Atlas of Genetics and Cytogenetics in Oncology and Haematology

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BARD1 (BRCA1 associated RING domain 1)

Written2007-02Irmgard 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

(Note : for Links provided by Atlas : click)


Other aliasBRCA1-associated RING domain protein 1
LocusID (NCBI) 580
Atlas_Id 756
Location 2q35  [Link to chromosome band 2q35]
Location_base_pair Starts at and ends at bp from pter
Local_order Antiparallel
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
BARD1 (2q35) / CASC4 (15q15.3)


  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).
Description 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 Transcription start is 100 bp upstream of first ATG of the BARD1 ORF. There a two 3'ends 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.
Pseudogene No pseudogenes reported.


  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.
Description Human BARD1 777 amino acids ; Structural motifs: RING, 5 Ankyrin repeats, 2 BRCT domains
Expression 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.
Localisation During S-phase BARD1 localizes to nuclear dots. Partially, BARD1 is also localized to the cytoplasm in response to stress.
Function 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.
Homology 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.


Note 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.
  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.
Germinal Germline mutations were reported for C557S and Q564H.
Somatic Several somatic mutation were reported in addition to C557S and Q564H:

Implicated in

Entity Breast and/or ovarian cancer
Note Upregulated expression of truncated BARD1 in epithelial cancers.
Prognosis Upregulated BARD1 is correlated with poor prognosis in breast and ovarian cancer.
Cytogenetics No determined
Hybrid/Mutated Gene Not determined
Abnormal Protein No fusion proteins reported
Entity Ovarian cancer
Prognosis Upregulated BARD1 is correlated with poor prognosis in breast and ovarian cancer.
Hybrid/Mutated Gene No
Abnormal Protein No fusion proteins reported
Entity Lung cancer
Prognosis Upregulated BARD1 is correlated with poor prognosis in breast and ovarian cancer.
Hybrid/Mutated Gene No
Abnormal Protein No fusion proteins reported


