PBRM1

protein-coding

polybromo 1, the group of Bromodomain containing|PBAF complex

Gene summary

This locus encodes a subunit of ATP-dependent chromatin-remodeling complexes. The encoded protein has been identified as in integral component of complexes necessary for ligand-dependent transcriptional activation by nuclear hormone receptors. Mutations at this locus have been associated with primary clear cell renal cell carcinoma. [provided by RefSeq, Feb 2012]

MANE transcript

NM_001405607.1

Inheritance

ClinVar variants

P:1U:58B:13

Top phenotype

Clear cell renal cell carcinoma

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr3:52,545,352-52,685,917

External References & Databases

Ensembl (ENSG00000163939)

Transcript & Mutation Effects

hg38 • Region Span ~140.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Clear cell renal cell carcinomaAD

Manifestation: Oncologic

Intervention: Oncologic

Rationale: Variants have been described as segregating with clear cell renal cell carcinoma, and awareness may be beneficial for surveillance to allow early diagnosis and management

Refs: 25911086

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PBRM1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 26

not providedTotal: 14

Nonpapillary renal cell carcinomaTotal: 3

Hereditary cancerTotal: 2

PBRM1-related BAFopathyTotal: 1

Clear cell carcinoma of kidneyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001405607.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar	11 clinvar	1 clinvar	18
missense			22 clinvar	1 clinvar		23
nonsense			5 clinvar			5
start loss						0
frameshift	1 clinvar		6 clinvar			7
splice donor/acceptor (+/-2bp)			19 clinvar			19
Total	1	0	58	12	1	72

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 222 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001405607.1	RefSeq	NP_001392536.1	31	MANE Select
ENST00000707071.1	Ensembl	ENSP00000516722.1	31	MANE Select
NM_001350074.2	RefSeq	NP_001337003.1	30	Standard
NM_001350075.2	RefSeq	NP_001337004.1	29	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Hepatocellular carcinoma - Homo sapiens (human)
Pathways in clear cell renal cell carcinoma
Gene expression (Transcription)
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known
Generic Transcription Pathway

Biological Process

mitotic cell cycle
nucleosome disassembly
chromatin remodeling
transcription elongation from RNA polymerase II promoter
negative regulation of cell population proliferation

Molecular Function

DNA binding
chromatin binding
protein binding
DNA translocase activity

Cellular Component

nuclear chromosome
nucleoplasm
RSC-type complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000394830
Coding exons: 29
Length: 140566
Individuals with no LoFs: 125673
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125695
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.84	534	849	0.629	0.0000447	10483
Missense (PolyPhen)		54	133.54	0.40437		1539
Synonymous	1.44	259	290	0.893	0.0000148	2863
Loss of Function	7.84	5	81.3	0.0615	0.00000468	1012

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00025	rare
Latino/Admixed American	0.00015	0.000058	rare
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0.00020	0.00011	rare
Finnish	0.00017	0.000092	rare
European (Non-Finnish)	0.000069	0.000053	rare
South Asian	0.00020	0.00013	rare
Other	0.00020	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Required for the stability of the SWI/SNF chromatin remodeling complex SWI/SNF-B (PBAF). Acts as a negative regulator of cell proliferation. {ECO:0000269|PubMed:21248752, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}.;

Recessive Scores

pRec: 0.241

Intolerance Scores

LoFtool: 0.0745
RVIS EVS: -2.15
RVIS percentile EVS: 1.48

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.988

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium