FANCD2

Chr 3AR

FA complementation group D2

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

NCBI Gene: 2177ENSG00000144554UniProt: Q9BXW9

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]

Primary Disease Associations & Inheritance

Fanconi anemia, complementation group D2MIM #227646
AR
Fanconi anemia, complementation group D2MIM #227646
AR
UniProtFanconi anemia complementation group D2
470
ClinVar variants
55
Pathogenic / LP
0.00
pLI score
4
Active trials
Clinical Summary— FANCD2
🧬
Gene-Disease Validity (ClinGen)
Fanconi anemia complementation group D2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
55 Pathogenic / Likely Pathogenic· 229 VUS of 470 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.89LOEUF
pLI 0.000
Z-score 2.42
OE 0.71 (0.58–0.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.04Z-score
OE missense 1.00 (0.94–1.06)
735 obs / 737.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.71 (0.58–0.89)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.94–1.06)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.96
0≤1.21.6
LoF obs/exp: 60 / 83.9Missense obs/exp: 735 / 737.9Syn Z: 0.53

ClinVar Variant Classifications

470 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic22
VUS229
Likely Benign184
Benign1
Conflicting1
33
Pathogenic
22
Likely Pathogenic
229
VUS
184
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
0
16
0
33
Likely Pathogenic
20
0
2
0
22
VUS
1
201
18
9
229
Likely Benign
0
0
103
81
184
Benign
0
0
1
0
1
Conflicting
—1
Total3820114090470

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.

Gene2Phenotype Curations

FANCD2-related Fanconi anemia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

2 OMIM entries

OMIM
FANCD2 GENE; FANCD2
MIM #613984 · *

Fanconi anemia, complementation group D2

MIM #227646

Molecular basis of disorder known

Autosomal recessive

Fanconi anemia, complementation group D2

MIM #227646

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — FANCD2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
USP1 inhibition: A journey from target discovery to clinical translation.
Torrado C et al.·Pharmacol Ther
2025Review
Phenotypic and genotypic correlation evaluation of 148 pediatric patients with Fanconi anemia in a Chinese rare disease cohort.
Chang L et al.·Clin Chim Acta
2023Cohort
Fanconi anemia.
Soulier J·Hematology Am Soc Hematol Educ Program
2011Review
Genotoxic aldehyde stress prematurely ages hematopoietic stem cells in a p53-driven manner.
Wang M et al.·Mol Cell
2023
The FANCI/FANCD2 complex links DNA damage response to R-loop regulation through SRSF1-mediated mRNA export.
Olazabal-Herrero A et al.·Cell Rep
2024
Germline Variants in DNA Interstrand-Cross Link Repair Genes May Contribute to Increased Susceptibility for Serrated Polyposis Syndrome.
Silva P et al.·Int J Mol Sci
2024
Pathogenic variants reveal candidate genes for prostate cancer germline testing for men of African ancestry.
Gheybi K et al.·Nat Commun
2025
New pathogenic germline variants identified in mesothelioma.
Belcaid L et al.·Lung Cancer
2023Review
Fanconi anemia and ubiquitination.
Zhang Y et al.·J Genet Genomics
2007Review
Prognostic significance of mutation type and chromosome fragility in Fanconi anemia.
Ramírez MJ et al.·Am J Hematol
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
ATM Gene MutationBRCA1 Gene MutationBRCA2 Gene Mutation

Niraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects

ACTIVE NOT RECRUITING
NCT04030559Phase PHASE2Marc Dall'Era, MDStarted 2020-02-25
NiraparibNiraparib Tosylate MonohydrateRadical Prostatectomy
Triple Negative Breast CancerBreast Cancer

Serial Circulating Tumor DNA (ctDNA) Monitoring During Adjuvant Capecitabine in Early Triple-negative Breast Cancer

RECRUITING
NCT04768426Phase PHASE2Stanford UniversityStarted 2021-02-03
Capecitabine
Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING
NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21
NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies
Advanced Solid TumorsEwing SarcomaHepatocellular Carcinoma (HCC)

A Phase 1/1B Study of ST-01156, a Small Molecule RBM39 Degrader, in Patients With Advanced Solid Malignancies

RECRUITING
NCT07197554Phase PHASE1SEED Therapeutics, Inc.Started 2025-12-01
ST-01156

External Resources

Links to major genomics databases and tools