PSMC4

proteasome 26S subunit, ATPase 4, the group of AAA ATPases|Proteasome

Basic information

Region (hg38): 19:39971164-39981764

Previous symbols: [ "MIP224" ]

Links

ENSG00000013275 ∙ NCBI:5704 ∙ OMIM:602707 ∙ HGNC:9551 ∙ Uniprot:P43686 ∙ 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 PSMC4 gene.

• Inborn genetic diseases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSMC4 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						0
missense			2			2
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	2	0	0

Variants in PSMC4

This is a list of pathogenic ClinVar variants found in the PSMC4 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-39972170-T-G		not specified	Uncertain significance (Oct 05, 2023)
19-39972181-G-T		not specified	Uncertain significance (Oct 05, 2023)
19-39974536-A-G		not specified	Uncertain significance (Sep 30, 2021)
19-39974568-A-G		not specified	Uncertain significance (Jan 24, 2024)
19-39974611-C-T		not specified	Uncertain significance (Feb 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSMC4	protein_coding	protein_coding	ENST00000157812	11	10437

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.301	0.699	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.53	105	268	0.392	0.0000170	2746
Missense in Polyphen		15	101.35	0.148		949
Synonymous	-0.0891	105	104	1.01	0.00000647	808
Loss of Function	3.28	5	21.3	0.234	0.00000108	248

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000154	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000706	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC4 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. {ECO:0000269|PubMed:1317798, ECO:0000269|PubMed:8060531}.
• Pathway: Epstein-Barr virus infection - Homo sapiens (human);Proteasome - Homo sapiens (human);Proteasome Degradation;Parkin-Ubiquitin Proteasomal System pathway;TLR NFkB;regulation of eif-4e and p70s6 kinase;skeletal muscle hypertrophy is regulated via akt-mtor pathway;B cell receptor signaling;Post-translational protein modification;Metabolism of proteins;DroToll-like;Notch;Hedgehog;IL-1 NFkB;IL-1 p38;IL-1 JNK;TGF-beta super family signaling pathway canonical;TLR p38;UCH proteinases;Neddylation;Ub-specific processing proteases;JAK STAT pathway and regulation;Deubiquitination;TLR JNK;TNF;Wnt Canonical;Wnt Mammals;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.388

Intolerance Scores

• loftool: 0.241
• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.31

Haploinsufficiency Scores

• pHI: 0.431
• hipred: Y
• hipred_score: 0.774
• ghis: 0.644

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.952

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Psmc4
• Phenotype: growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton phenotype

Gene ontology

• Biological process: blastocyst development;proteolysis;protein deubiquitination;protein catabolic process;post-translational protein modification;positive regulation of RNA polymerase II transcriptional preinitiation complex assembly;positive regulation of proteasomal protein catabolic process
• Cellular component: proteasome complex;nucleus;nucleoplasm;cytosol;proteasome regulatory particle, base subcomplex;membrane;inclusion body;proteasome accessory complex;cytosolic proteasome complex;synapse
• Molecular function: protein binding;ATP binding;ATPase activity;proteasome-activating ATPase activity