PSMC1
Chr 14ARproteasome 26S subunit, ATPase 1
Also known as: NEDGTH, P26S4, RPT2, S4, p56
PSMC1 encodes an ATPase subunit of the 26S proteasome, a multiprotein complex that degrades ubiquitinated proteins in an ATP-dependent manner to maintain cellular protein homeostasis. Mutations cause Birk-Aharoni syndrome, though the phenotypic spectrum remains incompletely defined. The condition follows autosomal recessive inheritance.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
46 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 1 | 18 | 0 | 19 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 9 | 5 | 0 | 14 |
Likely Benign | 0 | 0 | 0 | 2 | 2 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 0 | 10 | 24 | 3 | 37 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PSMC1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools