BARD1 (BRCA1 associated RING domain 1)

2007-02-01   Irmgard Irminger-Finger 

Biology of Aging Laboratory, Dept of Geriatrics, Dept of Gynecology, Obstetrics, Geneva University, University Hospitals, 30, Bloulevard de la Cluse, CH-1211 Geneva, Switzerland




Atlas Image
BARD1 structure is presented with RING finger (green) ankyrin repeats (ANK, blue) and BRCT domains (red). Positions of introns (in) are indicated. Structures of splice variants are shown for BARD1beta from the rat (Feki et al., 2004), BARD1delta (Feki et al., 2005; Tsuzuki et al., 2006).


The gene spans 81 kb, composed of 11 exons. Alternatively spliced isoforms are identified.
Insert known isoforms:
BARD1beta (rat testis)
BARD1delta (rat ovarian cancer cells)
BARD1delta (HeLa)
BARD1delta (rat ovarian cancer cells)


Transcription start is 100 bp upstream of first ATG of the BARD1 ORF. There a two 3ends reported and possibly two alternative polyadenylation sites. BARD1 is expressed in most proliferative tissues. Highest expression in testis and spleen. No expression the central nervous system.


No pseudogenes reported.


Atlas Image
Mouse and human BARD1 protein sequences are shown schematically. RING finger domains (gren), Ankyrin repeats (ANK, blue), BRCT domains (red), nulear localization signals (light blue). Homology between human and mouse BARD1 is indicated in perentage of identical amino acids for structural regions.


Human BARD1 777 amino acids ; Structural motifs: RING, 5 Ankyrin repeats, 2 BRCT domains


In the mouse BARD1 is expressed in most proliferative tissues. Highest expression in testis and spleen, no expression in nervous system.
During mouse development BARD1 is expressed in early embryogenesis and declines after day 9.


During S-phase BARD1 localizes to nuclear dots. Partially, BARD1 is also localized to the cytoplasm in response to stress.


BARD1 functions as heterodimer with BRCA1 as ubiquitin ligase. Several targets of the BARD1-BRCA1 ubiquitin ligase have been identified and suggest its implication in DNA repair, polyadenylation, cell cycle control, and mitosis.
BARD1 acts as inducer of apoptosis, independently of BRCA1, by binding to p53, and by binding to the stress response kinase DNA-PK, facilitating p53 phosphorylation and stabilization. Thus BARD1 acts as signaling molecule from genotoxic stress towards p53-dependent apoptosis.


BARD1 is homologous to BRCA1, regarding the N-terminal RING finger and the C-terminal BRCT domains. Weak homology between BARD1 and BRCA1 can be found throughout exon 1 to exon 4. and from exon 7 through exon 11, with conserved intron-exon junctions.



Several mutations of BARD1 have been identified in breast and ovarian cancers. Three mutations have been reported associated with inherited predisposition to breast and ovarian cancer.
Atlas Image
BARD1 mutations associated with cancer. Small mutations are not unambiguously identified as cancer causing mutations, long arrows red labeled mutations are accepted as cancer associated. Blue indication maps germ line mutations. Q406R, might be cancer associated.


Germline mutations were reported for C557S and Q564H.


Several somatic mutation were reported in addition to C557S and Q564H:

Implicated in

Entity name
Breast and/or ovarian cancer
Upregulated expression of truncated BARD1 in epithelial cancers.
Upregulated BARD1 is correlated with poor prognosis in breast and ovarian cancer.
No determined
Hybrid gene
Not determined
Fusion protein
No fusion proteins reported
Entity name
Ovarian cancer
Upregulated BARD1 is correlated with poor prognosis in breast and ovarian cancer.
Hybrid gene
Fusion protein
No fusion proteins reported
Entity name
Lung cancer
Upregulated BARD1 is correlated with poor prognosis in breast and ovarian cancer.
Hybrid gene
Fusion protein
No fusion proteins reported


Pubmed IDLast YearTitleAuthors
97986861998Conservation of function and primary structure in the BRCA1-associated RING domain (BARD1) protein.Ayi TC et al
115730852001Structure of a BRCA1-BARD1 heterodimeric RING-RING complex.Brzovic PS et al
119275912002Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase.Chen A et al
97749701998Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells.Chen J et al
121540232002The BRCA1 and BARD1 association with the RNA polymerase II holoenzyme.Chiba N et al
158551572005Hyperphosphorylation of the BARD1 tumor suppressor in mitotic cells.Choudhury AD et al
103623521999The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and nuclear co-regulators.Dechend R et al
119254362002BARD1 induces BRCA1 intranuclear foci formation by increasing RING-dependent BRCA1 nuclear import and inhibiting BRCA1 nuclear export.Fabbro M et al
151593972004BRCA1-BARD1 complexes are required for p53Ser-15 phosphorylation and a G1/S arrest following ionizing radiation-induced DNA damage.Fabbro M et al
152657112004BARD1 regulates BRCA1 apoptotic function by a mechanism involving nuclear retention.Fabbro M et al
157821302005BARD1 induces apoptosis by catalysing phosphorylation of p53 by DNA-damage response kinase.Feki A et al
111563882000Identification of an apoptotic cleavage product of BARD1 as an autoantigen: a potential factor in the antitumoral response mediated by apoptotic bodies.Gautier F et al
118079802002Germline mutations of the BRCA1-associated ring domain (BARD1) gene in breast and breast/ovarian families negative for BRCA1 and BRCA2 alterations.Ghimenti C et al
160070732005Role of nucleophosmin in embryonic development and tumorigenesis.Grisendi S et al
112782472001The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation.Hashizume R et al
156652732005Down-regulation of BRCA1-BARD1 ubiquitin ligase by CDK2.Hayami R et al
166333662006Is there more to BARD1 than BRCA1?Irminger-Finger I et al
145509462003Mutational analysis of BARD1 in familial breast cancer patients in Japan.Ishitobi M et al
150771852004Nuclear-cytoplasmic translocation of BARD1 is linked to its apoptotic activity.Jefford CE et al
170819762006The BRCA1/BARD1 heterodimer modulates ran-dependent mitotic spindle assembly.Joukov V et al
168254372006Nordic collaborative study of the BARD1 Cys557Ser allele in 3956 patients with cancer: enrichment in familial BRCA1/BRCA2 mutation-negative breast cancer but not in other malignancies.Karppinen SM et al
159054102005BRCA1/BARD1 inhibition of mRNA 3' processing involves targeted degradation of RNA polymerase II.Kleiman FE et al
171853942007Ubiquitination and proteasome-mediated degradation of BRCA1 and BARD1 during steroidogenesis in human ovarian granulosa cells.Lu Y et al
124859962002Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains.Mallery DL et al
128324892003Loss of Bard1, the heterodimeric partner of the Brca1 tumor suppressor, results in early embryonic lethality and chromosomal instability.McCarthy EE et al
117730712002Identification of residues required for the interaction of BARD1 with BRCA1.Morris JR et al
149761652004BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair.Morris JR et al
117990672002E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints.Ren B et al
146474302004Nuclear-cytoplasmic shuttling of BARD1 contributes to its proapoptotic activity and is regulated by dimerization with BRCA1.Rodriguez JA et al
151843792004Nucleophosmin/B23 is a candidate substrate for the BRCA1-BARD1 ubiquitin ligase.Sato K et al
156321372005Nuclear targeting and cell cycle regulatory function of human BARD1.Schüchner S et al
91591191997BRCA1 is a component of the RNA polymerase II holoenzyme.Scully R et al
92670231997Dynamic changes of BRCA1 subnuclear location and phosphorylation state are initiated by DNA damage.Scully R et al
121834112002Interaction of the EWS NH2 terminus with BARD1 links the Ewing's sarcoma gene to a common tumor suppressor pathway.Spahn L et al
167685472006The BARD1 Cys557Ser variant and breast cancer risk in Iceland.Stacey SN et al
158862012005BRCA1/BARD1 ubiquitinate phosphorylated RNA polymerase II.Starita LM et al
154859002004Genetic steps of mammalian homologous repair with distinct mutagenic consequences.Stark JM et al
94252261998Mutations in the BRCA1-associated RING domain (BARD1) gene in primary breast, ovarian and uterine cancers.Thai TH et al
158782322006A truncated splice variant of human BARD1 that lacks the RING finger and ankyrin repeats.Tsuzuki M et al
163333122006BARD1 variants Cys557Ser and Val507Met in breast cancer predisposition.Vahteristo P et al
145600352003BARD1 participates with BRCA1 in homology-directed repair of chromosome breaks.Westermark UK et al
161526122006Aberrant expression of BARD1 in breast and ovarian cancers with poor prognosis.Wu JY et al
89440231996Identification of a RING protein that can interact in vivo with the BRCA1 gene product.Wu LC et al

Other Information

Locus ID:

NCBI: 580
MIM: 601593
HGNC: 952
Ensembl: ENSG00000138376


dbSNP: 580
ClinVar: 580
TCGA: ENSG00000138376


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Homologous recombinationKEGGko03440
Homologous recombinationKEGGhsa03440
Metabolism of proteinsREACTOMER-HSA-392499
Post-translational protein modificationREACTOMER-HSA-597592
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
Cell CycleREACTOMER-HSA-1640170
Cell Cycle CheckpointsREACTOMER-HSA-69620
G2/M CheckpointsREACTOMER-HSA-69481
G2/M DNA damage checkpointREACTOMER-HSA-69473
DNA Double-Strand Break RepairREACTOMER-HSA-5693532
DNA Double Strand Break ResponseREACTOMER-HSA-5693606
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaksREACTOMER-HSA-5693565
Homology Directed RepairREACTOMER-HSA-5693538
HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)REACTOMER-HSA-5693567
Processing of DNA double-strand break endsREACTOMER-HSA-5693607
HDR through Homologous Recombination (HRR)REACTOMER-HSA-5685942
Homologous DNA Pairing and Strand ExchangeREACTOMER-HSA-5693579
Presynaptic phase of homologous DNA pairing and strand exchangeREACTOMER-HSA-5693616
Resolution of D-Loop StructuresREACTOMER-HSA-5693537
Resolution of D-loop Structures through Holliday Junction IntermediatesREACTOMER-HSA-5693568
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)REACTOMER-HSA-5693554
HDR through Single Strand Annealing (SSA)REACTOMER-HSA-5685938
Nonhomologous End-Joining (NHEJ)REACTOMER-HSA-5693571
Regulation of TP53 ActivityREACTOMER-HSA-5633007
Regulation of TP53 Activity through PhosphorylationREACTOMER-HSA-6804756
UCH proteinasesREACTOMER-HSA-5689603
Metalloprotease DUBsREACTOMER-HSA-5689901

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA443560Breast NeoplasmsDiseaseClinicalAnnotationassociatedPD30071039


Pubmed IDYearTitleCitations
194121752009Common variations in BARD1 influence susceptibility to high-risk neuroblastoma.137
194121752009Common variations in BARD1 influence susceptibility to high-risk neuroblastoma.137
284184442017Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer.109
124859962002Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains.90
128906882003The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin.87
149761652004BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair.84
146386902004Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase.73
124319962003Enhancement of BRCA1 E3 ubiquitin ligase activity through direct interaction with the BARD1 protein.72
272397952016Human BRCA1-BARD1 ubiquitin ligase activity counteracts chromatin barriers to DNA resection.69
119275912002Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase.62


Irmgard Irminger-Finger

BARD1 (BRCA1 associated RING domain 1)

Atlas Genet Cytogenet Oncol Haematol. 2007-02-01

Online version: