PBRM1 gene is located on chromosome 3p21.1 and spans 140566 base pairs on the minus DNA strand.

20 transcripts have been annotated for the PBRM1 gene (according to Ensembl as of February 2013), which consists of 30 exons.

PBRM1 pseudogenes are not known.

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.

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).

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).

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.

PBRM1 protein is highly conserved across animal kingdom, from flies and worms though all vertebrates to humans.

Germinal mutations of PBRM1 have not been reported.

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).