PSMB1

Chr 6AR

proteasome 20S subunit beta 1

Also known as: HC5, NEDMHAL, PMSB1, PSC5

NCBI Gene: 5689 ENSG00000008018 UniProt: P20618 OMIM: 602017

PSMB1 encodes a non-catalytic beta subunit of the 20S proteasome core complex, which degrades intracellular proteins through both ubiquitin-dependent and ubiquitin-independent pathways to maintain cellular protein homeostasis. Mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, hypotonia, and absent language. The gene is highly constrained against loss-of-function variants (pLI 0.97, LOEUF 0.28), indicating that functional copies are critical for normal development.

OMIM ResearchSummary from RefSeq, OMIM, 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. This gene is tightly linked to the TBP (TATA-binding protein) gene in human and in mouse, and is transcribed in the opposite orientation in both species. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

ARLOEUF 0.281 OMIM phenotype

Clinical Summary— PSMB1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 23 VUS of 30 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.28LOEUF

pLI 0.970

Z-score 3.05

OE 0.00 (0.00–0.28)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.87Z-score

OE missense 0.79 (0.68–0.93)

109 obs / 137.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.28)

0≤0.351.4

Missense OE?0.79 (0.68–0.93)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 0 / 10.8Missense obs/exp: 109 / 137.9Syn Z: -0.37

ClinVar Variant Classifications

30 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS23

Likely Benign2

Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	1	1
Likely Pathogenic	0	0
VUS	23	23
Likely Benign	2	2
Benign	0	0
Total	26	26

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

View in ClinVar →

86 pathogenic / likely-pathogenic (of 104) ClinVar copy-number / structural variants overlap PSMB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →