SKI Gene - Proto-Oncogene, Transcriptional Regulator
SKI (SKI Proto-Oncogene) is a key regulator of TGF-β signaling, involved in cell proliferation, differentiation, and tumorigenesis.
Gene Information Card
| Symbol | SKI |
|---|---|
| Full Name | SKI proto-oncogene |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.33 |
| NCBI Gene ID | 6497 ncbi.nlm.nih.gov/gene/6497 |
| Ensembl ID | ENSG00000157933 |
| UniProt ID | P12755 |
| OMIM ID | 164780 |
| HGNC ID | 10896 |
| Aliases | SGS, SKV |
Description
The SKI gene encodes a nuclear proto-oncoprotein that acts as a transcriptional repressor of TGF-β signaling by interacting with SMAD proteins. It plays a critical role in cell growth, differentiation, and development. Overexpression or mutation of SKI is associated with various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Shprintzen-Goldberg syndrome | Heterozygous loss-of-function mutations in SKI disrupt TGF-β signaling, leading to craniosynostosis and aortic aneurysms. | OMIM #182212; ClinVar |
| Acute myeloid leukemia | SKI overexpression inhibits TGF-β-mediated growth suppression, contributing to leukemogenesis. | COSMIC; PMID: 10655551 |
| Colorectal cancer | SKI upregulation promotes epithelial-mesenchymal transition and metastasis. | COSMIC; PMID: 20010872 |
| Melanoma | SKI amplification or overexpression enhances cell proliferation and invasion. | COSMIC; PMID: 19351801 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.2 | Low |
| Heart | 5.1 | Low |
| Lung | 6.3 | Low |
| Liver | 4.7 | Low |
| Kidney | 7.9 | Low |
| Testis | 12.4 | Medium |
| Placenta | 15.6 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.3 | Embryonic kidney; moderate expression |
| HeLa | 22.1 | Cervical carcinoma; moderate expression |
| K562 | 9.8 | Leukemia; low expression |
| A549 | 14.5 | Lung carcinoma; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.272G>A (p.Arg91Gln) | Missense | Rare | Dominant-negative; associated with Shprintzen-Goldberg syndrome |
| c.346C>T (p.Arg116Trp) | Missense | Rare | Loss of SMAD binding; linked to aortic aneurysm |
| c.1123_1125del (p.Lys375del) | In-frame deletion | Rare | Impaired TGF-β repression; craniosynostosis |
| Amplification | Copy number gain | Frequent in melanoma | Increased SKI expression; promotes tumor growth |
Mutation functional classification
Loss of Function (LOF)
Heterozygous missense or deletion mutations in the SMAD-binding domain reduce SKI's ability to repress TGF-β signaling, leading to connective tissue disorders like Shprintzen-Goldberg syndrome.
Gain of Function (GOF)
Amplification or overexpression of SKI in cancers (e.g., melanoma, leukemia) enhances its oncogenic activity by constitutively repressing TGF-β tumor suppressor pathways.
Dominant Negative (DN)
Certain missense mutations (e.g., p.Arg91Gln) produce a protein that interferes with wild-type SKI function, disrupting TGF-β signaling and causing developmental defects.
View complete mutation data：
Gene Ontology (GO)
Pathways
• TGF-beta signaling pathway (KEGG: hsa04350)
• SMAD protein signal transduction (Reactome: R-HSA-2173793)
• Transcriptional regulation by RUNX1 (Reactome: R-HSA-8878171)
Protein Summary
The SKI protein (UniProt P12755) is a 728-amino acid nuclear proto-oncoprotein that functions as a transcriptional corepressor. It contains a conserved N-terminal domain that binds SMAD2, SMAD3, and SMAD4, thereby inhibiting TGF-β-induced transcription. SKI also interacts with histone deacetylases (HDACs) to repress target genes. Its dysregulation contributes to both developmental disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SKIDA1 Knockout HEK293 Cell Line | EDJ-KQ2152 | Human | 387640 | Details Get a Quote |
| SKIL Knockout HEK293 Cell Line | EDJ-KQ5755 | Human | 6498 | Details Get a Quote |
| SKIC2 Knockout HEK293 Cell Line | EDJ-KQ15270 | Human | 6499 | Details Get a Quote |
| SKIC3 Knockout HEK293 Cell Line | EDJ-KQ15271 | Human | 9652 | Details Get a Quote |
| SKIC8 Knockout HEK293 Cell Line | EDJ-KQ15272 | Human | 80349 | Details Get a Quote |
| SKIL Knockout A-549 Cell Line | EDJ-KQ29169 | Human | 6498 | Details Get a Quote |
| SKIL Knockout HCT 116 Cell Line | EDJ-KQ29170 | Human | 6498 | Details Get a Quote |
| SKIL Knockout HeLa Cell Line | EDJ-KQ29171 | Human | 6498 | Details Get a Quote |
| SKIC2 Knockout HCT 116 Cell Line | EDJ-KQ45964 | Human | 6499 | Details Get a Quote |
| SKIC2 Knockout HeLa Cell Line | EDJ-KQ45965 | Human | 6499 | Details Get a Quote |
| SKIC3 Knockout A-549 Cell Line | EDJ-KQ45966 | Human | 9652 | Details Get a Quote |
| SKIC3 Knockout HCT 116 Cell Line | EDJ-KQ45967 | Human | 9652 | Details Get a Quote |
| SKIC3 Knockout HeLa Cell Line | EDJ-KQ45968 | Human | 9652 | Details Get a Quote |
| SKIC8 Knockout A-549 Cell Line | EDJ-KQ45969 | Human | 80349 | Details Get a Quote |
| SKIC8 Knockout HeLa Cell Line | EDJ-KQ45971 | Human | 80349 | Details Get a Quote |