Conservation of function and primary structure in the BRCA1-associated RING domain (BARD1) protein.
Ayi TC, Tsan JT, Hwang LY, Bowcock AM, Baer R
Oncogene. 1998 ; 17 (16) : 2143-2148.
PMID 9798686
Structure of a BRCA1-BARD1 heterodimeric RING-RING complex.
Brzovic PS, Rajagopal P, Hoyt DW, King MC, Klevit RE
Nature structural biology. 2001 ; 8 (10) : 833-837.
PMID 11573085
Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase.
Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ
The Journal of biological chemistry. 2002 ; 277 (24) : 22085-22092.
PMID 11927591
Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells.
Chen J, Silver DP, Walpita D, Cantor SB, Gazdar AF, Tomlinson G, Couch FJ, Weber BL, Ashley T, Livingston DM, Scully R
Molecular cell. 1998 ; 2 (3) : 317-328.
PMID 9774970
The BRCA1 and BARD1 association with the RNA polymerase II holoenzyme.
Chiba N, Parvin JD
Cancer research. 2002 ; 62 (15) : 4222-4228.
PMID 12154023
Hyperphosphorylation of the BARD1 tumor suppressor in mitotic cells.
Choudhury AD, Xu H, Modi AP, Zhang W, Ludwig T, Baer R
The Journal of biological chemistry. 2005 ; 280 (26) : 24669-24679.
PMID 15855157
The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and nuclear co-regulators.
Dechend R, Hirano F, Lehmann K, Heissmeyer V, Ansieau S, Wulczyn FG, Scheidereit C, Leutz A
Oncogene. 1999 ; 18 (22) : 3316-3323.
PMID 10362352
BARD1 induces BRCA1 intranuclear foci formation by increasing RING-dependent BRCA1 nuclear import and inhibiting BRCA1 nuclear export.
Fabbro M, Rodriguez JA, Baer R, Henderson BR
The Journal of biological chemistry. 2002 ; 277 (24) : 21315-21324.
PMID 11925436
BRCA1-BARD1 complexes are required for p53Ser-15 phosphorylation and a G1/S arrest following ionizing radiation-induced DNA damage.
Fabbro M, Savage K, Hobson K, Deans AJ, Powell SN, McArthur GA, Khanna KK
The Journal of biological chemistry. 2004 ; 279 (30) : 31251-31258.
PMID 15159397
BARD1 regulates BRCA1 apoptotic function by a mechanism involving nuclear retention.
Fabbro M, Schuechner S, Au WW, Henderson BR
Experimental cell research. 2004 ; 298 (2) : 661-673.
PMID 15265711
BARD1 induces apoptosis by catalysing phosphorylation of p53 by DNA-damage response kinase.
Feki A, Jefford CE, Berardi P, Wu JY, Cartier L, Krause KH, Irminger-Finger I
Oncogene. 2005 ; 24 (23) : 3726-3736.
PMID 15782130
Identification of an apoptotic cleavage product of BARD1 as an autoantigen: a potential factor in the antitumoral response mediated by apoptotic bodies.
Gautier F, Irminger-Finger I, Grégoire M, Meflah K, Harb J
Cancer research. 2000 ; 60 (24) : 6895-6900.
PMID 11156388
Germline mutations of the BRCA1-associated ring domain (BARD1) gene in breast and breast/ovarian families negative for BRCA1 and BRCA2 alterations.
Ghimenti C, Sensi E, Presciuttini S, Brunetti IM, Conte P, Bevilacqua G, Caligo MA
Genes, chromosomes & cancer. 2002 ; 33 (3) : 235-242.
PMID 11807980
Role of nucleophosmin in embryonic development and tumorigenesis.
Grisendi S, Bernardi R, Rossi M, Cheng K, Khandker L, Manova K, Pandolfi PP
Nature. 2005 ; 437 (7055) : 147-153.
PMID 16007073
The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation.
Hashizume R, Fukuda M, Maeda I, Nishikawa H, Oyake D, Yabuki Y, Ogata H, Ohta T
The Journal of biological chemistry. 2001 ; 276 (18) : 14537-14540.
PMID 11278247
Down-regulation of BRCA1-BARD1 ubiquitin ligase by CDK2.
Hayami R, Sato K, Wu W, Nishikawa T, Hiroi J, Ohtani-Kaneko R, Fukuda M, Ohta T
Cancer research. 2005 ; 65 (1) : 6-10.
PMID 15665273
Is there more to BARD1 than BRCA1?
Irminger-Finger I, Jefford CE
Nature reviews. Cancer. 2006 ; 6 (5) : 382-391.
PMID 16633366
Mutational analysis of BARD1 in familial breast cancer patients in Japan.
Ishitobi M, Miyoshi Y, Hasegawa S, Egawa C, Tamaki Y, Monden M, Noguchi S
Cancer letters. 2003 ; 200 (1) : 1-7.
PMID 14550946
Nuclear-cytoplasmic translocation of BARD1 is linked to its apoptotic activity.
Jefford CE, Feki A, Harb J, Krause KH, Irminger-Finger I
Oncogene. 2004 ; 23 (20) : 3509-3520.
PMID 15077185
The BRCA1/BARD1 heterodimer modulates ran-dependent mitotic spindle assembly.
Joukov V, Groen AC, Prokhorova T, Gerson R, White E, Rodriguez A, Walter JC, Livingston DM
Cell. 2006 ; 127 (3) : 539-552.
PMID 17081976
Nordic 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, Barkardottir RB, Backenhorn K, Sydenham T, Syrjäkoski K, Schleutker J, Ikonen T, Pylkäs K, Rapakko K, Erkko H, Johannesdottir G, Gerdes AM, Thomassen M, Agnarsson BA, Grip M, Kallioniemi A, Kere J, Aaltonen LA, Arason A, M&oring;ller P, Kruse TA, Borg A, Winqvist R
Journal of medical genetics. 2006 ; 43 (11) : 856-862.
PMID 16825437
BRCA1/BARD1 inhibition of mRNA 3' processing involves targeted degradation of RNA polymerase II.
Kleiman FE, Wu-Baer F, Fonseca D, Kaneko S, Baer R, Manley JL
Genes & development. 2005 ; 19 (10) : 1227-1237.
PMID 15905410
Ubiquitination and proteasome-mediated degradation of BRCA1 and BARD1 during steroidogenesis in human ovarian granulosa cells.
Lu Y, Amleh A, Sun J, Jin X, McCullough SD, Baer R, Ren D, Li R, Hu Y
Molecular endocrinology (Baltimore, Md.). 2007 ; 21 (3) : 651-663.
PMID 17185394
Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains.
Mallery DL, Vandenberg CJ, Hiom K
The EMBO journal. 2002 ; 21 (24) : 6755-6762.
PMID 12485996
Loss of Bard1, the heterodimeric partner of the Brca1 tumor suppressor, results in early embryonic lethality and chromosomal instability.
McCarthy EE, Celebi JT, Baer R, Ludwig T
Molecular and cellular biology. 2003 ; 23 (14) : 5056-5063.
PMID 12832489
Identification of residues required for the interaction of BARD1 with BRCA1.
Morris JR, Keep NH, Solomon E
The Journal of biological chemistry. 2002 ; 277 (11) : 9382-9386.
PMID 11773071
BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair.
Morris JR, Solomon E
Human molecular genetics. 2004 ; 13 (8) : 807-817.
PMID 14976165
E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints.
Ren B, Cam H, Takahashi Y, Volkert T, Terragni J, Young RA, Dynlacht BD
Genes & development. 2002 ; 16 (2) : 245-256.
PMID 11799067
Nuclear-cytoplasmic shuttling of BARD1 contributes to its proapoptotic activity and is regulated by dimerization with BRCA1.
Rodriguez JA, Schüchner S, Au WW, Fabbro M, Henderson BR
Oncogene. 2004 ; 23 (10) : 1809-1820.
PMID 14647430
Nucleophosmin/B23 is a candidate substrate for the BRCA1-BARD1 ubiquitin ligase.
Sato K, Hayami R, Wu W, Nishikawa T, Nishikawa H, Okuda Y, Ogata H, Fukuda M, Ohta T
The Journal of biological chemistry. 2004 ; 279 (30) : 30919-30922.
PMID 15184379
Nuclear targeting and cell cycle regulatory function of human BARD1.
Schüchner S, Tembe V, Rodriguez JA, Henderson BR
The Journal of biological chemistry. 2005 ; 280 (10) : 8855-8861.
PMID 15632137
BRCA1 is a component of the RNA polymerase II holoenzyme.
Scully R, Anderson SF, Chao DM, Wei W, Ye L, Young RA, Livingston DM, Parvin JD
Proceedings of the National Academy of Sciences of the United States of America. 1997 ; 94 (11) : 5605-5610.
PMID 9159119
Dynamic changes of BRCA1 subnuclear location and phosphorylation state are initiated by DNA damage.
Scully R, Chen J, Ochs RL, Keegan K, Hoekstra M, Feunteun J, Livingston DM
Cell. 1997 ; 90 (3) : 425-435.
PMID 9267023
Interaction of the EWS NH2 terminus with BARD1 links the Ewing's sarcoma gene to a common tumor suppressor pathway.
Spahn L, Petermann R, Siligan C, Schmid JA, Aryee DN, Kovar H
Cancer research. 2002 ; 62 (16) : 4583-4587.
PMID 12183411
The BARD1 Cys557Ser variant and breast cancer risk in Iceland.
Stacey SN, Sulem P, Johannsson OT, Helgason A, Gudmundsson J, Kostic JP, Kristjansson K, Jonsdottir T, Sigurdsson H, Hrafnkelsson J, Johannsson J, Sveinsson T, Myrdal G, Grimsson HN, Bergthorsson JT, Amundadottir LT, Gulcher JR, Thorsteinsdottir U, Kong A, Stefansson K
PLoS medicine. 2006 ; 3 (7) : page e217.
PMID 16768547
BRCA1/BARD1 ubiquitinate phosphorylated RNA polymerase II.
Starita LM, Horwitz AA, Keogh MC, Ishioka C, Parvin JD, Chiba N
The Journal of biological chemistry. 2005 ; 280 (26) : 24498-24505.
PMID 15886201
Genetic steps of mammalian homologous repair with distinct mutagenic consequences.
Stark JM, Pierce AJ, Oh J, Pastink A, Jasin M
Molecular and cellular biology. 2004 ; 24 (21) : 9305-9316.
PMID 15485900
Mutations in the BRCA1-associated RING domain (BARD1) gene in primary breast, ovarian and uterine cancers.
Thai TH, Du F, Tsan JT, Jin Y, Phung A, Spillman MA, Massa HF, Muller CY, Ashfaq R, Mathis JM, Miller DS, Trask BJ, Baer R, Bowcock AM
Human molecular genetics. 1998 ; 7 (2) : 195-202.
PMID 9425226
A truncated splice variant of human BARD1 that lacks the RING finger and ankyrin repeats.
Tsuzuki M, Wu W, Nishikawa H, Hayami R, Oyake D, Yabuki Y, Fukuda M, Ohta T
Cancer letters. 2006 ; 233 (1) : 108-116.
PMID 15878232
BARD1 variants Cys557Ser and Val507Met in breast cancer predisposition.
Vahteristo P, Syrjäkoski K, Heikkinen T, Eerola H, Aittomäki K, von Smitten K, Holli K, Blomqvist C, Kallioniemi OP, Nevanlinna H
European journal of human genetics : EJHG. 2006 ; 14 (2) : 167-172.
PMID 16333312
BARD1 participates with BRCA1 in homology-directed repair of chromosome breaks.
Westermark UK, Reyngold M, Olshen AB, Baer R, Jasin M, Moynahan ME
Molecular and cellular biology. 2003 ; 23 (21) : 7926-7936.
PMID 14560035
Aberrant expression of BARD1 in breast and ovarian cancers with poor prognosis.
Wu JY, Vlastos AT, Pelte MF, Caligo MA, Bianco A, Krause KH, Laurent GJ, Irminger-Finger I
International journal of cancer. Journal international du cancer. 2006 ; 118 (5) : 1215-1226.
PMID 16152612
Identification of a RING protein that can interact in vivo with the BRCA1 gene product.
Wu LC, Wang ZW, Tsan JT, Spillman MA, Phung A, Xu XL, Yang MC, Hwang LY, Bowcock AM, Baer R
Nature genetics. 1996 ; 14 (4) : 430-440.
PMID 8944023


This paper should be referenced as such :
Irminger-Finger, I
BARD1 (BRCA1 associated RING domain 1)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(3):173-176.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 3 ]
  t(2;7)(q35;q21) GTPBP10/BARD1
t(8;17)(q24;q22) ???BCL3/MYC
t(2;7)(q35;q21) GTPBP10/BARD1

External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)580
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
canSAR (ICR) (select the gene name)
REVIEW articlesautomatic search in PubMed
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