GeneBe

PSMB4

protein-coding

proteasome 20S subunit beta 4, 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. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002796.3

Inheritance

AR, Digenic

ClinVar variants

P:1U:153B:54

Top phenotype

Proteasome-associated autoinflammatory syndrome 3

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr1:151,399,560-151,401,937

External References & Databases

Ensembl (ENSG00000159377)NCBI Gene (5692)OMIM (602177)HGNC:9541GenCCUniProt (P28070)AlphaFoldClinVar (PSMB4)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~2.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

proteasome-associated autoinflammatory syndrome 3LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0054699

Submitter: Labcorp Genetics (formerly Invitae)

proteasome-associated autoinflammatory syndrome 3LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0054699

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Proteasome-associated autoinflammatory syndrome 3AR/Digenic

Manifestation: Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic

Intervention: Allergy/Immunology/Infectious

Rationale: Individuals may have recurrent infections, and awareness may allow preventative measures as well as prompt and agressive treatment of infections

Comments: Digenic inheritance has been reported

Refs: 26524591Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PSMB4 variants in ClinVar

6 Conditions Cataloged
not providedTotal: 260
not specifiedTotal: 51
PSMB4-related disorderTotal: 6
Proteasome-associated autoinflammatory syndrome 3Total: 4
Muscular dystrophyTotal: 1
Proteasome-associated autoinflammatory syndrome 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002796.3. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
46
clinvar
1
clinvar
 49
missense
138
clinvar
6
clinvar
 144
nonsense
1
clinvar
3
clinvar
 4
start loss
2
clinvar
1
clinvar
 3
frameshift
5
clinvar
 5
splice donor/acceptor (+/-2bp)
3
clinvar
 3
Total10153531208
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002796.3RefSeqNP_002787.27MANE Select
ENST00000290541.7EnsemblENSP00000290541.67MANE Select
ENST00000933662.1EnsemblENSP00000603721.16Standard
ENST00000933663.1EnsemblENSP00000603722.16Standard

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

  • negative regulation of inflammatory response to antigenic stimulus
  • proteasomal protein catabolic process
  • proteasomal ubiquitin-independent protein catabolic process
  • viral process
  • protein deubiquitination

Molecular Function

  • lipopolysaccharide binding
  • endopeptidase activity
  • threonine-type endopeptidase activity
  • protein binding

Cellular Component

  • proteasome complex
  • nucleus
  • nucleoplasm
  • cytoplasm
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000290541
Coding exons
7
Length
2411
Individuals with no LoFs
125732
Homozygous LoFs
0
Heterozygous LoFs
16
Defined
125748
p
0.0000636
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.4671421590.8960.000009171697
Missense (PolyPhen)2552.4790.47638546
Synonymous0.1235960.20.9800.00000349546
Loss of Function2.18716.60.4229.69e-7167

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.000120.00012rare
Ashkenazi Jewish0.000100.000099rare
East Asian0.0000550.000054rare
Finnish00.0absent
European (Non-Finnish)0.0000700.000070rare
South Asian00.0absent
Other0.000160.00016rare

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). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1. {ECO:0000269|PubMed:12097147, ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}.;

Recessive Scores

pRec
0.296

Intolerance Scores

LoFtool
0.749
RVIS EVS
-0.05
RVIS percentile EVS
49.76

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.756

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.