PSMB3

protein-coding

proteasome 20S subunit beta 3, the group of Proteasome

Gene summary

The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. The 26 S proteasome may be involved in trinucleotide repeat expansion, a phenomenon which is associated with many hereditary neurological diseases. Pseudogenes have been identified on chromosomes 2 and 12. Alternative splicing results in multiple transcript variants [provided by RefSeq, Sep 2013]

MANE transcript

NM_002795.4

Inheritance

—

ClinVar variants

U:22B:2

Top phenotype

—

Max pathogenic AF

—

Genomic locus

chr17:38,752,741-38,764,225

External References & Databases

Ensembl (ENSG00000277791)

Transcript & Mutation Effects

hg38 • Region Span ~11.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PSMB3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 20

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002795.4. 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				2 clinvar		2
missense			20 clinvar			20
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	22	2	0	24

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002795.4	RefSeq	NP_002786.2	6	MANE Select
ENST00000619426.5	Ensembl	ENSP00000483688.1	6	MANE Select
ENST00000610434.4	Ensembl	ENSP00000478737.1	3	Standard
ENST00000613870.4	Ensembl	ENSP00000481215.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Proteasome - Homo sapiens (human)
Proteasome Degradation
TLR NFkB
proteasome complex
B cell receptor signaling

Biological Process

proteasomal protein catabolic process
proteasomal ubiquitin-independent protein catabolic process
viral process
protein deubiquitination
proteasome-mediated ubiquitin-dependent protein catabolic process

Molecular Function

endopeptidase activity
threonine-type endopeptidase activity
protein binding

Cellular Component

proteasome complex
nucleus
nucleoplasm
cytoplasm
cytosol

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). {ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}.;

Recessive Scores

pRec: 0.309

Intolerance Scores

RVIS EVS: 0.3
RVIS percentile EVS: 72.01

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.990

Gene Damage Prediction

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