PSMA4
protein-codingproteasome 20S subunit alpha 4, the group of Proteasome
Gene summary
This gene encodes a core alpha subunit of the 20S proteosome, which is a highly ordered ring-shaped structure composed of four rings of 28 non-identical subunits. Proteasomes cleave peptides in an ATP- and ubiquitin-dependent manner. [provided by RefSeq, Aug 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.0 kbGenCC 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 PSMA4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002789.6. 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 | 1 | 1 | 1 | 3 | ||
| missense | 13 | 13 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 18 | 1 | 1 | 20 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002780.1 | 8 | MANE Select | |
| Ensembl | ENSP00000044462.7 | 8 | MANE Select | |
| RefSeq | NP_001096137.1 | 8 | Standard | |
| RefSeq | NP_001096138.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Proteasome - Homo sapiens (human)
- Proteasome Degradation
- Exercise-induced Circadian Regulation
- TLR NFkB
- proteasome complex
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
- P-body
- nucleus
- nucleoplasm
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000044462
- Coding exons
- 8
- Length
- 8858
- Individuals with no LoFs
- 125717
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125722
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.44 | 57 | 138 | 0.414 | 0.00000687 | 1704 |
| Missense (PolyPhen) | 13 | 58.353 | 0.22278 | 711 | ||
| Synonymous | 0.795 | 38 | 44.8 | 0.849 | 0.00000211 | 462 |
| Loss of Function | 2.99 | 3 | 15.9 | 0.189 | 7.31e-7 | 208 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000059 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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
- 0.388
Intolerance Scores
- LoFtool
- 0.388
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 46.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.792
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |