PSMD1

Chr 2

proteasome 26S subunit, non-ATPase 1

Also known as: P112, Rpn2, S1

NCBI Gene: 5707ENSG00000173692UniProt: Q99460

The PSMD1 protein is the largest non-ATPase subunit of the 26S proteasome's 19S regulator lid, responsible for substrate recognition and binding in the ATP-dependent degradation of ubiquitinated proteins essential for cellular protein homeostasis. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, developmental delay, and seizures. This gene is highly constrained against loss-of-function variants, indicating that even single functional copies may be insufficient for normal development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
9
Pubs (1 yr)
28
P/LP submissions
0%
P/LP missense
0.12
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— PSMD1
⚡
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
28 unique Pathogenic / Likely Pathogenic· 116 VUS of 186 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.12LOEUF
pLI 1.000
Z-score 6.50
OE 0.04 (0.01–0.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.70Z-score
OE missense 0.54 (0.48–0.59)
271 obs / 504.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.04 (0.01–0.12)
0≤0.351.4
Missense OE0.54 (0.48–0.59)
0≤0.61.4
Synonymous OE0.94
0≤1.21.6
LoF obs/exp: 2 / 53.2Missense obs/exp: 271 / 504.7Syn Z: 0.59
DN
0.4091th %ile
GOF
0.3788th %ile
LOF
0.66top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.12

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

186 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
VUS116
Likely Benign4
Benign9
28
Pathogenic
116
VUS
4
Likely Benign
9
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
28
0
28
Likely Pathogenic
0
0
0
0
0
VUS
0
112
4
0
116
Likely Benign
0
2
1
1
4
Benign
0
4
2
3
9
Total0118354157

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

View in ClinVar →

Protein Context — Lollipop Plot

PSMD1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients