PSMB10
protein-codingproteasome 20S subunit beta 10, the group of Proteasome
Gene summary
The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. Proteolytic processing is required to generate a mature subunit. Expression of this gene is induced by gamma interferon, and this gene product replaces catalytic subunit 2 (proteasome beta 7 subunit) in the immunoproteasome. [provided by RefSeq, Jul 2008]
- MECL1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0030924
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0030924
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0030924
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0971001
Submitter: ClinGen
Heterozygous germline variants in PSMB10 were first reported in relationship to PSMB10-related severe combined immunodeficiency in 2022 (PMID: 36250618). Reports describe patients that present early in life with T-/B-/natural killer (NK) cell+ severe combined immunodeficiency with some patients also developing Omenn syndrome (PMID:38503300). All cases are reported to arise from heterozygous, likely de novo missense mutations (two mutations across seven cases) that are predicted to result in a dominant-negative impact on the function of the PSMB10 encoded protein, β2i. β2i is a component of the immunoproteasome and thymoproteasome, which are unique proteasomes with altered formation kinetics and antigen processing capabilities compared to the standard proteasome. These missense mutations are hypothesized to alter steric interactions with other components of the proteasome, destabilizing proteasome formation and structure. Studies have shown that these PSMB10 variants likely have an intrinsic impact on the function and survival of thymic epithelial cells (TEC), thymocytes and peripheral lymphocytes (PMID:29654304, 39734035). Of note, bone marrow transplant has not been curative for most patients, supporting the findings that PSMB10 variants impact both the hematopoietic and thymic components of the immune system. A mouse model harboring a heterozygous missense mutation in Psmb10 partially phenocopies the human disease, exhibiting T and B cell lymphopenia and poor antigen-specific T cell function (PMID:29654304). In summary, there is currently limited evidence to support this gene-disease relationship. This classification was approved by the ClinGen SCID-CID Working Group on 4/17/2025 (SOP Version 11).
Inheritance Pattern: AD
Disease ID:MONDO:0971001
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0971001
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Dermatologic
Intervention: Allergy/Immunology/Infectious
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PSMB10 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002801.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | 6 | ||||
| missense | 5 | 37 | 4 | 46 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 1 | 2 | 4 | 7 | ||
| Total | 7 | 2 | 42 | 10 | 0 | 61 |
Highest pathogenic variant AF is 0.00037765809
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002792.1 | 8 | MANE Select | |
| Ensembl | ENSP00000351314.4 | 8 | MANE Select | |
| Ensembl | ENSP00000463811.1 | 5 | Standard | |
| Ensembl | ENSP00000534517.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Proteasome - Homo sapiens (human)
- Proteasome Degradation
- TLR NFkB
- B cell receptor signaling
- Post-translational protein modification
Biological Process
- cell morphogenesis
- humoral immune response
- proteasomal protein catabolic process
- proteasomal ubiquitin-independent protein catabolic process
- viral process
Molecular Function
- endopeptidase activity
- threonine-type endopeptidase activity
- protein binding
Cellular Component
- proteasome complex
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000358514
- Coding exons
- 8
- Length
- 2586
- Individuals with no LoFs
- 125704
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 44
- Defined
- 125748
- p
- 0.000175
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.694 | 139 | 164 | 0.848 | 0.00000795 | 1705 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0011 | 0.0010 | notable |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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.;
Recessive Scores
- pRec
- 0.191
Intolerance Scores
- LoFtool
- 0.693
- RVIS EVS
- -0.41
- RVIS percentile EVS
- 26.23
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.525
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |