PSMC2

proteasome 26S subunit, ATPase 2, the group of AAA ATPases|Proteasome

Basic information

Region (hg38): 7:103328570-103370346

Links

ENSG00000161057 ∙ NCBI:5701 ∙ OMIM:154365 ∙ HGNC:9548 ∙ Uniprot:P35998 ∙ 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 PSMC2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSMC2 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				2		2
missense			7			7
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2	1	2	5
Total	0	0	10	3	2

Variants in PSMC2

This is a list of pathogenic ClinVar variants found in the PSMC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-103337754-T-C		not specified	Uncertain significance (Jun 05, 2023)
7-103341877-C-T		not specified	Uncertain significance (Mar 01, 2023)
7-103341891-T-C		not specified	Uncertain significance (Mar 16, 2024)
7-103352579-A-G			Benign (Mar 31, 2019)
7-103352638-C-T			Benign (Dec 12, 2018)
7-103352648-G-T			Likely benign (Dec 23, 2018)
7-103354878-C-G		not specified	Uncertain significance (Jun 30, 2022)
7-103354913-A-T		not specified	Uncertain significance (Apr 19, 2023)
7-103354946-A-G		not specified	Uncertain significance (Dec 22, 2023)
7-103361968-T-C		not specified	Uncertain significance (Jan 27, 2022)
7-103361991-C-T			Uncertain significance (Apr 04, 2023)
7-103362026-G-GT			Uncertain significance (Feb 01, 2020)
7-103363349-A-G			Likely benign (Dec 01, 2022)
7-103364302-G-T			Uncertain significance (Aug 28, 2020)
7-103367599-G-A		not specified	Uncertain significance (Sep 25, 2023)
7-103367944-A-C			Likely benign (Apr 01, 2022)
7-103367986-G-T		not specified	Uncertain significance (May 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSMC2	protein_coding	protein_coding	ENST00000435765	12	25142

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000150	125738	0	4	125742	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.62	90	252	0.358	0.0000134	2864
Missense in Polyphen		23	129.42	0.17772		1418
Synonymous	0.480	81	86.7	0.934	0.00000472	806
Loss of Function	4.64	0	25.1	0.00	0.00000146	275

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000601	0.0000601
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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. PSMC2 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:9295362}.
• Pathway: Epstein-Barr virus infection - Homo sapiens (human);Proteasome - Homo sapiens (human);Proteasome Degradation;Parkin-Ubiquitin Proteasomal System pathway;TLR NFkB;Neutrophil degranulation;B cell receptor signaling;Post-translational protein modification;Metabolism of proteins;DroToll-like;Notch;Hedgehog;Innate Immune System;Immune System;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;TNFalpha;TLR JNK;TNF;Wnt Canonical;Wnt Mammals;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Intolerance Scores

• rvis_EVS: -0.27
• rvis_percentile_EVS: 33.97

Haploinsufficiency Scores

• pHI: 0.860
• hipred: Y
• hipred_score: 0.831
• ghis: 0.609

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.993

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Psmc2

Zebrafish Information Network

• Gene name: psmc2
• Affected structure: lens
• Phenotype tag: abnormal
• Phenotype quality: mislocalised anteriorly

Gene ontology

• Biological process: osteoblast differentiation;ubiquitin-dependent protein catabolic process;protein deubiquitination;neutrophil degranulation;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;P-body;extracellular region;nucleus;nucleoplasm;cytoplasm;cytosol;proteasome regulatory particle, base subcomplex;membrane;proteasome accessory complex;secretory granule lumen;cytoplasmic ribonucleoprotein granule;dendritic spine;ficolin-1-rich granule lumen
• Molecular function: protein binding;ATP binding;ATPase activity;TBP-class protein binding;proteasome-activating ATPase activity