PSMC2

Chr 7

proteasome 26S subunit, ATPase 2

Also known as: MSS1, Nbla10058, RPT1, S7

The protein is 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 autosomal recessive neurodevelopmental disorder with microcephaly, seizures, and brain abnormalities. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.12), indicating that even heterozygous loss is typically incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.12
Clinical SummaryPSMC2
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.12LOEUF
pLI 1.000
Z-score 4.64
OE 0.00 (0.000.12)
Highly constrained

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

Missense Constraint
3.62Z-score
OE missense 0.36 (0.300.43)
90 obs / 251.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.000.12)
00.351.4
Missense OE0.36 (0.300.43)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 0 / 25.1Missense obs/exp: 90 / 251.6Syn Z: 0.48
DN
0.4488th %ile
GOF
0.3391th %ile
LOF
0.75top 10%

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PSMC2 · 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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