PSMD6

Chr 3

proteasome 26S subunit, non-ATPase 6

Also known as: Rpn7, S10, SGA-113M, p42A, p44S10

NCBI Gene: 9861 ENSG00000163636 UniProt: Q15008

The encoded protein is a component of the 26S proteasome, a multiprotein complex that degrades ubiquitinated proteins in an ATP-dependent manner to maintain cellular protein homeostasis and participate in cell cycle progression, apoptosis, and DNA damage repair. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy or early childhood. This gene is highly constrained against loss-of-function mutations in the general population.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the protease subunit S10 family. The encoded protein is a subunit of the 26S proteasome which colocalizes with DNA damage foci and is involved in the ATP-dependent degradation of ubiquinated proteins. Alternative splicing results in multiple transcript variants [provided by RefSeq, Nov 2012]

ResearchGenerating clinical summary…

LOEUF 0.23

Clinical Summary— PSMD6

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

45 VUS of 61 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.23LOEUF

pLI 0.995

Z-score 3.96

OE 0.05 (0.02–0.23)

Highly constrained

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

Missense Constraint?

1.26Z-score

OE missense 0.76 (0.67–0.86)

163 obs / 214.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.05 (0.02–0.23)

0≤0.351.4

Missense OE?0.76 (0.67–0.86)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 1 / 20.2Missense obs/exp: 163 / 214.8Syn Z: -1.08

ClinVar Variant Classifications

61 submitted variants in ClinVar

ClinVar

Classification Summary

VUS45

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	2	43	45
Likely Benign	0	0	0
Benign	0	0	0
Total	2	43	45

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 12) ClinVar copy-number / structural variants overlap PSMD6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →