PSMC1

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

Basic information

Region (hg38): 14:90256527-90275429

Links

ENSG00000100764NCBI:5700OMIM:602706HGNC:9547Uniprot:P62191AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Birk-Aharoni syndrome (Neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss)ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingAudiologic/Otolaryngologic; Craniofacial; Endocrine; Genitourinary; Hematologic; Musculoskeletal; Neurologic35861243

ClinVar

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

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
clinvar
2
missense
3
clinvar
3
nonsense
0
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
0
non coding
0
Total 0 0 3 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)770241
14-90263450-G-A Malignant tumor of prostate Uncertain significance (-)161600
14-90263727-C-T Benign (Aug 17, 2021)1302301
14-90265070-G-C not specified Uncertain significance (Jan 31, 2024)3220398
14-90268235-T-A not specified Uncertain significance (Jun 27, 2022)2297861
14-90269498-T-C Neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss Pathogenic (Jun 09, 2023)1710322
14-90270221-T-C not specified Uncertain significance (Sep 16, 2021)2250640

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PSMC1protein_codingprotein_codingENST00000261303 1116130
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9990.000553125709041257130.0000159
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense3.95662370.2780.00001232885
Missense in Polyphen1058.650.1705756
Synonymous0.3508387.20.9520.00000479838
Loss of Function4.31021.60.000.00000117284

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00003620.0000264
Middle Eastern0.000.00
South Asian0.00003320.0000327
Other0.000.00

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

AllRecessiveDominant
MendelianMediumLowLow
Primary ImmunodeficiencyMediumLowMedium
CancerMediumLowMedium

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