SKI
Chr 1ADSKI proto-oncogene
Also known as: SGS, SKV
The SKI protein functions as a repressor of TGF-beta signaling and plays a role in neural tube development and muscle differentiation. Mutations cause Shprintzen-Goldberg syndrome, a connective tissue disorder with craniosynostosis, arachnodactyly, and intellectual disability. This gene follows autosomal dominant inheritance and is highly constrained against loss-of-function mutations (pLI 0.999).
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
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
500 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 | 5 | 0 | 6 |
Likely Pathogenic | 1 | 2 | 0 | 0 | 3 |
VUS | 15 | 241 | 15 | 2 | 273 |
Likely Benign | 0 | 14 | 30 | 159 | 203 |
Benign | 0 | 0 | 3 | 1 | 4 |
Conflicting | — | 7 | |||
| Total | 16 | 258 | 53 | 162 | 496 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SKI · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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