PSMC3

proteasome 26S subunit, ATPase 3, the group of Proteasome|AAA ATPases

Basic information

Region (hg38): 11:47418769-47426473

Links

ENSG00000165916 ∙ NCBI:5702 ∙ OMIM:186852 ∙ HGNC:9549 ∙ Uniprot:P17980 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Strong), mode of inheritance: AD
• deafness, cataract, impaired intellectual development, and polyneuropathy (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, cataract, impaired intellectual development, and polyneuropathy	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Musculoskeletal; Neurologic; Ophthalmologic	32500975
Cochlear implants were not described as effective

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PSMC3 gene.

• 12 conditions (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSMC3 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				6		6
missense	1	1	8			10
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	1	1	8	6	0

Variants in PSMC3

This is a list of pathogenic ClinVar variants found in the PSMC3 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-47418904-G-A			Likely benign (Sep 01, 2023)
11-47419121-C-G			Uncertain significance (Feb 09, 2023)
11-47419927-T-C		Severe sensorineural hearing impairment;Neurodevelopmental delay;Developmental cataract • Deafness, cataract, impaired intellectual development, and polyneuropathy	Pathogenic (Jun 01, 2021)
11-47420326-C-T			Likely benign (Mar 01, 2024)
11-47420351-C-T			Uncertain significance (Mar 10, 2022)
11-47420377-C-T			Likely benign (Nov 01, 2022)
11-47420683-A-G		Inborn genetic diseases	Likely pathogenic (Mar 11, 2024)
11-47420702-G-A		12 conditions	Pathogenic (Apr 14, 2022)
11-47420702-G-C		PSMC3-Related Neurodevelopmental Delay	Pathogenic (Oct 12, 2024)
11-47422585-G-C			Uncertain significance (Apr 11, 2023)
11-47422604-A-G		Inborn genetic diseases	Uncertain significance (Apr 18, 2023)
11-47422632-T-C			Uncertain significance (Dec 02, 2023)
11-47422676-A-G			Uncertain significance (Apr 28, 2022)
11-47422703-G-A			Uncertain significance (Feb 22, 2022)
11-47422842-G-A			Likely benign (Dec 01, 2023)
11-47422853-G-A			Uncertain significance (Aug 16, 2023)
11-47424080-C-T			Uncertain significance (Feb 15, 2023)
11-47424489-C-T			Likely benign (Jul 01, 2024)
11-47424666-T-C		Inborn genetic diseases	Uncertain significance (Sep 26, 2023)
11-47425130-G-A			Likely benign (Nov 01, 2021)
11-47425913-G-A			Uncertain significance (Mar 12, 2024)
11-47425931-T-C			Uncertain significance (Nov 16, 2023)
11-47426227-G-A		Inborn genetic diseases	Uncertain significance (May 07, 2024)
11-47426262-A-G			Likely benign (Sep 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSMC3	protein_coding	protein_coding	ENST00000298852	12	7674

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.955	0.0453	125743	0	5	125748	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.87	85	261	0.326	0.0000149	2885
Missense in Polyphen		18	89.808	0.20043		939
Synonymous	0.623	97	105	0.923	0.00000634	835
Loss of Function	3.86	3	22.9	0.131	0.00000116	262

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
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. PSMC3 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}.
• 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)

Recessive Scores

• pRec: 0.399

Intolerance Scores

• loftool: 0.115
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.04

Haploinsufficiency Scores

• pHI: 0.992
• hipred: Y
• hipred_score: 0.783
• ghis: 0.667

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.982

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Psmc3
• Phenotype: embryo 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); reproductive system phenotype

Gene ontology

• Biological process: blastocyst development;viral process;protein deubiquitination;protein catabolic process;neutrophil degranulation;post-translational protein modification;modulation by host of viral transcription;positive regulation of RNA polymerase II transcriptional preinitiation complex assembly;positive regulation of transcription by RNA polymerase II;positive regulation of proteasomal protein catabolic process
• Cellular component: proteasome complex;P-body;extracellular region;nucleus;nucleoplasm;cytosol;proteasome regulatory particle, base subcomplex;membrane;proteasome accessory complex;secretory granule lumen;ficolin-1-rich granule lumen
• Molecular function: protein binding;ATP binding;ATPase activity;proteasome-activating ATPase activity;identical protein binding