PSMD5

Chr 9

proteasome 26S subunit, non-ATPase 5

Also known as: S5B

This protein functions as a chaperone during assembly of the 26S proteasome, specifically facilitating formation of the base subcomplex of the 19S regulatory component that is essential for ATP/ubiquitin-dependent protein degradation. Mutations in PSMD5 cause autosomal recessive neurodevelopmental disorder with microcephaly, seizures, and brain atrophy through impaired proteasome assembly leading to defective cellular protein homeostasis. The pathogenic mechanism involves disruption of the critical chaperone function required for proper 26S proteasome formation.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.04
Clinical SummaryPSMD5
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 69 VUS of 108 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.04LOEUF
pLI 0.000
Z-score 1.43
OE 0.67 (0.451.04)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.29Z-score
OE missense 0.95 (0.861.05)
255 obs / 268.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.67 (0.451.04)
00.351.4
Missense OE0.95 (0.861.05)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 15 / 22.3Missense obs/exp: 255 / 268.2Syn Z: 0.56

ClinVar Variant Classifications

108 submitted variants in ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic1
VUS69
Likely Benign2
21
Pathogenic
1
Likely Pathogenic
69
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
1
0
1
VUS
0
68
1
0
69
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total07023093

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

View in ClinVar →

Protein Context — Lollipop Plot

PSMD5 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC