Fanconi anemia complementation group D1

Summary

Fanconi anemia complementation group D1 (MONDO:0011584) is a disease caused by BRCA2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: BRCA2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 598

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Fanconi anemia complementation group D1
Mondo ID	MONDO:0011584
MeSH	C563980
OMIM	605724
Orphanet	319462
DOID	DOID:0111089
NCIT	C125705
SNOMED CT	766707003
UMLS	C1838457
MedGen	325420
GARD	0017449
Is cancer (heuristic)	no

Also known as: FAD1 · FANCD1 · Fanconi anemia complementation group D1 · Fanconi anemia, complementation group D1

Data availability: 598 ClinVar variants · 4 GenCC gene-disease records · 9 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › congenital anemia › Fanconi anemia › Fanconi anemia complementation group D1

Related subtypes (21): Fanconi anemia complementation group C, Fanconi anemia complementation group D2, Fanconi anemia complementation group A, Fanconi anemia complementation group B, Fanconi anemia complementation group E, Fanconi anemia complementation group F, Fanconi anemia complementation group I, Fanconi anemia complementation group J, Fanconi anemia complementation group N, Fanconi anemia complementation group O, Fanconi anemia complementation group P, Fanconi anemia complementation group G, Fanconi anemia complementation group L, Fanconi anemia complementation group Q, Fanconi anemia complementation group T, Fanconi anemia complementation group V, Fanconi anemia complementation group R, Fanconi anemia complementation group U, Fanconi anemia, complementation group W, Fanconi anemia, complementation group S, fanconi anemia, complementation group 10

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

598 retrieved; paginated sample, class counts are floors:

215 conflicting classifications of pathogenicity, 172 pathogenic, 103 benign, 43 uncertain significance, 30 likely benign, 18 pathogenic/likely pathogenic, 9 likely pathogenic, 8 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
126014	NM_000059.4(BRCA2):c.3458del (p.Lys1153fs)	BRCA2	Pathogenic	reviewed by expert panel
126037	NM_000059.4(BRCA2):c.4131_4132insTGAGGA (p.Thr1378Ter)	BRCA2	Pathogenic	reviewed by expert panel
126199	NM_000059.4(BRCA2):c.9082G>C (p.Ala3028Pro)	BRCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126217	NM_000059.4(BRCA2):c.9672dup (p.Tyr3225fs)	BRCA2	Pathogenic	reviewed by expert panel
1330148	NM_000059.4(BRCA2):c.6611del (p.Pro2204fs)	BRCA2	Pathogenic	criteria provided, multiple submitters, no conflicts
1332800	NM_000059.4(BRCA2):c.4733T>G (p.Leu1578Ter)	BRCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141199	NM_000059.4(BRCA2):c.2918C>A (p.Ser973Ter)	BRCA2	Pathogenic	reviewed by expert panel
141283	NM_000059.4(BRCA2):c.1909+1G>A	BRCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141509	NM_000059.4(BRCA2):c.6816_6820del (p.Gly2274fs)	BRCA2	Pathogenic	reviewed by expert panel
142868	NM_000059.4(BRCA2):c.2059_2063del (p.Leu686_Asp687insTer)	BRCA2	Pathogenic	reviewed by expert panel
1439264	NM_000059.4(BRCA2):c.1766dup (p.Phe590fs)	BRCA2	Pathogenic	criteria provided, multiple submitters, no conflicts
1456139	NM_000059.4(BRCA2):c.4793_4794del (p.Leu1598fs)	BRCA2	Pathogenic	criteria provided, multiple submitters, no conflicts
1706564	NM_000059.4(BRCA2):c.658dup (p.Val220fs)	BRCA2	Pathogenic	criteria provided, single submitter
1737126	NM_000059.4(BRCA2):c.4022C>G (p.Ser1341Ter)	BRCA2	Pathogenic	criteria provided, multiple submitters, no conflicts
182322	NM_000059.4(BRCA2):c.8174_8185delinsTT (p.Trp2725fs)	BRCA2	Pathogenic	reviewed by expert panel
182326	NM_000059.4(BRCA2):c.9891_9894dup (p.Gln3299fs)	BRCA2	Pathogenic	reviewed by expert panel
187127	NM_000059.4(BRCA2):c.4914dup (p.Val1639fs)	BRCA2	Pathogenic	reviewed by expert panel
2076041	NM_000059.4(BRCA2):c.6341del (p.Pro2114fs)	BRCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
216855	NM_000059.4(BRCA2):c.4515_4525del (p.Phe1506fs)	BRCA2	Pathogenic	reviewed by expert panel
252446	NM_000059.4(BRCA2):c.6466_6469del (p.Ser2156fs)	BRCA2	Pathogenic	reviewed by expert panel
254498	NM_000059.4(BRCA2):c.2279del (p.Leu760fs)	BRCA2	Pathogenic	reviewed by expert panel
254509	NM_000059.4(BRCA2):c.2905C>T (p.Gln969Ter)	BRCA2	Pathogenic	reviewed by expert panel
254585	NM_000059.4(BRCA2):c.6623del (p.Asn2208fs)	BRCA2	Pathogenic	reviewed by expert panel
254605	NM_000059.4(BRCA2):c.7464_7465insTA (p.Asp2489Ter)	BRCA2	Pathogenic	reviewed by expert panel
254630	NM_000059.4(BRCA2):c.9246dup (p.Lys3083fs)	BRCA2	Pathogenic	reviewed by expert panel
266762	NM_000059.4(BRCA2):c.3631G>T (p.Glu1211Ter)	BRCA2	Pathogenic	reviewed by expert panel
267053	NM_000059.4(BRCA2):c.805dup (p.Thr269fs)	BRCA2	Pathogenic	reviewed by expert panel
267696	NM_000059.4(BRCA2):c.8332-1G>A	BRCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
267711	NM_000059.4(BRCA2):c.8954-15T>G	BRCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3062039	NM_000059.4(BRCA2):c.4125_4138del (p.Glu1375fs)	BRCA2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 12 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
BRCA2	Definitive	Autosomal recessive	Fanconi anemia complementation group D1	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRCA2	Orphanet:1331	Familial prostate cancer
BRCA2	Orphanet:1333	Familial pancreatic carcinoma
BRCA2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA2	Orphanet:178	Chordoma
BRCA2	Orphanet:227535	Hereditary breast cancer
BRCA2	Orphanet:319462	Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations
BRCA2	Orphanet:440437	Familial colorectal cancer Type X
BRCA2	Orphanet:654	Nephroblastoma
BRCA2	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA2	Orphanet:694963	Inflammatory breast cancer
BRCA2	Orphanet:70567	Cholangiocarcinoma
BRCA2	Orphanet:84	Fanconi anemia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
secondary oocyte	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRCA2	4,839

