Fanconi anemia complementation group J

Summary

Fanconi anemia complementation group J (MONDO:0012187) is a disease caused by BRIP1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: BRIP1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 4,540

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Fanconi anemia complementation group J
Mondo ID	MONDO:0012187
MeSH	C563801
OMIM	609054
DOID	DOID:0111097
NCIT	C129027
UMLS	C1836860
MedGen	323015
GARD	0015449
Is cancer (heuristic)	no

Also known as: FANCJ · Fanconi anaemia complementation group type J · Fanconi anemia complementation group J · Fanconi anemia complementation group type J · Fanconi anemia, complementation group J · Fanconi Anemia, complementation group type J

Data availability: 4,540 ClinVar variants · 4 GenCC gene-disease records · 4 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 J

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 D1, Fanconi anemia complementation group I, 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

600 retrieved; paginated sample, class counts are floors:

304 uncertain significance, 80 conflicting classifications of pathogenicity, 62 likely benign, 61 benign/likely benign, 52 pathogenic, 26 pathogenic/likely pathogenic, 12 likely pathogenic, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1066430	NM_032043.3(BRIP1):c.508-2A>C	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068503	NM_032043.3(BRIP1):c.1488_1500del (p.Val497fs)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1068821	NM_032043.3(BRIP1):c.1289_1290dup (p.Arg431Ter)	BRIP1	Pathogenic	criteria provided, single submitter
1069129	NM_032043.3(BRIP1):c.2670del (p.Val891fs)	BRIP1	Pathogenic	criteria provided, single submitter
1069454	NM_032043.3(BRIP1):c.71dup (p.Gln25fs)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1069522	NM_032043.3(BRIP1):c.251T>A (p.Leu84Ter)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1069754	NM_032043.3(BRIP1):c.1699A>T (p.Lys567Ter)	BRIP1	Pathogenic	criteria provided, single submitter
1070348	NM_032043.3(BRIP1):c.2197del (p.Thr733fs)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1070392	NC_000017.10:g.(?59861621)(59861795_?)del	BRIP1	Pathogenic	criteria provided, single submitter
1070540	NM_032043.3(BRIP1):c.1256_1278dup (p.Asn427delinsGlyMetAsnTer)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1072409	NM_032043.3(BRIP1):c.2519_2520insCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGAGATCGAGACCANNNNNNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGAAATGATTGGGG (p.Gly840_Ala841insArgAlaArgTrpLeuThrProValIleProAlaLeuTrpGluAlaGluAlaGlyGlySerArgGlyGlnGluIleGluThrXaaXaaXaaXaaXaaXaaLysLysLysLysLysLysLysLysLysLysArgAsnAspTrpGly)	BRIP1	Pathogenic	criteria provided, single submitter
1073531	NM_032043.3(BRIP1):c.2111T>G (p.Leu704Ter)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1073805	NM_032043.3(BRIP1):c.1709T>A (p.Leu570Ter)	BRIP1	Pathogenic	criteria provided, single submitter
1073980	NM_032043.3(BRIP1):c.505_506insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGAGGTCAGGAGATCGAGACCATCCTGGCTAACAAGGTGAAACCCCGTCTCTACTAAAAATACAAAAAATTAGCCGGGCGCGGTGGCGGGCGCCTGTAGTCCCAGCTACTCGGGAGGCTGAGGCAGGAGAATGGCGTGAACCCGGGAAGCGGAGCTTGCAGTGAGCCGAGATTGCGCCACTGCAGTCCACAGTCCGGCCTGGGCGACAGAGCGAGACTCCGTCTCAAAAAAATAAAATAAAATAAAATAAAATAAAATAAAAAAAAAAAAAAAAAAAAAAAAAAACTACACAGC (p.Gln169delinsArgProGlyAlaValAlaHisAlaCysAsnProSerThrLeuGlyGlyArgGlyGlyTrpIleMetArgSerGlyAspArgAspHisProGlyTer)	BRIP1	Pathogenic	criteria provided, single submitter
1074046	NM_032043.3(BRIP1):c.254C>G (p.Ser85Ter)	BRIP1	Pathogenic	criteria provided, single submitter
1074235	NM_032043.3(BRIP1):c.1801del (p.Ser601fs)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1074435	NC_000017.10:g.(?59770781)(59938900_?)del	BRIP1	Pathogenic	criteria provided, single submitter
1074436	NC_000017.10:g.(?59926480)(59934602_?)del	BRIP1	Pathogenic	criteria provided, single submitter
1074437	NC_000017.10:g.(?59876451)(59886128_?)del	BRIP1	Pathogenic	criteria provided, single submitter
1074541	NM_032043.3(BRIP1):c.386dup (p.Pro129_Glu130insTer)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1075199	NM_032043.3(BRIP1):c.2109del (p.Lys703fs)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1075294	NM_032043.3(BRIP1):c.1457del (p.Thr486fs)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1075663	NM_032043.3(BRIP1):c.2833G>T (p.Glu945Ter)	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075963	NM_032043.3(BRIP1):c.984_990del (p.Phe328fs)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1076101	NM_032043.3(BRIP1):c.2716G>T (p.Glu906Ter)	BRIP1	Pathogenic	criteria provided, single submitter
1076124	NM_032043.3(BRIP1):c.1959_1960dup (p.Gly654fs)	BRIP1	Pathogenic	criteria provided, single submitter
1076359	NC_000017.10:g.(?59760657)(59821962_?)del	BRIP1	Pathogenic	criteria provided, single submitter
1076496	NM_032043.3(BRIP1):c.1058dup (p.Tyr353Ter)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1076574	NM_032043.3(BRIP1):c.1378_1379del (p.Asp460fs)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1076680	NM_032043.3(BRIP1):c.1356_1371del (p.Asn452fs)	BRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 2 · 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
BRIP1	Definitive	Autosomal recessive	Fanconi anemia	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRIP1	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRIP1	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
BRIP1	HGNC:20473	ENSG00000136492	Q9BX63	Fanconi anemia group J protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRIP1	Fanconi anemia group J protein	DNA-dependent ATPase and 5’-3’ DNA helicase required for the maintenance of chromosomal stability.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRIP1	Enzyme (other)	yes	3.6.4.12	Helicase-like_DEXD_c2, ATP-dep_Helicase_C, RAD3-like_helicase_DEAD

