PSME4
protein-codingproteasome activator subunit 4, the group of Armadillo like helical domain containing|Proteasome
Gene summary
Predicted to enable peptidase activator activity. Predicted to be involved in DNA repair; proteasomal ubiquitin-independent protein catabolic process; and sperm DNA condensation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~106.9 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 PSME4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014614.3. 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 | 7 | 5 | 12 | |||
| missense | 203 | 2 | 205 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 218 | 7 | 0 | 225 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055429.2 | 46 | MANE Select | |
| Ensembl | ENSP00000384211.1 | 46 | MANE Select | |
| Ensembl | ENSP00000374643.3 | 14 | Standard | |
| Ensembl | ENSP00000548924.1 | 46 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Proteasome - Homo sapiens (human)
- Post-translational protein modification
- Metabolism of proteins
- UCH proteinases
- Neddylation
Biological Process
- DNA repair
- cellular response to DNA damage stimulus
- multicellular organism development
- proteasomal ubiquitin-independent protein catabolic process
- positive regulation of peptidase activity
Molecular Function
- protein binding
- peptidase activator activity
- lysine-acetylated histone binding
- proteasome binding
Cellular Component
- nucleus
- nucleoplasm
- cytosol
- nuclear speck
- spermatoproteasome complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000404125
- Coding exons
- 46
- Length
- 106774
- Individuals with no LoFs
- 125725
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 125747
- p
- 0.0000875
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.27 | 757 | 954 | 0.793 | 0.0000474 | 12080 |
| Missense (PolyPhen) | 102 | 201.04 | 0.50736 | 2577 | ||
| Synonymous | -1.29 | 369 | 339 | 1.09 | 0.0000166 | 3464 |
| Loss of Function | 8.89 | 13 | 117 | 0.111 | 0.00000670 | 1340 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00013 | 0.00012 | rare |
| South Asian | 0.000099 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Associated component of the proteasome that specifically recognizes acetylated histones and promotes ATP- and ubiquitin- independent degradation of core histones during spermatogenesis and DNA damage response. Recognizes and binds acetylated histones via its bromodomain-like (BRDL) region and activates the proteasome by opening the gated channel for substrate entry. Binds to the core proteasome via its C-terminus, which occupies the same binding sites as the proteasomal ATPases, opening the closed structure of the proteasome via an active gating mechanism. Component of the spermatoproteasome, a form of the proteasome specifically found in testis: binds to acetylated histones and promotes degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis. Also involved in DNA damage response in somatic cells, by promoting degradation of histones following DNA double-strand breaks. {ECO:0000269|PubMed:12093752, ECO:0000269|PubMed:18845680, ECO:0000269|PubMed:22550082, ECO:0000269|PubMed:23706739}.;
Recessive Scores
- pRec
- 0.219
Intolerance Scores
- LoFtool
- 0.450
- RVIS EVS
- -1.05
- RVIS percentile EVS
- 7.6
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.595
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | High | Medium | High |
| Cancer | High | Medium | High |