cancer, also linked to BRIP1 and RAD51C
- Familial ovarian cancer, also linked to BRIP1 and RAD51C
- Progressive sclerosing poliodystrophy, also linked to POLG
Frequently asked questions
Which genes have records linked to Fanconi anemia complementation group J?
This view contains 12 analyzed proteins: FANCA, FANCD2, RAD51C, ERCC4, RAD51 and 7 more. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 57 pathogenic or likely pathogenic variants, 2,959 variants of uncertain significance and 571 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 2 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 3,802 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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