PSMB8

proteasome 20S subunit beta 8, the group of Proteasome

Basic information

Region (hg38): 6:32840716-32844679

Previous symbols: [ "LMP7" ]

Links

ENSG00000204264 ∙ NCBI:5696 ∙ OMIM:177046 ∙ HGNC:9545 ∙ Uniprot:P28062 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• proteasome-associated autoinflammatory syndrome 1 (Definitive), mode of inheritance: AR
• proteasome-associated autoinflammatory syndrome 1 (Moderate), mode of inheritance: AR
• proteosome-associated autoinflammatory syndrome (Supportive), mode of inheritance: AR
• proteasome-associated autoinflammatory syndrome 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Proteasome-associated autoinflammatory syndrome 1	AR/Digenic	Allergy/Immunology/Infectious; Cardiovascular	Individuals may have recurrent infections, and awareness may allow preventative measures as well as prompt and agressive treatment of infections; Individuals have been described with multiple manifestations, including lethal arrhythmias, and surveillance may allow early detection and management of cardiac sequelae	Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic	6499339; 4026345; 3618123; 8495043; 21129723; 20534754; 20159315; 21852578; 21881205; 21953331; 22441638; 26524591
Digenic inheritance has been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PSMB8 gene.

• Proteasome-associated autoinflammatory syndrome 1 (142 variants)
• Proteosome-associated autoinflammatory syndrome (30 variants)
• Autoinflammatory syndrome (30 variants)
• not provided (22 variants)
• not specified (8 variants)
• Inborn genetic diseases (5 variants)
• PROTEASOME-ASSOCIATED AUTOINFLAMMATORY SYNDROME 1, DIGENIC (1 variants)
• PSMB8-related condition (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSMB8 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			4	33	3	40
missense	1		93	3	1	98
nonsense	2	1				3
start loss						0
frameshift	2		1			3
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			3	2	1	6
non coding			6	10	9	25
Total	5	2	104	46	13

Highest pathogenic variant AF is 0.0000526

Variants in PSMB8

This is a list of pathogenic ClinVar variants found in the PSMB8 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-32840728-G-A		Proteasome-associated autoinflammatory syndrome 1	Uncertain significance (Jan 13, 2018)
6-32840781-C-T		Proteasome-associated autoinflammatory syndrome 1	Uncertain significance (Jan 13, 2018)
6-32840819-C-T		Proteasome-associated autoinflammatory syndrome 1	Benign (Jan 12, 2018)
6-32840843-G-A		Proteasome-associated autoinflammatory syndrome 1	Uncertain significance (Jan 13, 2018)
6-32840902-G-A		Proteasome-associated autoinflammatory syndrome 1	Uncertain significance (Jan 12, 2018)
6-32840935-C-A		Proteasome-associated autoinflammatory syndrome 1	Benign (Jan 13, 2018)
6-32840951-C-T		Proteasome-associated autoinflammatory syndrome 1 • Autoinflammatory syndrome	Conflicting classifications of pathogenicity (Apr 16, 2021)
6-32840953-C-G		Proteasome-associated autoinflammatory syndrome 1 • not specified • Autoinflammatory syndrome	Uncertain significance (Apr 01, 2020)
6-32840957-CATTATTG-C		Proteosome-associated autoinflammatory syndrome	Uncertain significance (May 15, 2022)
6-32840959-TTA-T		Proteosome-associated autoinflammatory syndrome	Uncertain significance (Jan 26, 2024)
6-32840975-C-T		Proteasome-associated autoinflammatory syndrome 1	Uncertain significance (Aug 16, 2022)
6-32840976-G-A		Proteosome-associated autoinflammatory syndrome	Uncertain significance (Jan 18, 2024)
6-32840978-T-C		Proteosome-associated autoinflammatory syndrome	Uncertain significance (May 19, 2022)
6-32840983-G-T		Proteosome-associated autoinflammatory syndrome	Uncertain significance (Aug 19, 2022)
6-32840986-C-T		not specified • Proteasome-associated autoinflammatory syndrome 1 • Autoinflammatory syndrome • Proteosome-associated autoinflammatory syndrome	Conflicting classifications of pathogenicity (Dec 07, 2023)
6-32840990-A-C		Proteosome-associated autoinflammatory syndrome	Uncertain significance (Jan 19, 2022)
6-32840992-G-C		Proteasome-associated autoinflammatory syndrome 1	Uncertain significance (Aug 09, 2022)
6-32841005-G-GTACTTTC		Proteosome-associated autoinflammatory syndrome	Uncertain significance (Apr 01, 2022)
6-32841028-A-G		Proteosome-associated autoinflammatory syndrome	Likely benign (Dec 13, 2021)
6-32841031-T-G		Proteosome-associated autoinflammatory syndrome	Uncertain significance (Jul 15, 2022)
6-32841034-C-T		Autoinflammatory syndrome • Proteosome-associated autoinflammatory syndrome	Conflicting classifications of pathogenicity (Aug 30, 2020)
6-32841035-T-G		Proteosome-associated autoinflammatory syndrome	Uncertain significance (Jul 06, 2022)
6-32841052-G-A		Proteosome-associated autoinflammatory syndrome	Uncertain significance (Dec 22, 2021)
6-32841299-G-A			Benign (Nov 12, 2018)
6-32841446-C-A		not specified	Benign (Nov 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSMB8	protein_coding	protein_coding	ENST00000374882	6	3987

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0218	0.964	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.651	138	161	0.856	0.00000977	1772
Missense in Polyphen		49	58.802	0.83331		654
Synonymous	-0.972	71	61.3	1.16	0.00000341	560
Loss of Function	2.14	5	13.5	0.371	6.78e-7	154

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000154	0.000149
Ashkenazi Jewish	0.00109	0.00109
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000905	0.0000879
Middle Eastern	0.000109	0.000109
South Asian	0.0000659	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB5 by PSMB8 increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues. Acts as a major component of interferon gamma-induced sensitivity. Plays a key role in apoptosis via the degradation of the apoptotic inhibitor MCL1. May be involved in the inflammatory response pathway. In cancer cells, substitution of isoform 1 (E2) by isoform 2 (E1) results in immunoproteasome deficiency. Required for the differentiation of preadipocytes into adipocytes. {ECO:0000269|PubMed:16423992, ECO:0000269|PubMed:19443843, ECO:0000269|PubMed:21881205, ECO:0000269|PubMed:8163024}.
• Disease: DISEASE: Proteasome-associated autoinflammatory syndrome 1 (PRAAS1) [MIM:256040]: An autosomal recessive autoinflammatory disorder characterized by early childhood onset of recurrent fever, joint stiffness and severe contractures of the hands and feet, and erythematous skin lesions with subsequent development of lipodystrophy and laboratory evidence of immune dysregulation. Accompanying features may include muscle weakness and atrophy, hepatosplenomegaly, and microcytic anemia. {ECO:0000269|PubMed:21129723, ECO:0000269|PubMed:21852578, ECO:0000269|PubMed:21881205, ECO:0000269|PubMed:21953331, ECO:0000269|PubMed:26524591, ECO:0000269|PubMed:26567544}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Proteasome - Homo sapiens (human);Proteasome Degradation;The human immune response to tuberculosis;TLR NFkB;antigen processing and presentation;Cytokine Signaling in Immune system;B cell receptor signaling;Post-translational protein modification;Metabolism of proteins;DroToll-like;Notch;Hedgehog;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;TLR JNK;Interferon alpha/beta signaling;TNF;Wnt Canonical;Interferon Signaling;Wnt Mammals;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Intolerance Scores

• loftool: 0.856
• rvis_EVS: 0.04
• rvis_percentile_EVS: 57.15

Haploinsufficiency Scores

• pHI: 0.409
• hipred: N
• hipred_score: 0.271
• ghis: 0.525

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Psmb8
• Phenotype: immune system phenotype; neoplasm; hematopoietic system phenotype

Gene ontology

• Biological process: proteasomal protein catabolic process;proteasomal ubiquitin-independent protein catabolic process;viral process;protein deubiquitination;antigen processing and presentation;proteasome-mediated ubiquitin-dependent protein catabolic process;post-translational protein modification;fat cell differentiation;regulation of endopeptidase activity;type I interferon signaling pathway
• Cellular component: proteasome complex;nucleus;nucleoplasm;cytoplasm;cytosol;proteasome core complex;proteasome core complex, beta-subunit complex;extracellular exosome;spermatoproteasome complex
• Molecular function: endopeptidase activity;threonine-type endopeptidase activity;protein binding