Fanconi anemia complementation group B

Summary

Fanconi anemia complementation group B (MONDO:0010351) is a disease caused by FANCB (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: FANCB (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 159

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Fanconi anemia complementation group B
Mondo ID	MONDO:0010351
MeSH	C564497
OMIM	300514
DOID	DOID:0111098
NCIT	C125703
UMLS	C1845292
MedGen	336901
GARD	0015257
Is cancer (heuristic)	no

Also known as: FA2 · FACB · FANCB · Fanconi anaemia complementation group type B · Fanconi anemia complementation group B · Fanconi anemia complementation group type B · Fanconi anemia, complementation group B · Fanconi anemia, complementation group B, X-linked recessive · Fanconi Anemia, complementation group type B

Data availability: 159 ClinVar variants · 4 GenCC gene-disease records · 1 cell line.

Disease family

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

Related subtypes (21): Fanconi anemia complementation group C, Fanconi anemia complementation group D2, Fanconi anemia complementation group A, Fanconi anemia complementation group E, Fanconi anemia complementation group F, Fanconi anemia complementation group D1, 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

159 retrieved; paginated sample, class counts are floors:

76 uncertain significance, 31 conflicting classifications of pathogenicity, 19 pathogenic, 16 benign/likely benign, 10 benign, 4 likely benign, 2 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
10867	FANCB, 3314-BP DEL	FANCB	Pathogenic	no assertion criteria provided
10870	NM_001018113.3(FANCB):c.1496+5G>A	FANCB	Pathogenic	no assertion criteria provided
1395141	NM_001018113.3(FANCB):c.781C>T (p.Arg261Ter)	FANCB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
37043	NM_001018113.3(FANCB):c.2150T>G (p.Leu717Ter)	FANCB	Pathogenic	no assertion criteria provided
37044	NM_001018113.3(FANCB):c.1857_1858del (p.Arg619fs)	FANCB	Pathogenic	criteria provided, single submitter
562389	NM_001018113.3(FANCB):c.1668del (p.Asp557fs)	FANCB	Pathogenic	criteria provided, single submitter
691295	NM_001018113.1(FANCB):c.(?-268)(*160_?)del	FANCB	Pathogenic	no assertion criteria provided
691298	NM_001018113.3(FANCB):c.128T>C (p.Leu43Ser)	FANCB	Pathogenic	no assertion criteria provided
691299	NM_001018113.3(FANCB):c.195dup (p.Thr66fs)	FANCB	Pathogenic	criteria provided, single submitter
691300	NM_001018113.3(FANCB):c.755_767del (p.Leu252fs)	FANCB	Pathogenic	no assertion criteria provided
691301	NM_001018113.3(FANCB):c.829dup (p.Cys277fs)	FANCB	Pathogenic	no assertion criteria provided
691302	NM_001018113.3(FANCB):c.949C>T (p.Gln317Ter)	FANCB	Pathogenic	no assertion criteria provided
691304	NM_001018113.3(FANCB):c.986T>C (p.Leu329Pro)	FANCB	Pathogenic	no assertion criteria provided
691305	NM_001018113.3(FANCB):c.1103C>A (p.Ser368Ter)	FANCB	Pathogenic	no assertion criteria provided
691306	NM_001018113.3(FANCB):c.1497_2580del (p.Ser500fs)	FANCB	Pathogenic	no assertion criteria provided
691307	NM_001018113.3(FANCB):c.1811_1814del (p.Arg604fs)	FANCB	Pathogenic	no assertion criteria provided
691308	NM_001018113.3(FANCB):c.1856_1857insT (p.Arg619fs)	FANCB	Pathogenic	no assertion criteria provided
691311	NM_001018113.3(FANCB):c.2165+1G>T	FANCB	Pathogenic	no assertion criteria provided
691314	NM_001018113.3(FANCB):c.2172_2175del (p.Thr725fs)	FANCB	Pathogenic	no assertion criteria provided
691316	NM_001018113.3(FANCB):c.2249_2252del (p.Gly750fs)	FANCB	Pathogenic	no assertion criteria provided
2582661	NM_001018113.3(FANCB):c.972del (p.Lys324fs)	FANCB	Likely pathogenic	criteria provided, single submitter
3241555	NM_001018113.3(FANCB):c.1570C>T (p.Gln524Ter)	FANCB	Likely pathogenic	criteria provided, single submitter
1005025	NM_001018113.3(FANCB):c.800C>T (p.Ser267Leu)	FANCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1045558	NM_001018113.3(FANCB):c.1838G>C (p.Arg613Pro)	FANCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1047336	NM_001018113.3(FANCB):c.1226G>A (p.Arg409Gln)	FANCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1312584	NM_001018113.3(FANCB):c.1103C>T (p.Ser368Leu)	FANCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1426415	NM_001018113.3(FANCB):c.493G>C (p.Gly165Arg)	FANCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1467792	NM_001018113.3(FANCB):c.1216C>T (p.Arg406Trp)	FANCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1475342	NM_001018113.3(FANCB):c.1327-1G>A	FANCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
197705	NM_001018113.3(FANCB):c.1140T>A (p.Phe380Leu)	FANCB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
FANCB	Definitive	X-linked	Fanconi anemia complementation group B	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FANCB	Orphanet:3412	VACTERL with hydrocephalus
FANCB	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
FANCB	HGNC:3583	ENSG00000181544	Q8NB91	Fanconi anemia group B protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FANCB	Fanconi anemia group B protein	DNA repair protein required for FANCD2 ubiquitination.

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)
FANCB	Other/Unknown	no		FANCB

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
buccal mucosa cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FANCB	160	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, buccal mucosa cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FANCB	1,097

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FANCB	Q8NB91	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Fanconi Anemia Pathway	1	278.5×	0.007	FANCB
PKR-mediated signaling	1	141.0×	0.007	FANCB

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
replication-born double-strand break repair via sister chromatid exchange	1	2808.7×	0.001	FANCB
negative regulation of double-strand break repair via homologous recombination	1	624.1×	0.003	FANCB
interstrand cross-link repair	1	432.1×	0.003	FANCB
positive regulation of double-strand break repair via homologous recombination	1	383.0×	0.003	FANCB

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
FANCB	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	FANCB

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)
FANCB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.