BARD1 - dismech genes

Normal function · from ai-gene-review (Q99728, commit 79fe13b38970) · AI-generated, not KB evidence

BARD1 is the BRCA1-associated RING-domain protein that combines nuclear chromatin recognition with regulation of DNA repair. Its N-terminal RING forms a heterodimer with BRCA1, while its ankyrin repeats and tandem BRCT domains recognize nucleosomes bearing unmethylated H4K20 and damage-induced H2A ubiquitin marks. This recognition recruits and positions the BRCA1–BARD1 complex on post-replicative chromatin. BARD1 contributes to the complex's ubiquitin ligase activity toward C-terminal H2A lysines; BRCA1 supplies the demonstrated E2-binding interface. Through separate DNA-binding and RAD51 contacts, the heterodimer promotes homologous DNA pairing and stimulates DNA-end resection machinery during homologous recombination. BARD1 also participates in context-dependent regulation of RNA processing, protein stability and cell survival.

Recognizes ubiquitin-modified nucleosomes and unmodified H4K20 to recruit BRCA1–BARD1 to damaged post-replicative chromatin and position its H2A ubiquitination machinery. The N-terminal H2A ubiquitin marks recognized by BARD1 are distinct from the C-terminal H2A lysines modified by the heterodimer.

molecular function: ubiquitin-modified histone reader activity · contributes to molecular function: histone H2A ubiquitin ligase activity · directly involved in: homologous recombination; protein ubiquitination · locations: nucleus · in complex: BRCA1-BARD1 complex

Contributes RAD51-binding and DNA-binding functions that allow the BRCA1–BARD1 heterodimer to stimulate RAD51-dependent synaptic complex formation and strand invasion during homologous recombination. This activity concerns stimulation of the recombinase rather than the strand-exchange reaction itself or BRCA2-like loading onto RPA-coated single-stranded DNA.

contributes to molecular function: recombinase activator activity · directly involved in: homologous recombination · locations: nucleus · in complex: BRCA1-BARD1 complex

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
BARD1-related Cancer Predisposition	causative germlinesomatic loss of function CLINGEN: definitive	mechanism: Germline BARD1 Loss of Function; Somatic BARD1 Second-Hit Inactivation
Ewing Sarcoma	no genetic record	mechanism: BARD1-Loss and GBP1-Associated DNA-Damage Sensitivity

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
familial ovarian cancer MONDO:0016248	AD	Disputed 2024-08-29	no dismech entry
BARD1-related cancer predisposition MONDO:0700267	AD	Definitive 2024-09-03	BARD1-related Cancer Predisposition causative

Mechanism modules · computed from kb/

germline_two_hit_tumor_predisposition via BARD1-related Cancer Predisposition