PSMB10

proteasome 20S subunit beta 10, the group of Proteasome

Basic information

Region (hg38): 16:67934505-67936864

Previous symbols: [ "MECL1" ]

Links

ENSG00000205220 ∙ NCBI:5699 ∙ OMIM:176847 ∙ HGNC:9538 ∙ Uniprot:P40306 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• proteasome-associated autoinflammatory syndrome 5 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 121 with autoinflammation; Proteasome-associated autoinflammatory syndrome 5	AD/AR	Allergy/Immunology/Infectious	Immunodeficiency 121 with autoinflammation involves severe immunodeficiency, and awareness may allow early and aggressive treatment of infections as well as preventative measures; HSCT has been described, but complications have been reported in multiple individuals; Proteasome-associated autoinflammatory syndrome 5 involves autoinflammatory manifestations, and medical management (eg, with steroids and methotrexate) has been described as beneficial	Allergy/Immunology/Infectious; Dermatologic	31783057; 38503300

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PSMB10 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSMB10 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		2
missense			10	3		13
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	11	5	0

Variants in PSMB10

This is a list of pathogenic ClinVar variants found in the PSMB10 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-67934646-C-T		Proteasome-associated autoinflammatory syndrome 5 • not specified	Uncertain significance (Aug 08, 2023)
16-67934663-C-A		not specified	Uncertain significance (May 21, 2024)
16-67934664-G-A		not specified	Uncertain significance (Mar 31, 2023)
16-67934671-C-T		not specified	Likely benign (Oct 13, 2023)
16-67934796-C-G		Proteasome-associated autoinflammatory syndrome 5	Pathogenic (Jun 11, 2024)
16-67934804-C-T		not specified	Uncertain significance (Dec 07, 2023)
16-67934847-A-G			Likely benign (Sep 01, 2022)
16-67934864-A-T		not specified	Uncertain significance (Apr 17, 2023)
16-67934878-C-T		Proteasome-associated autoinflammatory syndrome 5	Uncertain significance (Jun 01, 2022)
16-67934906-C-G		Immunodeficiency 121 with autoinflammation	Pathogenic (Jun 11, 2024)
16-67934906-C-T		Immunodeficiency 121 with autoinflammation	Pathogenic (Jun 11, 2024)
16-67935478-C-T		Proteasome-associated autoinflammatory syndrome 5	Pathogenic (Jun 11, 2024)
16-67935657-C-T		not specified	Uncertain significance (Feb 17, 2022)
16-67935680-C-T		not specified	Uncertain significance (Dec 28, 2022)
16-67935979-G-A		not specified	Likely benign (Nov 22, 2023)
16-67935985-T-C		not specified	Likely benign (May 23, 2023)
16-67936095-C-T		not specified	Uncertain significance (Mar 01, 2024)
16-67936098-C-CA		Proteasome-associated autoinflammatory syndrome 5	Pathogenic (Jun 11, 2024)
16-67936239-ATCT-A		PSMB10-related disorder	Uncertain significance (Mar 14, 2023)
16-67936291-C-G		Immunodeficiency 121 with autoinflammation	Pathogenic (Jun 11, 2024)
16-67936309-C-G		not specified	Uncertain significance (Mar 31, 2022)
16-67936697-T-G			Likely benign (Jan 01, 2023)
16-67936705-C-A		not specified	Uncertain significance (Jan 30, 2024)
16-67936707-CGAA-C		Proteasome-associated autoinflammatory syndrome 5	Pathogenic (Jun 11, 2024)
16-67936709-A-G		Proteasome-associated autoinflammatory syndrome 5	Pathogenic (Jun 11, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSMB10	protein_coding	protein_coding	ENST00000358514	8	2586

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000177	0.445	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.694	139	164	0.848	0.00000795	1705
Missense in Polyphen		24	47.872	0.50133		494
Synonymous	0.0879	74	75.0	0.987	0.00000395	610
Loss of Function	0.630	10	12.4	0.807	5.30e-7	144

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00119	0.00116
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000927	0.0000924
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.000109	0.000109
South Asian	0.0000983	0.0000980
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.
• Pathway: Proteasome - Homo sapiens (human);Proteasome Degradation;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;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: 0.191

Intolerance Scores

• loftool: 0.693
• rvis_EVS: -0.41
• rvis_percentile_EVS: 26.23

Haploinsufficiency Scores

• pHI: 0.678
• hipred: Y
• hipred_score: 0.595
• ghis: 0.585

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.525

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Psmb10
• Phenotype: homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); immune system 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); hematopoietic system phenotype

Gene ontology

• Biological process: cell morphogenesis;humoral immune response;proteasomal protein catabolic process;proteasomal ubiquitin-independent protein catabolic process;viral process;protein deubiquitination;T cell proliferation;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;spermatoproteasome complex
• Molecular function: endopeptidase activity;threonine-type endopeptidase activity;protein binding