PSMC1

proteasome 26S subunit, ATPase 1, the group of Proteasome|AAA ATPases

Basic information

Region (hg38): 14:90256526-90275429

Links

ENSG00000100764 ∙ NCBI:5700 ∙ OMIM:602706 ∙ HGNC:9547 ∙ Uniprot:P62191 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss (Limited), mode of inheritance: AR
• neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Birk-Aharoni syndrome (Neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss)	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; Craniofacial; Endocrine; Genitourinary; Hematologic; Musculoskeletal; Neurologic	35861243

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PSMC1 gene.

• not provided (2 variants)
• Inborn genetic diseases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSMC1 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			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	2

Variants in PSMC1

This is a list of pathogenic ClinVar variants found in the PSMC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-90263394-A-G			Benign (Dec 31, 2019)
14-90263450-G-A		Malignant tumor of prostate	Uncertain significance (-)
14-90263727-C-T			Benign (Aug 17, 2021)
14-90265070-G-C		not specified	Uncertain significance (Jan 31, 2024)
14-90268235-T-A		not specified	Uncertain significance (Jun 27, 2022)
14-90269498-T-C		Neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss	Pathogenic (Jun 09, 2023)
14-90270221-T-C		not specified	Uncertain significance (Sep 16, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSMC1	protein_coding	protein_coding	ENST00000261303	11	16130

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000553	125709	0	4	125713	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.95	66	237	0.278	0.0000123	2885
Missense in Polyphen		10	58.65	0.1705		756
Synonymous	0.350	83	87.2	0.952	0.00000479	838
Loss of Function	4.31	0	21.6	0.00	0.00000117	284

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000362	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000332	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. PSMC1 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: Viral carcinogenesis - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Proteasome - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Proteasome Degradation;Parkin-Ubiquitin Proteasomal System pathway;TLR NFkB;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;Asparagine N-linked glycosylation;Neddylation;Ub-specific processing proteases;JAK STAT pathway and regulation;Deubiquitination;TNFalpha;TLR JNK;N-glycan trimming in the ER and Calnexin/Calreticulin cycle;TNF;Wnt Canonical;Wnt Mammals;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Intolerance Scores

• loftool: 0.280
• rvis_EVS: -0.3
• rvis_percentile_EVS: 32.62

Haploinsufficiency Scores

• pHI: 0.858
• hipred: Y
• hipred_score: 0.783
• ghis: 0.647

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Psmc1
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); 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)

Gene ontology

• Biological process: protein folding;protein deubiquitination;protein catabolic process;post-translational protein modification;negative regulation of neuron death;positive regulation of proteasomal protein catabolic process
• Cellular component: proteasome complex;nucleus;nucleoplasm;cytosol;proteasome regulatory particle, base subcomplex;membrane;proteasome accessory complex
• Molecular function: RNA binding;protein binding;ATP binding;ATPase activity;TBP-class protein binding;proteasome-activating ATPase activity