FANCD2

Chr 3AR

FA complementation group D2

Also known as: FA-D2, FA4, FACD, FAD, FAD2, FANCD

NCBI Gene: 2177ENSG00000144554UniProt: Q9BXW9OMIM: 613984

The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group D2. This protein is monoubiquinated in response to DNA damage, resulting in its localization to nuclear foci with other proteins (BRCA1 AND BRCA2) involved in homology-directed DNA repair. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Fanconi anemia, complementation group D2MIM #227646
AR
Fanconi anemia, complementation group D2MIM #227646
AR
UniProtFanconi anemia complementation group D2

Clinical highlights

Gene-disease validity (ClinGen)
Fanconi anemia complementation group D2 · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
3
Active trials
101
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.89
LOEUF
LOF
Mechanism· G2P
📖
GeneReview available — FANCD2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.89LOEUF
pLI 0.000
Z-score 2.42
OE 0.71 (0.58–0.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.04Z-score
OE missense 1.00 (0.94–1.06)
735 obs / 737.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.71 (0.58–0.89)
0≤0.351.4
Missense OE?1.00 (0.94–1.06)
0≤0.61.4
Synonymous OE?0.96
0≤1.21.6
LoF obs/exp: 60 / 83.9Missense obs/exp: 735 / 737.9Syn Z: 0.53

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

FANCD2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients