PSMD6
protein-codingproteasome 26S subunit, non-ATPase 6, the group of Proteasome
Gene summary
This gene encodes a member of the protease subunit S10 family. The encoded protein is a subunit of the 26S proteasome which colocalizes with DNA damage foci and is involved in the ATP-dependent degradation of ubiquinated proteins. Alternative splicing results in multiple transcript variants [provided by RefSeq, Nov 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.5 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 PSMD6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014814.3. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 3 | |||
| missense | 44 | 44 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 50 | 1 | 0 | 51 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055629.1 | 8 | MANE Select | |
| Ensembl | ENSP00000295901.4 | 8 | MANE Select | |
| RefSeq | NP_001258708.1 | 9 | Standard | |
| RefSeq | NP_001258709.1 | 8 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| psmd6 | Danio rerio | Structure: midbrain hindbrain boundary Quality: hemorrhagic abnormal |
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)
- Proteasome Degradation
- Parkin-Ubiquitin Proteasomal System pathway
- TLR NFkB
Biological Process
- proteolysis
- protein deubiquitination
- proteasome-mediated ubiquitin-dependent protein catabolic process
- neutrophil degranulation
- post-translational protein modification
Molecular Function
- protein binding
- ATPase activity
- enzyme regulator activity
Cellular Component
- proteasome complex
- extracellular region
- nucleoplasm
- cytosol
- proteasome regulatory particle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000295901
- Coding exons
- 8
- Length
- 13434
- Individuals with no LoFs
- 125675
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125685
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.26 | 163 | 215 | 0.759 | 0.0000112 | 2542 |
| Missense (PolyPhen) | 41 | 76.848 | 0.53352 | 961 | ||
| Synonymous | -1.08 | 91 | 78.8 | 1.15 | 0.00000397 | 728 |
| Loss of Function | 3.96 | 1 | 20.2 | 0.0495 | 0.00000110 | 255 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000063 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000071 | 0.000070 | 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. {ECO:0000269|PubMed:1317798}.;
Recessive Scores
- pRec
- 0.159
Intolerance Scores
- LoFtool
- 0.106
- RVIS EVS
- -0.6
- RVIS percentile EVS
- 17.91
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.846
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |