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PBRM1 (polybromo 1)

Written2013-03Rafal Pawlowski
Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland

(Note : for Links provided by Atlas : click)


Alias (NCBI)BAF180
HGNC Alias symbBAF180
LocusID (NCBI) 55193
Atlas_Id 43697
Location 3p21.1  [Link to chromosome band 3p21]
Location_base_pair Starts at 52545367 and ends at 52685913 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping PBRM1.png]
Local_order The PBRM1 gene is located between the NT5DC2 and GLT8D1 genes on chromosome 3p21.1.
  Location of PBRM1 gene on chromosome 3 p21.1. PBRM1 gene is indicated in red, neighbouring genes in blue. Arrows indicate direction.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
DUSP7 (3p21.2)::PBRM1 (3p21.1)GGPS1 (1q42.3)::PBRM1 (3p21.1)NISCH (3p21.1)::PBRM1 (3p21.1)
PBRM1 (3p21.1)::BAP1 (3p21.1)PBRM1 (3p21.1)::CACNA2D3 (3p21.1)PBRM1 (3p21.1)::CYB561D2 (3p21.31)
PBRM1 (3p21.1)::IGSF11 (3q13.32)PBRM1 (3p21.1)::KYNU (2q22.2)PBRM1 (3p21.1)::NEK4 (3p21.1)
PBRM1 (3p21.1)::TKT (3p21.1)PBRM1 (3p21.1)::TMEM110-MUSTN1 (3p21.1)


  The exon-intron organisation of the PBRM1 gene. Exons are shown as dark blue boxes and broken lines connecting the exons indicate introns. Exon and intron sizes are in scale.
Description PBRM1 gene is located on chromosome 3p21.1 and spans 140566 base pairs on the minus DNA strand.
Transcription 20 transcripts have been annotated for the PBRM1 gene (according to Ensembl as of February 2013), which consists of 30 exons.
Pseudogene PBRM1 pseudogenes are not known.


  Schematic diagram of the PBRM1 (BAF180) protein. BD1-6: bromodomain 1-6; BAH1 and BAH2: bromo-adjacent homology domains 1 and 2; HMG: high mobility group domain.
Description Human PBRM1 gene encodes an 1582 amino acid protein, also referred to as BAF180. Six bromodomains (BD1-6), known to recognize acetylated lysine residues and frequently found in chromatin-associated proteins, constitute the N-terminal half of PBRM1. The C-terminal half of PBRM1 contains two bromo-adjacent homology (BAH) domains (BAH1 and BAH2), present in some proteins involved in transcription regulation. High mobility group (HMG) domain is located close to the C-terminus of PBRM1. HMG domains are found in a number of factors regulating DNA-dependent processes where HMG domains often mediate interactions with DNA.
Expression PBRM1 is ubiquitously expressed during mouse embryonic development (Wang et al., 2004), and has been detected in various human tissues including pancreas, kidney, skeletal muscle, liver, lung, placenta, brain, heart, intestine, ovaries, testis, prostate, thymus and spleen (Xue et al., 2000; Horikawa and Barrett, 2002).
Localisation PBRM1 protein localises to the nucleus of cells (Nicolas and Goodwin, 1996). As a component of the PBAF chromatin-remodelling complex, it associates with chromatin (Thompson, 2009), and has been reported to confer the localisation of PBAF complex to the kinetochores of mitotic chromosomes (Xue et al., 2000).
Function PBRM1/BAF180 functions in the regulation of gene expression as a constituent of the evolutionary-conserved SWI/SNF chromatin remodelling complexes (Euskirchen et al., 2012). Beside BRD7 and BAF200, PBRM1 is one of the unique components of the SWI/SNF-B complex also known as polybromo/BRG1-associated factors (or PBAF), absent in the SWI/SNF-A (BAF) complex (Xue et al., 2000; Brownlee et al., 2012). On that account, and because it contains bromodomains known to mediate binding to acetylated histones, PBRM1 has been postulated to target PBAF complex to specific chromatin sites, therefore providing the functional selectivity for the complex (Xue et al., 2000; Lemon et al., 2001; Brownlee et al., 2012). Although direct evidence for PBRM1 involvement is lacking, SWI/SNF complexes have also been shown to play a role in DNA damage response (Park et al., 2006).
In vivo studies have shown that PBRM1 deletion leads to embryonic lethality in mice, where PBRM1 is required for mammalian cardiac chamber maturation and coronary vessel formation (Wang et al., 2004; Huang et al., 2008).
More recently, PBRM1 has acceded the continuously growing group of SWI/SNF subunits frequently mutated in cancer (Wilson and Roberts, 2011; Shain and Pollack, 2013). PBRM1 mutations are most predominant in renal cell carcinomas detected in over 40% of cases, placing PBRM1 second (after VHL) on the list of most frequently mutated genes in this cancer (Varela et al., 2011; Hakimi et al., 2013; Peña-Llopis et al., 2012; Pawlowski et al., 2013). PBRM1 mutations have also been found in a smaller group of breast and pancreatic cancers (Xia et al., 2008; Shain et al., 2012; Numata et al., 2013). Therefore, PBRM1 is considered a novel tumour suppressor in these cancers.
Homology PBRM1 protein is highly conserved across animal kingdom, from flies and worms though all vertebrates to humans.


