PSMA8

protein-coding

proteasome 20S subunit alpha 8, the group of Proteasome

Gene summary

Predicted to be involved in meiotic cell cycle and proteasome-mediated ubiquitin-dependent protein catabolic process. Located in extracellular exosome and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001025096.2

Inheritance

—

ClinVar variants

U:37

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr18:26,133,852-26,193,355

External References & Databases

Ensembl (ENSG00000154611)

Transcript & Mutation Effects

hg38 • Region Span ~59.5 kb

Loading mutation effect viewer...

GenCC 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 PSMA8 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 38

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001025096.2. 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						0
missense			36 clinvar			36
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	37	0	0	37

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001025096.2	RefSeq	NP_001020267.1	7	MANE Select
ENST00000415576.7	Ensembl	ENSP00000409284.2	7	MANE Select
NM_001025097.2	RefSeq	NP_001020268.1	7	Standard
NM_001308188.2	RefSeq	NP_001295117.1	7	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

proteasomal protein catabolic process
proteasomal ubiquitin-independent protein catabolic process
protein deubiquitination
proteasome-mediated ubiquitin-dependent protein catabolic process
post-translational protein modification

Molecular Function

endopeptidase activity
threonine-type endopeptidase activity

Cellular Component

nucleus
cytoplasm
cytosol
proteasome core complex
proteasome core complex, alpha-subunit complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000308268
Coding exons: 7
Length: 59504
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 32
Defined: 125748
p: 0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.368	126	138	0.912	0.00000721	1654
Missense (PolyPhen)		70	74.17	0.94378		876
Synonymous	-0.122	48	46.9	1.02	0.00000253	494
Loss of Function	1.49	9	15.3	0.588	0.00000103	161

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00017	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the spermatoproteasome, a form of the proteasome specifically found in testis that promotes degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis. The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.142

Intolerance Scores

LoFtool: 0.630
RVIS EVS: -0.14
RVIS percentile EVS: 43.29

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.798

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium