PSMD11

Chr 17

proteasome 26S subunit, non-ATPase 11

Also known as: Rpn6, S9, p44.5

This protein is a non-ATPase subunit of the 26S proteasome that is required for proteasome assembly and participates in ATP-dependent degradation of ubiquitinated proteins to maintain cellular protein homeostasis. Loss-of-function mutations cause autosomal recessive neurodevelopmental disorder with developmental delay, intellectual disability, and seizures through impaired protein degradation and disrupted cellular processes including cell cycle progression and DNA damage repair. The gene is highly intolerant to loss-of-function variants (pLI = 1.0, LOEUF = 0.16), consistent with the severity of the associated phenotype.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
12
Pubs (1 yr)
14
P/LP submissions
7%
P/LP missense
0.16
LOEUF· LoF intol.
LOF
Mechanism· G2P
Clinical SummaryPSMD11
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.
📋
ClinVar Variants
14 unique Pathogenic / Likely Pathogenic· 44 VUS of 73 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.16LOEUF
pLI 1.000
Z-score 4.89
OE 0.03 (0.010.16)
Highly constrained

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

Missense Constraint
2.61Z-score
OE missense 0.52 (0.450.61)
123 obs / 235.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.03 (0.010.16)
00.351.4
Missense OE0.52 (0.450.61)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 1 / 29.8Missense obs/exp: 123 / 235.8Syn Z: -0.30

ClinVar Variant Classifications

73 submitted variants in ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic2
VUS44
Likely Benign1
12
Pathogenic
2
Likely Pathogenic
44
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
1
1
0
2
VUS
1
38
5
0
44
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total14018059

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

View in ClinVar →

Protein Context — Lollipop Plot

PSMD11 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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