Germinal Germinal mutations of PBRM1 have not been reported.
Somatic PBRM1 mutations have been found in a large fraction of clear cell renal cell carcinomas (Varela et al., 2011; Duns et al., 2012; Hakimi et al., 2013), and to a smaller extend also in breast (Xia et al., 2008; Shain and Pollack, 2013) and pancreatic cancers (Numata et al., 2013; Shain and Pollack, 2013). The vast majority of PBRM1 mutations found in renal and breast cancers are truncating (nonsense, frameshift insertions and deletions) (Varela et al., 2011; Hakimi et al., 2013).

Implicated in

Entity Renal cell carcinoma (RCC)
Note PBRM1 mutations and/or loss of protein expression have been reported in a large portion of clear cell subtype of RCC (Varela et al., 2011; Duns et al., 2012; Hakimi et al., 2013; Peña-Llopis et al., 2012; Pawlowski et al., 2013). Therefore, PBRM1 has been postulated to function as a tumour suppressor and the second major RCC cancer gene after VHL. PBRM1 mutations are largely mutually exclusive with BAP1 mutations (Peña-Llopis et al., 2012; Kapur et al., 2013).
Prognosis PBRM1 mutations are more common in patients with advance stages (Hakimi et al., 2013) and loss of PBRM1 protein expression has been associated with advanced tumour stage, low differentiation grade and worse patient outcome (Pawlowski et al., 2013). In another study, no correlation between PBRM1 status and tumour grade was found (Peña-Llopis et al., 2012). Although PBRM1-mutant tumours are associated with better prognosis than BAP1-mutant tumours, tumours mutated for both PBRM1 and BAP1 exhibit the greatest aggressiveness (Kapur et al., 2013).
Entity Breast cancer
Note Truncating mutations have been identified in a minority of breast cancers (Xia et al., 2008). In their study, authors showed inhibition of cell proliferation upon PBRM1 re-introduction into a mutant cell line, thus providing direct evidence for tumour suppressing role of PBRM1 in breast cancer.
Entity Pancreatic cancer
Note Mutations in PBRM1 have been reported in a small fraction of pancreatic cancer samples (Numata et al., 2013).


Cancer and the bromodomains of BAF180.
Brownlee PM, Chambers AL, Oliver AW, Downs JA.
Biochem Soc Trans. 2012 Apr;40(2):364-9. doi: 10.1042/BST20110754. (REVIEW)
PMID 22435813
Targeted exome sequencing in clear cell renal cell carcinoma tumors suggests aberrant chromatin regulation as a crucial step in ccRCC development.
Duns G, Hofstra RM, Sietzema JG, Hollema H, van Duivenbode I, Kuik A, Giezen C, Jan O, Bergsma JJ, Bijnen H, van der Vlies P, van den Berg E, Kok K.
Hum Mutat. 2012 Jul;33(7):1059-62. doi: 10.1002/humu.22090. Epub 2012 Apr 30.
PMID 22461374
SWI/SNF chromatin-remodeling factors: multiscale analyses and diverse functions.
Euskirchen G, Auerbach RK, Snyder M.
J Biol Chem. 2012 Sep 7;287(37):30897-905. doi: 10.1074/jbc.R111.309302. Epub 2012 Sep 5. (REVIEW)
PMID 22952240
Clinical and pathologic impact of select chromatin-modulating tumor suppressors in clear cell renal cell carcinoma.
Hakimi AA, Chen YB, Wren J, Gonen M, Abdel-Wahab O, Heguy A, Liu H, Takeda S, Tickoo SK, Reuter VE, Voss MH, Motzer RJ, Coleman JA, Cheng EH, Russo P, Hsieh JJ.
Eur Urol. 2013 May;63(5):848-54. doi: 10.1016/j.eururo.2012.09.005. Epub 2012 Sep 27.
PMID 23036577
cDNA cloning of the human polybromo-1 gene on chromosome 3p21.
Horikawa I, Barrett JC.
DNA Seq. 2002 Aug;13(4):211-5.
PMID 12487023
Coronary development is regulated by ATP-dependent SWI/SNF chromatin remodeling component BAF180.
Huang X, Gao X, Diaz-Trelles R, Ruiz-Lozano P, Wang Z.
Dev Biol. 2008 Jul 15;319(2):258-66. doi: 10.1016/j.ydbio.2008.04.020. Epub 2008 Apr 24.
PMID 18508041
Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation.
Kapur P, Pena-Llopis S, Christie A, Zhrebker L, Pavia-Jimenez A, Rathmell WK, Xie XJ, Brugarolas J.
Lancet Oncol. 2013 Feb;14(2):159-67. doi: 10.1016/S1470-2045(12)70584-3. Epub 2013 Jan 16.
PMID 23333114
Selectivity of chromatin-remodelling cofactors for ligand-activated transcription.
Lemon B, Inouye C, King DS, Tjian R.
Nature. 2001 Dec 20-27;414(6866):924-8.
PMID 11780067
Molecular cloning of polybromo, a nuclear protein containing multiple domains including five bromodomains, a truncated HMG-box, and two repeats of a novel domain.
Nicolas RH, Goodwin GH.
Gene. 1996 Oct 10;175(1-2):233-40.
PMID 8917104
The clinical significance of SWI/SNF complex in pancreatic cancer.
Numata M, Morinaga S, Watanabe T, Tamagawa H, Yamamoto N, Shiozawa M, Nakamura Y, Kameda Y, Okawa S, Rino Y, Akaike M, Masuda M, Miyagi Y.
Int J Oncol. 2013 Feb;42(2):403-10. doi: 10.3892/ijo.2012.1723. Epub 2012 Nov 30.
PMID 23229642
Mammalian SWI/SNF complexes facilitate DNA double-strand break repair by promoting gamma-H2AX induction.
Park JH, Park EJ, Lee HS, Kim SJ, Hur SK, Imbalzano AN, Kwon J.
EMBO J. 2006 Sep 6;25(17):3986-97. Epub 2006 Aug 24.
PMID 16932743
Loss of PBRM1 expression is associated with renal cell carcinoma progression.
Pawlowski R, Muhl SM, Sulser T, Krek W, Moch H, Schraml P.
Int J Cancer. 2013 Jan 15;132(2):E11-7. doi: 10.1002/ijc.27822. Epub 2012 Oct 3.
PMID 22949125
BAP1 loss defines a new class of renal cell carcinoma.
Pena-Llopis S, Vega-Rubin-de-Celis S, Liao A, Leng N, Pavia-Jimenez A, Wang S, Yamasaki T, Zhrebker L, Sivanand S, Spence P, Kinch L, Hambuch T, Jain S, Lotan Y, Margulis V, Sagalowsky AI, Summerour PB, Kabbani W, Wong SW, Grishin N, Laurent M, Xie XJ, Haudenschild CD, Ross MT, Bentley DR, Kapur P, Brugarolas J.
Nat Genet. 2012 Jun 10;44(7):751-9. doi: 10.1038/ng.2323.
PMID 22683710
Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer.
Shain AH, Giacomini CP, Matsukuma K, Karikari CA, Bashyam MD, Hidalgo M, Maitra A, Pollack JR.
Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):E252-9. doi: 10.1073/pnas.1114817109. Epub 2012 Jan 10.
PMID 22233809
The spectrum of SWI/SNF mutations, ubiquitous in human cancers.
Shain AH, Pollack JR.
PLoS One. 2013;8(1):e55119. doi: 10.1371/journal.pone.0055119. Epub 2013 Jan 23.
PMID 23355908
Polybromo-1: the chromatin targeting subunit of the PBAF complex.
Thompson M.
Biochimie. 2009 Mar;91(3):309-19. doi: 10.1016/j.biochi.2008.10.019. Epub 2008 Dec 3. (REVIEW)
PMID 19084573
Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma.
Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P, Davies H, Jones D, Lin ML, Teague J, Bignell G, Butler A, Cho J, Dalgliesh GL, Galappaththige D, Greenman C, Hardy C, Jia M, Latimer C, Lau KW, Marshall J, McLaren S, Menzies A, Mudie L, Stebbings L, Largaespada DA, Wessels LF, Richard S, Kahnoski RJ, Anema J, Tuveson DA, Perez-Mancera PA, Mustonen V, Fischer A, Adams DJ, Rust A, Chan-on W, Subimerb C, Dykema K, Furge K, Campbell PJ, Teh BT, Stratton MR, Futreal PA.
Nature. 2011 Jan 27;469(7331):539-42. doi: 10.1038/nature09639. Epub 2011 Jan 19.
PMID 21248752
Polybromo protein BAF180 functions in mammalian cardiac chamber maturation.
Wang Z, Zhai W, Richardson JA, Olson EN, Meneses JJ, Firpo MT, Kang C, Skarnes WC, Tjian R.
Genes Dev. 2004 Dec 15;18(24):3106-16.
PMID 15601824
SWI/SNF nucleosome remodellers and cancer.
Wilson BG, Roberts CW.
Nat Rev Cancer. 2011 Jun 9;11(7):481-92. doi: 10.1038/nrc3068. (REVIEW)
PMID 21654818
BAF180 is a critical regulator of p21 induction and a tumor suppressor mutated in breast cancer.
Xia W, Nagase S, Montia AG, Kalachikov SM, Keniry M, Su T, Memeo L, Hibshoosh H, Parsons R.
Cancer Res. 2008 Mar 15;68(6):1667-74. doi: 10.1158/0008-5472.CAN-07-5276.
PMID 18339845
The human SWI/SNF-B chromatin-remodeling complex is related to yeast rsc and localizes at kinetochores of mitotic chromosomes.
Xue Y, Canman JC, Lee CS, Nie Z, Yang D, Moreno GT, Young MK, Salmon ED, Wang W.
Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13015-20.
PMID 11078522


This paper should be referenced as such :
Pawlowski, R
PBRM1 (polybromo 1)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(9):605-608.
Free journal version : [ pdf ]   [ DOI ]

External links

HGNC (Hugo)PBRM1   30064
Entrez_Gene (NCBI)PBRM1    polybromo 1
AliasesBAF180; PB1
GeneCards (Weizmann)PBRM1
Ensembl hg19 (Hinxton)ENSG00000163939 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000163939 [Gene_View]  ENSG00000163939 [Sequence]  chr3:52545367-52685913 [Contig_View]  PBRM1 [Vega]
ICGC DataPortalENSG00000163939
TCGA cBioPortalPBRM1
Genatlas (Paris)PBRM1
SOURCE (Princeton)PBRM1
Genetics Home Reference (NIH)PBRM1
Genomic and cartography
GoldenPath hg38 (UCSC)PBRM1  -     chr3:52545367-52685913 -  3p21.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PBRM1  -     3p21.1   [Description]    (hg19-Feb_2009)
GoldenPathPBRM1 - 3p21.1 [CytoView hg19]  PBRM1 - 3p21.1 [CytoView hg38]
Genome Data Viewer NCBIPBRM1 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AA047886 AA724453 AF177387 AF197569 AF225870
RefSeq transcript (Entrez)NM_001350074 NM_001350075 NM_001350076 NM_001350077 NM_001350078 NM_001350079 NM_001366070 NM_001366071 NM_001366072 NM_001366073 NM_001366074 NM_001366075 NM_001366076 NM_001394867 NM_001394868 NM_001394869 NM_001394870 NM_001394871 NM_001394872 NM_001394873 NM_001394874 NM_001394875 NM_001394877 NM_001394878 NM_001394879 NM_001394880 NM_001394881 NM_018165 NM_018313 NM_181041 NM_181042
Consensus coding sequences : CCDS (NCBI)PBRM1
Gene ExpressionPBRM1 [ NCBI-GEO ]   PBRM1 [ EBI - ARRAY_EXPRESS ]   PBRM1 [ SEEK ]   PBRM1 [ MEM ]
Gene Expression Viewer (FireBrowse)PBRM1 [ Firebrowse - Broad ]
GenevisibleExpression of PBRM1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)55193
GTEX Portal (Tissue expression)PBRM1
Human Protein AtlasENSG00000163939-PBRM1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)PBRM1
Human Protein Atlas [tissue]ENSG00000163939-PBRM1 [tissue]
Protein Interaction databases
Complex Portal (EBI) CPX-1196 Polybromo-associated SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6B variant
CPX-1199 Polybromo-associated SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6A variant
Ontologies - Pathways
PubMed147 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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