PSMC3
proteasome 26S subunit, ATPase 3, the group of Proteasome|AAA ATPases
Basic information
Region (hg38): 11:47418769-47426473
Links
Phenotypes
GenCC
Source:
- complex neurodevelopmental disorder (Strong), mode of inheritance: AD
- deafness, cataract, impaired intellectual development, and polyneuropathy (Limited), mode of inheritance: AR
- neurodevelopmental disorder (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
| 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
- not_provided (23 variants)
- Inborn_genetic_diseases (18 variants)
- Neurodevelopmental_disorder (2 variants)
- Developmental_dysplasia_of_the_hip (1 variants)
- Deafness,_cataract,_impaired_intellectual_development,_and_polyneuropathy (1 variants)
- Developmental_cataract (1 variants)
- Polymicrogyria (1 variants)
- Cerebellar_vermis_hypoplasia (1 variants)
- Global_developmental_delay (1 variants)
- Neurodevelopmental_delay (1 variants)
- Microcephaly (1 variants)
- Atrial_septal_defect,_ostium_secundum_type (1 variants)
- Abnormality_of_the_pulmonary_veins (1 variants)
- Patent_ductus_arteriosus (1 variants)
- Microretrognathia (1 variants)
- High_anterior_hairline (1 variants)
- Patent_foramen_ovale (1 variants)
- PSMC3-Related_Neurodevelopmental_Delay (1 variants)
- Severe_sensorineural_hearing_impairment (1 variants)
- Failure_to_thrive (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. These statistics are base on transcript: NM_000002804.5. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 8 | |||||
| missense | 28 | 34 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 3 | 3 | 29 | 8 | 0 |
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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