PSMD5

protein-coding

proteasome 26S subunit, non-ATPase 5, the group of Proteasome|Armadillo like helical domain containing

Gene summary

The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. This gene encodes a non-ATPase subunit of the 19S regulator base that functions as a chaperone protein during 26S proteasome assembly. [provided by RefSeq, Jul 2012]

MANE transcript

NM_005047.4

Inheritance

—

ClinVar variants

U:74B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr9:120,815,496-120,842,951

External References & Databases

Ensembl (ENSG00000095261)

Transcript & Mutation Effects

hg38 • Region Span ~27.5 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 PSMD5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 70

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005047.4. 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			3 clinvar			3
missense			71 clinvar	2 clinvar		73
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	74	2	0	76

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005047.4	RefSeq	NP_005038.1	10	MANE Select
ENST00000210313.8	Ensembl	ENSP00000210313.2	10	MANE Select
NM_001270427.2	RefSeq	NP_001257356.1	9	Standard
ENST00000373904.5	Ensembl	ENSP00000363011.5	9	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

protein deubiquitination
post-translational protein modification
proteasome regulatory particle assembly

Molecular Function

protein binding

Cellular Component

proteasome complex
nucleoplasm
cytosol
proteasome regulatory particle, base subcomplex
proteasome accessory complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000210313
Coding exons: 10
Length: 27489
Individuals with no LoFs: 125680
Homozygous LoFs: 0
Heterozygous LoFs: 66
Defined: 125746
p: 0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.287	255	268	0.951	0.0000135	3235
Missense (PolyPhen)		138	141.32	0.97651		1791
Synonymous	0.559	93	100	0.929	0.00000475	1020
Loss of Function	1.43	15	22.3	0.674	0.00000108	290

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00083	0.00078	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00041	0.00038	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00024	0.00024	rare
South Asian	0.000068	0.000065	rare
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 base subcomplex of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD5:PSMC2:PSMC1:PSMD2 module which probably assembles with a PSMD10:PSMC4:PSMC5:PAAF1 module followed by dissociation of PSMD5. {ECO:0000269|PubMed:19412159, ECO:0000269|PubMed:19490896}.;

Recessive Scores

pRec: 0.132

Intolerance Scores

LoFtool: 0.721
RVIS EVS: -0.2
RVIS percentile EVS: 38.98

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.967

Gene Damage Prediction

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