PSMB2

Chr 1

proteasome 20S subunit beta 2

Also known as: HC7-I

NCBI Gene: 5690 ENSG00000126067 UniProt: P49721 OMIM: 602175

The PSMB2 protein is a non-catalytic beta subunit of the 20S core proteasome complex that degrades intracellular proteins to maintain cellular protein homeostasis and generate MHC class I antigenic peptides. Mutations cause autosomal recessive proteasome-associated autoinflammatory syndrome, characterized by early-onset immunodeficiency, autoinflammation, and dermatitis. This gene is highly constrained against loss-of-function variants, indicating its essential cellular role.

OMIM ResearchSummary from RefSeq, UniProt

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. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

OMIM ResearchGenerating clinical summary…

LOEUF 0.39

Clinical Summary— PSMB2

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

24 VUS of 42 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.39LOEUF

pLI 0.914

Z-score 2.98

OE 0.08 (0.03–0.39)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.26Z-score

OE missense 0.68 (0.57–0.81)

82 obs / 120.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.08 (0.03–0.39)

0≤0.351.4

Missense OE?0.68 (0.57–0.81)

0≤0.61.4

Synonymous OE?0.69

0≤1.21.6

LoF obs/exp: 1 / 12.3Missense obs/exp: 82 / 120.9Syn Z: 1.62

ClinVar Variant Classifications

42 submitted variants in ClinVar

ClinVar

Classification Summary

VUS24

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	24	24
Likely Benign	0	0
Benign	0	0
Total	24	24

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

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9 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap PSMB2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →