PSMB9

proteasome 20S subunit beta 9, the group of Proteasome

Basic information

Region (hg38): 6:32844135-32859851

Previous symbols: [ "LMP2" ]

Links

ENSG00000240065 ∙ NCBI:5698 ∙ OMIM:177045 ∙ HGNC:9546 ∙ Uniprot:P28065 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Proteasome-associated autoinflammatory syndrome 3	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	26524591
Digenic inheritance has been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PSMB9 gene.

• not provided (6 variants)
• Inborn genetic diseases (4 variants)
• Proteasome-associated autoinflammatory syndrome 3 (2 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSMB9 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	1		2
missense		1	6		2	9
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	1	8	1	2

Highest pathogenic variant AF is 0.000197

Variants in PSMB9

This is a list of pathogenic ClinVar variants found in the PSMB9 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-32844305-CAG-C		Proteasome-associated autoinflammatory syndrome 1	Likely pathogenic (Mar 29, 2024)
6-32844751-C-T			Benign (May 15, 2021)
6-32844876-TTG-T			Benign (May 25, 2021)
6-32845024-G-A			Benign (May 14, 2021)
6-32845081-A-G			Benign (May 14, 2021)
6-32845139-T-C			Benign (Nov 12, 2018)
6-32845503-T-G			Likely benign (Dec 01, 2023)
6-32845587-G-A		not specified	Uncertain significance (Jun 16, 2023)
6-32845602-C-G		MHC class I deficiency	Uncertain significance (Sep 12, 2021)
6-32845607-A-G		MHC class I deficiency	Uncertain significance (Nov 29, 2022)
6-32845611-T-C		Inborn genetic diseases	Uncertain significance (May 11, 2022)
6-32845613-G-A		MHC class I deficiency • Inborn genetic diseases	Uncertain significance (Mar 25, 2022)
6-32845639-G-A		MHC class I deficiency	Likely benign (Apr 13, 2023)
6-32845644-G-T		MHC class I deficiency	Benign (Jan 16, 2024)
6-32845659-C-A		MHC class I deficiency • Inborn genetic diseases	Uncertain significance (Jan 19, 2022)
6-32845659-C-G		MHC class I deficiency	Uncertain significance (Dec 10, 2020)
6-32845671-C-T		MHC class I deficiency	Uncertain significance (May 20, 2022)
6-32845672-G-A		MHC class I deficiency	Likely benign (Aug 30, 2023)
6-32845677-C-A		MHC class I deficiency	Uncertain significance (Oct 16, 2019)
6-32845681-C-A		MHC class I deficiency	Likely benign (Aug 17, 2023)
6-32845682-A-C		MHC class I deficiency	Uncertain significance (Nov 22, 2021)
6-32845686-A-G		MHC class I deficiency	Uncertain significance (Oct 03, 2023)
6-32845687-G-T		MHC class I deficiency	Likely benign (Oct 13, 2023)
6-32845695-G-C		MHC class I deficiency	Uncertain significance (Oct 13, 2023)
6-32845705-C-T		MHC class I deficiency	Likely benign (Feb 24, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSMB9	protein_coding	protein_coding	ENST00000374859	6	15450

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00275	0.943	123314	0	29	123343	0.000118

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.934	103	133	0.772	0.00000762	1381
Missense in Polyphen		39	57.626	0.67678		631
Synonymous	1.89	35	52.4	0.668	0.00000323	465
Loss of Function	1.68	6	12.4	0.484	8.30e-7	120

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000174	0.000174
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000547	0.0000547
Finnish	0.00	0.00
European (Non-Finnish)	0.000154	0.000154
Middle Eastern	0.0000547	0.0000547
South Asian	0.000165	0.000165
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 PSMB6 by PSMB9 increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues. {ECO:0000269|PubMed:8163024}.
• Pathway: Proteasome - Homo sapiens (human);Proteasome Degradation;Type II interferon signaling (IFNG);TLR NFkB;antigen processing and presentation;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)

Intolerance Scores

• loftool: 0.733
• rvis_EVS: 0.64
• rvis_percentile_EVS: 83.78

Haploinsufficiency Scores

• pHI: 0.677
• hipred: Y
• hipred_score: 0.546
• ghis: 0.536

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.903

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Psmb9
• Phenotype: hematopoietic system phenotype; neoplasm; immune system phenotype

Gene ontology

• Biological process: immune system 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 cysteine-type endopeptidase activity
• 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