FANCD2

Chr 3AR

FA complementation group D2

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

NCBI Gene: 2177ENSG00000144554UniProt: Q9BXW9OMIM: 613984

FANCD2 encodes a protein essential for DNA repair through homologous recombination and maintenance of chromosomal stability, particularly during replication stress and meiosis. Mutations cause Fanconi anemia complementation group D2, an autosomal recessive disorder characterized by bone marrow failure, increased cancer risk, and developmental abnormalities. This gene shows minimal constraint against loss-of-function variants in the general population, consistent with its recessive inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.892 OMIM phenotypes
Clinical Summary— FANCD2
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Gene-Disease Validity (ClinGen)
Fanconi anemia complementation group D2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
85 unique Pathogenic / Likely Pathogenic· 243 VUS of 500 total submissions
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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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 OE0.71 (0.58–0.89)
0≤0.351.4
Missense OE1.00 (0.94–1.06)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 60 / 83.9Missense obs/exp: 735 / 737.9Syn Z: 0.53

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic43
VUS243
Likely Benign139
Benign2
Conflicting1
42
Pathogenic
43
Likely Pathogenic
243
VUS
139
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
0
22
0
42
Likely Pathogenic
41
0
2
0
43
VUS
1
212
22
8
243
Likely Benign
0
0
70
69
139
Benign
1
0
1
0
2
Conflicting
—1
Total6321211777470

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in 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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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