PSMD14
protein-codingproteasome 26S subunit, non-ATPase 14, the group of Proteasome|JAMM/MPN+ metallopeptidase family
Gene summary
This gene encodes a component of the 26S proteasome. The 26S proteasome is a large multiprotein complex that catalyzes the degradation of ubiquitinated intracellular proteins. The encoded protein is a component of the 19S regulatory cap complex of the 26S proteasome and mediates substrate deubiquitination. A pseudogene of this gene is also located on the long arm of chromosome 2. [provided by RefSeq, Feb 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~103.3 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 PSMD14 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005805.6. 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 | 2 | 1 | 3 | |||
| missense | 12 | 12 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 16 | 1 | 0 | 17 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005796.1 | 10 | MANE Select | |
| Ensembl | ENSP00000386541.3 | 10 | MANE Select | |
| Ensembl | ENSP00000399311.1 | 4 | Standard | |
| Ensembl | ENSP00000569727.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Epstein-Barr virus infection - Homo sapiens (human)
- Proteasome - Homo sapiens (human)
- Parkin-Ubiquitin Proteasomal System pathway
- Neutrophil degranulation
- proteasome complex
Biological Process
- double-strand break repair via homologous recombination
- double-strand break repair via nonhomologous end joining
- ubiquitin-dependent protein catabolic process
- positive regulation of endopeptidase activity
- protein deubiquitination
Molecular Function
- thiol-dependent ubiquitin-specific protease activity
- protein binding
- metallopeptidase activity
- thiol-dependent ubiquitinyl hydrolase activity
- metal ion binding
Cellular Component
- proteasome complex
- extracellular region
- nucleus
- nucleoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000409682
- Coding exons
- 10
- Length
- 103680
- Individuals with no LoFs
- 124563
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 124565
- p
- 0.00000803
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.57 | 29 | 153 | 0.189 | 0.00000735 | 2035 |
| Missense (PolyPhen) | 10 | 69.51 | 0.14386 | 901 | ||
| Synonymous | 1.46 | 37 | 50.1 | 0.738 | 0.00000247 | 550 |
| Loss of Function | 3.47 | 1 | 15.9 | 0.0627 | 6.76e-7 | 234 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000089 | 0.0000089 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. The PSMD14 subunit is a metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains within the complex. Plays a role in response to double-strand breaks (DSBs): acts as a regulator of non- homologous end joining (NHEJ) by cleaving 'Lys-63'-linked polyubiquitin, thereby promoting retention of JMJD2A/KDM4A on chromatin and restricting TP53BP1 accumulation. Also involved in homologous recombination repair by promoting RAD51 loading. {ECO:0000269|PubMed:1317798, ECO:0000269|PubMed:22909820, ECO:0000269|PubMed:9374539}.;
Recessive Scores
- pRec
- 0.281
Intolerance Scores
- LoFtool
- 0.369
- RVIS EVS
- 0.01
- RVIS percentile EVS
- 54.63
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.903
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |