PSMA1
protein-codingproteasome 20S subunit alpha 1, 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 peptidase T1A family, that is a 20S core alpha subunit. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Jan 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~139.4 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 PSMA1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002786.4. 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 | 1 | 1 | ||||
| missense | 14 | 14 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 15 | 1 | 1 | 17 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002777.1 | 10 | MANE Select | |
| Ensembl | ENSP00000379676.2 | 10 | MANE Select | |
| RefSeq | NP_001137409.1 | 5 | Standard | |
| RefSeq | NP_683877.1 | 10 | 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
- immune system process
- proteasomal protein catabolic process
- proteasomal ubiquitin-independent protein catabolic process
- protein deubiquitination
- proteasome-mediated ubiquitin-dependent protein catabolic process
Molecular Function
- RNA binding
- endopeptidase activity
- threonine-type endopeptidase activity
- protein binding
Cellular Component
- proteasome complex
- nucleus
- nucleoplasm
- cytoplasm
- centrosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000418988
- Coding exons
- 10
- Length
- 149853
- Individuals with no LoFs
- 120825
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 213
- Defined
- 121040
- p
- 0.000889
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.89 | 79 | 142 | 0.555 | 0.00000724 | 1747 |
| Missense (PolyPhen) | 9 | 41.399 | 0.2174 | 548 | ||
| Synonymous | -0.535 | 52 | 47.3 | 1.10 | 0.00000235 | 514 |
| Loss of Function | 3.56 | 1 | 16.7 | 0.0598 | 8.57e-7 | 209 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0090 | 0.0089 | notable |
| Latino/Admixed American | 0.00051 | 0.00046 | rare |
| Ashkenazi Jewish | 0.0049 | 0.0048 | notable |
| East Asian | 0.000057 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000093 | 0.000090 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00017 | 0.00017 | rare |
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
- 0.506
Intolerance Scores
- LoFtool
- 0.282
- RVIS EVS
- -0.23
- RVIS percentile EVS
- 36.86
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |