PSMC3

Chr 11ARAD

proteasome 26S subunit, ATPase 3

Also known as: DCIDP, EBNDS, RPT5, TBP1

PSMC3 encodes an ATPase subunit of the 26S proteasome that unfolds ubiquitinated proteins for degradation, maintaining cellular protein homeostasis and participating in cell cycle progression, apoptosis, and DNA damage repair. Mutations cause Ebstein-Bezieau neurodevelopmental syndrome and a syndrome characterized by deafness, cataract, impaired intellectual development, and polyneuropathy, with both autosomal recessive and autosomal dominant inheritance patterns reported. The gene is highly constrained against loss-of-function variants (pLI 0.95, LOEUF 0.34), indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt
AR/ADLOEUF 0.342 OMIM phenotypes
Clinical SummaryPSMC3
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.34LOEUF
pLI 0.955
Z-score 3.86
OE 0.13 (0.060.34)
Highly constrained

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

Missense Constraint
3.87Z-score
OE missense 0.33 (0.270.39)
85 obs / 260.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.13 (0.060.34)
00.351.4
Missense OE0.33 (0.270.39)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 3 / 22.9Missense obs/exp: 85 / 260.7Syn Z: 0.62

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PSMC3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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