PSMD10

protein-coding

proteasome 26S subunit, non-ATPase 10, the group of Ankyrin repeat domain containing|Proteasome

Gene summary

This gene encodes a subunit of the PA700/19S complex, which is the regulatory component of the 26S proteasome. The 26S proteosome complex is required for ubiquitin-dependent protein degradation. This protein is a non-ATPase subunit that may be involved in protein-protein interactions. Aberrant expression of this gene may paly a role in tumorigenesis. Two transcripts encoding different isoforms have been described. Pseudogenes have been identified on chromosomes 3 and 20.[provided by RefSeq, Mar 2011]

MANE transcript

NM_002814.4

Inheritance

—

ClinVar variants

U:67B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chrX:108,084,207-108,091,549

External References & Databases

Ensembl (ENSG00000101843)

Transcript & Mutation Effects

hg38 • Region Span ~7.3 kb

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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 PSMD10 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 12

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002814.4. 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			11 clinvar	1 clinvar	1 clinvar	13
missense			39 clinvar		1 clinvar	40
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			14 clinvar			14
Total	0	0	67	1	2	70

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002814.4	RefSeq	NP_002805.1	5	MANE Select
ENST00000217958.8	Ensembl	ENSP00000217958.3	5	MANE Select
NM_170750.3	RefSeq	NP_736606.1	5	Standard
ENST00000340200.5	Ensembl	ENSP00000345963.5	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Proteasome Degradation
Parkin-Ubiquitin Proteasomal System pathway
TLR NFkB
B cell receptor signaling
Post-translational protein modification

Biological Process

negative regulation of transcription by RNA polymerase II
apoptotic process
cytoplasmic sequestering of NF-kappaB
protein deubiquitination
positive regulation of cell growth

Molecular Function

protein binding
transcription factor binding

Cellular Component

proteasome complex
nucleus
nucleoplasm
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000217958
Coding exons: 5
Length: 7412
Individuals with no LoFs: 125743
Homozygous LoFs: 3
Heterozygous LoFs: 0
Defined: 125746
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.883	60	82.6	0.727	0.00000578	1471
Missense (PolyPhen)		12	26.291	0.45643		486
Synonymous	0.323	30	32.3	0.928	0.00000235	445
Loss of Function	1.91	1	6.07	0.165	3.80e-7	128

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000072	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000024	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a chaperone during the assembly of the 26S proteasome, specifically of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module. Independently of the proteasome, regulates EGF-induced AKT activation through inhibition of the RHOA/ROCK/PTEN pathway, leading to prolonged AKT activation. Plays an important role in RAS-induced tumorigenesis.;

Recessive Scores

pRec: 0.125

Intolerance Scores

LoFtool: 0.391
RVIS EVS: -0.1
RVIS percentile EVS: 46.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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