SKIL
protein-codingSKI like proto-oncogene, the group of SKI transcriptional corepressors
Gene summary
The protein encoded by this gene is a component of the SMAD pathway, which regulates cell growth and differentiation through transforming growth factor-beta (TGFB). In the absence of ligand, the encoded protein binds to the promoter region of TGFB-responsive genes and recruits a nuclear repressor complex. TGFB signaling causes SMAD3 to enter the nucleus and degrade this protein, allowing these genes to be activated. Four transcript variants encoding three different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~39.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SKIL variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005414.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 1 | 4 | |||
| missense | 90 | 5 | 1 | 96 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 94 | 5 | 2 | 101 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005405.2 | 6 | MANE Select | |
| Ensembl | ENSP00000259119.4 | 6 | MANE Select | |
| RefSeq | NP_001138569.1 | 6 | Standard | |
| RefSeq | NP_001138570.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
- TGF-Ncore
- Ectoderm Differentiation
- Lung fibrosis
- TGF-beta Signaling Pathway
Biological Process
- negative regulation of transcription by RNA polymerase II
- blastocyst formation
- lymphocyte homeostasis
- cell cycle arrest
- transforming growth factor beta receptor signaling pathway
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- chromatin binding
- protein binding
Cellular Component
- acrosomal vesicle
- nucleoplasm
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000458537
- Coding exons
- 6
- Length
- 39158
- Individuals with no LoFs
- 125733
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 14
- Defined
- 125747
- p
- 0.0000557
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.928 | 296 | 344 | 0.859 | 0.0000165 | 4479 |
| Missense (PolyPhen) | 86 | 131.45 | 0.65426 | 1711 | ||
| Synonymous | -0.967 | 142 | 128 | 1.11 | 0.00000636 | 1267 |
| Loss of Function | 4.44 | 4 | 30.4 | 0.132 | 0.00000155 | 416 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.000072 | 0.000070 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May have regulatory role in cell division or differentiation in response to extracellular signals.;
Intolerance Scores
- LoFtool
- 0.0258
- RVIS EVS
- -0.33
- RVIS percentile EVS
- 30.7
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |