PSME2

protein-coding

proteasome activator subunit 2, the group of Proteasome|MicroRNA protein coding host genes

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. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. The immunoproteasome contains an alternate regulator, referred to as the 11S regulator or PA28, that replaces the 19S regulator. Three subunits (alpha, beta and gamma) of the 11S regulator have been identified. This gene encodes the beta subunit of the 11S regulator, one of the two 11S subunits that is induced by gamma-interferon. Three beta and three alpha subunits combine to form a heterohexameric ring. Six pseudogenes have been identified on chromosomes 4, 5, 8, 10 and 13. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002818.3

Inheritance

—

ClinVar variants

U:37B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr14:24,143,362-24,147,570

External References & Databases

Ensembl (ENSG00000100911)

Transcript & Mutation Effects

hg38 • Region Span ~4.2 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 PSME2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 25

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002818.3. 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 clinvar	2
missense			28 clinvar	1 clinvar		29
nonsense						0
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	37	1	2	40

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 70 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002818.3	RefSeq	NP_002809.2	11	MANE Select
ENST00000216802.10	Ensembl	ENSP00000216802.5	11	MANE Select
ENST00000558273.5	Ensembl	ENSP00000453195.1	3	Standard
ENST00000559056.5	Ensembl	ENSP00000452940.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Antigen processing and presentation - Homo sapiens (human)
Proteasome - Homo sapiens (human)
Proteasome Degradation
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
Post-translational protein modification

Biological Process

positive regulation of endopeptidase activity
protein deubiquitination
interleukin-12-mediated signaling pathway
post-translational protein modification
regulation of proteasomal protein catabolic process

Molecular Function

protein binding
identical protein binding
endopeptidase activator activity

Cellular Component

proteasome complex
nucleoplasm
cytoplasm
cytosol
proteasome activator complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000216802
Coding exons: 11
Length: 4206
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 125748
p: 0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.22	88	127	0.695	0.00000621	1566
Missense (PolyPhen)		13	34.654	0.37514		517
Synonymous	1.89	30	46.3	0.647	0.00000213	434
Loss of Function	2.47	6	17.0	0.353	8.07e-7	204

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Implicated in immunoproteasome assembly and required for efficient antigen processing. The PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern of the proteasome.;

Recessive Scores

pRec: 0.173

Intolerance Scores

LoFtool: 0.657
RVIS EVS: 0.1
RVIS percentile EVS: 61.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.961

Gene Damage Prediction

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