PSMB4

proteasome 20S subunit beta 4, the group of Proteasome

Basic information

Region (hg38): 1:151399560-151401937

Links

ENSG00000159377 ∙ NCBI:5692 ∙ OMIM:602177 ∙ HGNC:9541 ∙ Uniprot:P28070 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• proteasome-associated autoinflammatory syndrome 3 (Limited), mode of inheritance: AR
• proteasome-associated autoinflammatory syndrome 3 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Proteasome-associated autoinflammatory syndrome 3	AR/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; Dermatologic; 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 PSMB4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSMB4 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				27	3	30
missense			96	3	1	100
nonsense			1			1
start loss			2	1		3
frameshift			4			4
inframe indel			3			3
splice donor/acceptor (+/-2bp)						0
splice region			3	13		16
non coding			2	34	7	43
Total	0	0	108	65	11

Variants in PSMB4

This is a list of pathogenic ClinVar variants found in the PSMB4 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-151399579-G-A		Proteasome-associated autoinflammatory syndrome 3 • PSMB4-related disorder	Uncertain significance (Jan 31, 2024)
1-151399588-A-C			Uncertain significance (Apr 05, 2021)
1-151399588-A-G			Uncertain significance (May 08, 2022)
1-151399589-T-C			Likely benign (Jun 05, 2023)
1-151399597-T-C		not specified	Conflicting classifications of pathogenicity (May 27, 2023)
1-151399600-T-C			Likely benign (Jul 12, 2022)
1-151399601-T-G		not specified	Uncertain significance (Jan 30, 2024)
1-151399605-G-A		PSMB4-related disorder	Benign (Jan 25, 2024)
1-151399609-C-T			Uncertain significance (Apr 15, 2022)
1-151399610-G-C			Uncertain significance (Dec 09, 2023)
1-151399613-C-T		not specified	Uncertain significance (May 04, 2023)
1-151399615-G-A			Uncertain significance (Oct 13, 2023)
1-151399616-G-T			Uncertain significance (Dec 10, 2023)
1-151399625-C-T			Uncertain significance (Dec 01, 2020)
1-151399625-C-CG		Proteasome-associated autoinflammatory syndrome 3	Uncertain significance (May 05, 2022)
1-151399626-G-A			Likely benign (May 31, 2023)
1-151399626-G-T			Likely benign (Dec 03, 2022)
1-151399627-G-A			Uncertain significance (Nov 01, 2022)
1-151399630-G-A		PSMB4-related disorder	Uncertain significance (Apr 11, 2024)
1-151399630-G-C			Uncertain significance (Oct 14, 2022)
1-151399633-C-T			Uncertain significance (Jan 12, 2024)
1-151399636-G-T		not specified	Uncertain significance (Jan 23, 2024)
1-151399637-C-T			Uncertain significance (Mar 01, 2023)
1-151399654-C-A			Uncertain significance (Mar 20, 2022)
1-151399654-C-T			Uncertain significance (May 18, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSMB4	protein_coding	protein_coding	ENST00000290541	7	2411

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00264	0.985	125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.467	142	159	0.896	0.00000917	1697
Missense in Polyphen		25	52.479	0.47638		546
Synonymous	0.123	59	60.2	0.980	0.00000349	546
Loss of Function	2.18	7	16.6	0.422	9.69e-7	167

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000177	0.000177
Ashkenazi Jewish	0.0000997	0.0000992
East Asian	0.0000545	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000704	0.0000703
Middle Eastern	0.0000545	0.0000544
South Asian	0.00	0.00
Other	0.000163	0.000163

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). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1. {ECO:0000269|PubMed:12097147, ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}.
• 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;Wnt Mammals;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.296

Intolerance Scores

• loftool: 0.749
• rvis_EVS: -0.05
• rvis_percentile_EVS: 49.76

Haploinsufficiency Scores

• pHI: 0.866
• hipred: Y
• hipred_score: 0.711
• ghis: 0.638

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.756

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Psmb4

Gene ontology

• Biological process: negative regulation of inflammatory response to antigenic stimulus;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
• Cellular component: proteasome complex;nucleus;nucleoplasm;cytoplasm;cytosol;proteasome core complex;proteasome core complex, beta-subunit complex;extracellular exosome
• Molecular function: lipopolysaccharide binding;endopeptidase activity;threonine-type endopeptidase activity;protein binding