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRCA2	P51587	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 27. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Impaired BRCA2 translocation to the nucleus	1	3806.7×	0.004	BRCA2
Impaired BRCA2 binding to SEM1 (DSS1)	1	3806.7×	0.004	BRCA2
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	951.7×	0.005	BRCA2
HDR through MMEJ (alt-NHEJ)	1	878.5×	0.005	BRCA2
Diseases of DNA Double-Strand Break Repair	1	815.7×	0.005	BRCA2
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	815.7×	0.005	BRCA2
Resolution of D-Loop Structures	1	634.4×	0.005	BRCA2
Diseases of DNA repair	1	571.0×	0.005	BRCA2
Impaired BRCA2 binding to PALB2	1	456.8×	0.005	BRCA2
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	423.0×	0.005	BRCA2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	423.0×	0.005	BRCA2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	423.0×	0.005	BRCA2
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	393.8×	0.005	BRCA2
Homologous DNA Pairing and Strand Exchange	1	380.7×	0.005	BRCA2
Homology Directed Repair	1	308.6×	0.005	BRCA2
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1	308.6×	0.005	BRCA2
Impaired BRCA2 binding to RAD51	1	308.6×	0.005	BRCA2
Resolution of D-loop Structures through Holliday Junction Intermediates	1	300.5×	0.005	BRCA2
Meiosis	1	285.5×	0.005	BRCA2
Presynaptic phase of homologous DNA pairing and strand exchange	1	271.9×	0.005	BRCA2
DNA Double-Strand Break Repair	1	248.3×	0.005	BRCA2
Reproduction	1	190.3×	0.006	BRCA2
HDR through Homologous Recombination (HRR)	1	190.3×	0.006	BRCA2
Meiotic recombination	1	129.8×	0.009	BRCA2
DNA Repair	1	98.5×	0.011	BRCA2
Cell Cycle	1	36.0×	0.029	BRCA2
Disease	1	13.1×	0.076	BRCA2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mitotic recombination-dependent replication fork processing	1	8426.0×	0.003	BRCA2
negative regulation of mammary gland epithelial cell proliferation	1	3370.4×	0.003	BRCA2
establishment of protein localization to telomere	1	2106.5×	0.003	BRCA2
response to UV-C	1	1685.2×	0.003	BRCA2
telomere maintenance via recombination	1	1532.0×	0.003	BRCA2
regulation of DNA damage checkpoint	1	1123.5×	0.003	BRCA2
inner cell mass cell proliferation	1	991.3×	0.003	BRCA2
centrosome duplication	1	936.2×	0.003	BRCA2
response to X-ray	1	887.0×	0.003	BRCA2
female gonad development	1	802.5×	0.003	BRCA2
hematopoietic stem cell proliferation	1	648.1×	0.003	BRCA2
oocyte maturation	1	601.9×	0.003	BRCA2
male meiosis I	1	581.1×	0.003	BRCA2
response to gamma radiation	1	581.1×	0.003	BRCA2
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1	495.6×	0.004	BRCA2
positive regulation of mitotic cell cycle	1	468.1×	0.004	BRCA2
regulation of cytokinesis	1	421.3×	0.004	BRCA2
cellular response to ionizing radiation	1	411.0×	0.004	BRCA2
nucleotide-excision repair	1	383.0×	0.004	BRCA2
DNA damage response, signal transduction by p53 class mediator	1	358.6×	0.004	BRCA2
cellular senescence	1	295.6×	0.004	BRCA2
double-strand break repair	1	203.0×	0.006	BRCA2
double-strand break repair via homologous recombination	1	156.0×	0.008	BRCA2
brain development	1	79.5×	0.014	BRCA2
spermatogenesis	1	35.2×	0.031	BRCA2
regulation of DNA-templated transcription	1	31.6×	0.033	BRCA2
positive regulation of DNA-templated transcription	1	27.9×	0.036	BRCA2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BRCA2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	BRCA2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
BRCA2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.