PSME4

proteasome activator subunit 4, the group of Armadillo like helical domain containing|Proteasome

Basic information

Region (hg38): 2:53864069-53970993

Links

ENSG00000068878 ∙ NCBI:23198 ∙ OMIM:607705 ∙ HGNC:20635 ∙ Uniprot:Q14997 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PSME4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSME4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3		3
missense			63	1		64
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	63	4	0

Variants in PSME4

This is a list of pathogenic ClinVar variants found in the PSME4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-53866223-T-C		not specified	Uncertain significance (Oct 03, 2022)
2-53866872-T-G		not specified	Uncertain significance (May 06, 2024)
2-53866876-C-A		not specified	Uncertain significance (Feb 28, 2023)
2-53874403-T-C		not specified	Uncertain significance (Jan 26, 2022)
2-53874412-A-C		not specified	Uncertain significance (Jul 13, 2022)
2-53874436-A-G		not specified	Uncertain significance (Nov 13, 2023)
2-53874482-T-C		not specified	Uncertain significance (Jan 16, 2024)
2-53887291-T-C		not specified	Uncertain significance (Jul 05, 2023)
2-53887295-C-A		not specified	Uncertain significance (Jan 16, 2024)
2-53887443-T-C		not specified	Uncertain significance (Jun 17, 2022)
2-53887894-G-A		not specified	Uncertain significance (Apr 23, 2024)
2-53888773-G-T		not specified	Uncertain significance (May 30, 2024)
2-53890119-A-G		EBV-positive nodal T- and NK-cell lymphoma	Likely benign (-)
2-53890132-T-C		not specified	Uncertain significance (Apr 19, 2023)
2-53890148-C-A		not specified	Uncertain significance (Mar 28, 2024)
2-53890201-T-G		not specified	Uncertain significance (Apr 04, 2023)
2-53892811-T-A		not specified	Uncertain significance (Dec 21, 2023)
2-53893690-C-T		not specified	Uncertain significance (Sep 20, 2023)
2-53893693-C-T		not specified	Uncertain significance (Mar 28, 2024)
2-53895054-C-T		not specified	Uncertain significance (Feb 10, 2023)
2-53895596-A-G		not specified	Uncertain significance (Aug 04, 2023)
2-53895644-T-C		not specified	Uncertain significance (Aug 20, 2023)
2-53895659-T-C		not specified	Uncertain significance (Jun 22, 2023)
2-53896815-G-A		not specified	Uncertain significance (Dec 27, 2022)
2-53896833-T-C		not specified	Uncertain significance (May 07, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSME4	protein_coding	protein_coding	ENST00000404125	46	106774

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.20e-10	125725	0	22	125747	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.27	757	954	0.793	0.0000474	12080
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.000110	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000133	0.000123
Middle Eastern	0.000110	0.000109
South Asian	0.0000994	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Proteasome - Homo sapiens (human);Post-translational protein modification;Metabolism of proteins;UCH proteinases;Neddylation;Ub-specific processing proteases;Deubiquitination (Consensus)

Recessive Scores

• pRec: 0.219

Intolerance Scores

• loftool: 0.450
• rvis_EVS: -1.05
• rvis_percentile_EVS: 7.6

Haploinsufficiency Scores

• pHI: 0.735
• hipred: Y
• hipred_score: 0.756
• ghis: 0.582

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.595

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Psme4
• Phenotype: cellular phenotype; reproductive system phenotype

Gene ontology

• Biological process: DNA repair;cellular response to DNA damage stimulus;multicellular organism development;proteasomal ubiquitin-independent protein catabolic process;positive regulation of peptidase activity;protein deubiquitination;spermatogenesis, exchange of chromosomal proteins;post-translational protein modification
• Cellular component: nucleus;nucleoplasm;cytosol;nuclear speck;spermatoproteasome complex
• Molecular function: protein binding;peptidase activator activity;lysine-acetylated histone binding;proteasome binding