PSMA3

proteasome 20S subunit alpha 3, the group of Proteasome

Basic information

Region (hg38): 14:58244843-58272012

Links

ENSG00000100567 ∙ NCBI:5684 ∙ OMIM:176843 ∙ HGNC:9532 ∙ Uniprot:P25788 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Proteasome-associated autoinflammatory syndrome 2	Digenic	Allergy/Immunology/Infectious	Individuals may have recurrent infections, and awareness may allow preventative measures as well as prompt and agressive treatment of infections	Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic	26524591
Digenic inheritance has been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PSMA3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSMA3 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			1	37	1	39
missense			52			52
nonsense						0
start loss						0
frameshift						0
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region			12	15	4	31
non coding			3	50	5	58
Total	0	0	58	87	6

Variants in PSMA3

This is a list of pathogenic ClinVar variants found in the PSMA3 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-58244926-C-T			Likely benign (Jul 26, 2023)
14-58244929-A-G			Likely benign (Sep 07, 2022)
14-58244935-C-T			Likely benign (May 12, 2023)
14-58244938-T-C			Likely benign (Dec 08, 2021)
14-58244953-G-C			Likely benign (Dec 08, 2023)
14-58247736-C-T			Likely benign (Jan 31, 2024)
14-58247743-C-T			Likely benign (Sep 18, 2023)
14-58247752-T-C			Likely benign (Aug 31, 2022)
14-58247763-C-T			Uncertain significance (Jun 19, 2022)
14-58247764-C-G			Likely benign (Jul 29, 2021)
14-58247767-T-C			Likely benign (Aug 10, 2023)
14-58247779-T-C			Likely benign (Feb 10, 2021)
14-58247782-C-T			Likely benign (Oct 11, 2022)
14-58247810-A-G			Uncertain significance (Oct 30, 2022)
14-58247822-G-A			Uncertain significance (Feb 19, 2022)
14-58247843-T-C			Likely benign (Jun 25, 2023)
14-58247846-AACCAGGTATT-A			Likely benign (Jul 17, 2023)
14-58247847-A-G			Likely benign (Nov 29, 2022)
14-58252100-TTTC-T			Likely benign (May 04, 2022)
14-58252101-T-A			Likely benign (Aug 17, 2023)
14-58252104-T-C			Likely benign (Aug 10, 2023)
14-58252105-TCTC-T			Likely benign (Dec 27, 2023)
14-58252108-CCTT-C			Likely benign (Jul 26, 2023)
14-58252141-A-G			Uncertain significance (Apr 22, 2022)
14-58252151-T-C		not specified	Uncertain significance (May 14, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSMA3	protein_coding	protein_coding	ENST00000216455	11	27182

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.985	0.0154	125629	0	3	125632	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.76	79	137	0.577	0.00000685	1675
Missense in Polyphen		8	38.595	0.20728		461
Synonymous	0.111	46	47.0	0.979	0.00000261	462
Loss of Function	3.61	1	17.1	0.0585	8.18e-7	223

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	0.0000463	0.0000462
European (Non-Finnish)	0.0000177	0.0000176
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 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Binds to the C-terminus of CDKN1A and thereby mediates its degradation. Negatively regulates the membrane trafficking of the cell-surface thromboxane A2 receptor (TBXA2R) isoform 2. {ECO:0000269|PubMed:11350925, ECO:0000269|PubMed:14550573, ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:17499743, ECO:0000269|PubMed:27176742}.
• Pathway: Proteasome - Homo sapiens (human);Proteasome Degradation;TLR NFkB;proteasome complex;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;Neddylation;Ub-specific processing proteases;JAK STAT pathway and regulation;Deubiquitination;TLR JNK;TNF;Wnt Canonical;Aurora B signaling;Wnt Mammals;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.400

Intolerance Scores

• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.46

Haploinsufficiency Scores

• pHI: 0.994
• hipred: Y
• hipred_score: 0.831
• ghis: 0.702

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.845

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Psma3

Gene ontology

• Biological process: proteasomal protein catabolic process;proteasomal ubiquitin-independent protein catabolic process;viral process;protein deubiquitination;proteasome-mediated ubiquitin-dependent protein catabolic process;post-translational protein modification;regulation of endopeptidase activity
• Cellular component: proteasome complex;nucleus;nucleoplasm;cytoplasm;cytosol;proteasome core complex;proteasome core complex, alpha-subunit complex;synapse;extracellular exosome
• Molecular function: endopeptidase activity;threonine-type endopeptidase activity;protein binding;ubiquitin protein ligase binding