SKI

Chr 1AD

SKI proto-oncogene

Also known as: SGS, SKV

NCBI Gene: 6497ENSG00000157933UniProt: P12755

This gene encodes the nuclear protooncogene protein homolog of avian sarcoma viral (v-ski) oncogene. It functions as a repressor of TGF-beta signaling, and may play a role in neural tube development and muscle differentiation. [provided by RefSeq, Oct 2009]

Primary Disease Associations & Inheritance

Shprintzen-Goldberg syndromeMIM #182212
AD
0
Active trials
13
Pathogenic / LP
496
ClinVar variants
217
Pubs (1 yr)
1.5
Missense Z
0.19
LOEUF· LoF intolerant
Clinical Summary— SKI
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Gene-Disease Validity (ClinGen)
Shprintzen-Goldberg syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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.
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ClinVar Variants
13 Pathogenic / Likely Pathogenic· 278 VUS of 496 total submissions
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GeneReview available — SKI
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.19LOEUF
pLI 0.999
Z-score 4.40
OE 0.04 (0.01–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.51Z-score
OE missense 0.80 (0.73–0.87)
349 obs / 438.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.04 (0.01–0.19)
0≤0.351.4
Missense OE0.80 (0.73–0.87)
0≤0.61.4
Synonymous OE1.43
0≤1.21.6
LoF obs/exp: 1 / 24.5Missense obs/exp: 349 / 438.2Syn Z: -4.87
LOF
DN
0.3097th %ile
GOF
0.3293th %ile
LOF
0.82top 5%

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

LOFprediction above median · LOEUF 0.19

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

496 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic3
VUS278
Likely Benign195
Benign5
Conflicting5
10
Pathogenic
3
Likely Pathogenic
278
VUS
195
Likely Benign
5
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
7
0
10
Likely Pathogenic
1
2
0
0
3
VUS
12
236
27
3
278
Likely Benign
0
13
31
151
195
Benign
0
0
4
1
5
Conflicting
—5
Total1325469155496

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

View in ClinVar →

SKI · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SKI-related Shprintzen-Goldberg craniosynostosis syndrome

definitive
ADUndeterminedAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
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
Loeys-Dietz Syndrome.
Velchev JD et al.·Adv Exp Med Biol
2021
Synthetic lethality of mRNA quality control complexes in cancer.
Prindle V et al.·Nature
2025
SKI complex loss renders 9p21.3-deleted or MSI-H cancers dependent on PELO.
Borck PC et al.·Nature
2025
Alpine Skiing Injuries.
Davey A et al.·Sports Health
2019Review
Ski: Double roles in cancers.
Liao HY et al.·Clin Biochem
2021Review
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Five-year interim analysis of J-SKI: an observational study of TKI discontinuation in patients with CML in Japan.
Takahashi N et al.·Int J Hematol
2026Cohort
International Ski and Snowboard Federation (FIS) consensus statement on return-to-performance in competitive alpine and freestyle skiers and snowboarders.
Spörri J et al.·BMJ Open Sport Exerc Med
2026Open Access
The influence of suit size on performance in ski jumping. Part II: field measurements.
Elfmark O et al.·Front Sports Act Living
2026Open Access
Physical and Ski Technical Factors Associated with ACL Injury Susceptibility in Elite and Recreational Alpine Skiers.
Kékesi M et al.·J Funct Morphol Kinesiol
2026Open Access
Perceptual consensus on cross-country ski-snow performance: a questionnaire study of experts and non-experts.
Kalén A et al.·Front Sports Act Living
2026Open Access
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