PSMC1
Basic information
Region (hg38): 14:90256527-90275429
Links
Phenotypes
GenCC
Source:
- 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:
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
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 | |||||
missense | 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) | |||
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:
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:
- 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