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
primordial germ cell in gonad	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRIP1	181	ubiquitous	marker	ventricular zone, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRIP1	2,272

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRIP1	Q9BX63	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. 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
Cytosolic iron-sulfur cluster assembly	1	761.3×	0.005	BRIP1
Impaired BRCA2 binding to PALB2	1	456.8×	0.005	BRIP1
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	423.0×	0.005	BRIP1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	423.0×	0.005	BRIP1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	423.0×	0.005	BRIP1
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	393.8×	0.005	BRIP1
Homologous DNA Pairing and Strand Exchange	1	380.7×	0.005	BRIP1
Impaired BRCA2 binding to RAD51	1	308.6×	0.005	BRIP1
Resolution of D-loop Structures through Holliday Junction Intermediates	1	300.5×	0.005	BRIP1
HDR through Single Strand Annealing (SSA)	1	292.8×	0.005	BRIP1
Presynaptic phase of homologous DNA pairing and strand exchange	1	271.9×	0.005	BRIP1
HDR through Homologous Recombination (HRR)	1	190.3×	0.007	BRIP1
G2/M DNA damage checkpoint	1	120.2×	0.009	BRIP1
Regulation of TP53 Activity through Phosphorylation	1	117.7×	0.009	BRIP1
Processing of DNA double-strand break ends	1	114.2×	0.009	BRIP1

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
meiotic DNA double-strand break processing involved in reciprocal meiotic recombination	1	5617.3×	0.002	BRIP1
spermatogonial cell division	1	3370.4×	0.002	BRIP1
chiasma assembly	1	1872.4×	0.002	BRIP1
protein-DNA covalent cross-linking repair	1	1685.2×	0.002	BRIP1
homologous recombination	1	1404.3×	0.002	BRIP1
double-strand break repair involved in meiotic recombination	1	1296.3×	0.002	BRIP1
seminiferous tubule development	1	766.0×	0.002	BRIP1
DNA damage checkpoint signaling	1	391.9×	0.004	BRIP1
nucleotide-excision repair	1	383.0×	0.004	BRIP1
double-strand break repair	1	203.0×	0.006	BRIP1
spermatid development	1	145.3×	0.008	BRIP1
DNA repair	1	63.8×	0.017	BRIP1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	BRIP1

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
BRIP1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRIP1	3.6.4.12	DNA helicase

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	1	BRIP1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
BRIP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.