SENP5
Chr 3SUMO specific peptidase 5
SENP5 encodes a protease that processes SUMO3 proteins to their mature form and removes SUMO2 and SUMO3 modifications from target proteins, functions that are essential for cell division and numerous biological processes. Mutations cause autosomal recessive developmental delay, seizures, and progressive microcephaly with onset in early childhood. This gene is highly constrained against loss-of-function variants, indicating that complete loss of SENP5 function is likely incompatible with normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
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
209 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 | 0 | 84 | 0 | 84 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 77 | 20 | 0 | 97 |
Likely Benign | 0 | 2 | 1 | 0 | 3 |
Benign | 0 | 2 | 1 | 1 | 4 |
Conflicting | — | 1 | |||
| Total | 0 | 81 | 109 | 1 | 192 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SENP5 · 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