SKI
SKI proto-oncogene, the group of SKI transcriptional corepressors
Basic information
Region (hg38): 1:2227388-2310213
Links
Phenotypes
GenCC
Source:
- Shprintzen-Goldberg syndrome (Definitive), mode of inheritance: AD
- Shprintzen-Goldberg syndrome (Strong), mode of inheritance: AD
- Shprintzen-Goldberg syndrome (Strong), mode of inheritance: AD
- Shprintzen-Goldberg syndrome (Strong), mode of inheritance: AD
- Shprintzen-Goldberg syndrome (Definitive), mode of inheritance: AD
- Shprintzen-Goldberg syndrome (Supportive), mode of inheritance: AD
- Shprintzen-Goldberg syndrome (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Shprintzen-Goldberg craniosynostosis syndrome | AD | Cardiovascular | Individuals have been described with a number of cardiovascular anomalies, including aortic root dilatation, and spontaneous rupture of arterial aneurysms, and surveillance (eg, including echocardiogram) may allow early management, decreasing morbidity and mortality | Cardiovascular; Craniofacial; Musculoskeletal; Neurologic | 23023332 |
ClinVar
This is a list of variants' phenotypes submitted to
- Shprintzen-Goldberg_syndrome (812 variants)
- Familial_thoracic_aortic_aneurysm_and_aortic_dissection (673 variants)
- not_provided (317 variants)
- not_specified (95 variants)
- SKI-related_disorder (36 variants)
- Intellectual_disability (5 variants)
- Inborn_genetic_diseases (4 variants)
- Neurodevelopmental_disorder (3 variants)
- Isolated_thoracic_aortic_aneurysm (3 variants)
- Disproportionate_tall_stature (2 variants)
- See_cases (2 variants)
- Craniosynostosis_syndrome (1 variants)
- Autism_spectrum_disorder (1 variants)
- Arterial_dissection (1 variants)
- Cardiovascular_phenotype (1 variants)
- Neurodevelopmental_abnormality (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SKI gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003036.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 474 | 484 | ||||
| missense | 12 | 17 | 531 | 85 | 647 | |
| nonsense | 7 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 17 | 20 | ||||
| splice donor/acceptor (+/-2bp) | 5 | |||||
| Total | 13 | 19 | 566 | 559 | 7 |
Highest pathogenic variant AF is 8.04018e-7
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SKI | protein_coding | protein_coding | ENST00000378536 | 7 | 81425 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.000985 | 125412 | 0 | 3 | 125415 | 0.0000120 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.51 | 349 | 438 | 0.796 | 0.0000288 | 4563 |
| Missense in Polyphen | 93 | 185.76 | 0.50065 | 1946 | ||
| Synonymous | -4.87 | 300 | 210 | 1.43 | 0.0000147 | 1536 |
| Loss of Function | 4.40 | 1 | 24.5 | 0.0409 | 0.00000123 | 293 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.000101 | 0.0000996 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000177 | 0.0000177 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: May play a role in terminal differentiation of skeletal muscle cells but not in the determination of cells to the myogenic lineage. Functions as a repressor of TGF-beta signaling. {ECO:0000269|PubMed:19049980}.;
- Disease
- DISEASE: Shprintzen-Goldberg craniosynostosis syndrome (SGS) [MIM:182212]: A very rare syndrome characterized by a marfanoid habitus, craniosynostosis, characteristic dysmorphic facial features, skeletal and cardiovascular abnormalities, mental retardation, developmental delay and learning disabilities. {ECO:0000269|PubMed:23023332, ECO:0000269|PubMed:23103230, ECO:0000269|PubMed:24357594, ECO:0000269|PubMed:24736733}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- TGF-Ncore;Olfactory bulb development and olfactory learning;TGF-beta Signaling Pathway;TGF-beta Receptor Signaling;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Notch;Downregulation of SMAD2/3:SMAD4 transcriptional activity;TGF-beta super family signaling pathway canonical;TGF_beta_Receptor;Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer;BMP receptor signaling;C-MYB transcription factor network;Signaling by TGF-beta Receptor Complex;Signaling by BMP;Signaling by TGF-beta family members;Regulation of nuclear SMAD2/3 signaling
(Consensus)
Recessive Scores
- pRec
- 0.152
Haploinsufficiency Scores
- pHI
- 0.208
- hipred
- Y
- hipred_score
- 0.783
- ghis
- 0.590
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ski
- Phenotype
- cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); neoplasm; embryo phenotype;
Zebrafish Information Network
- Gene name
- skia
- Affected structure
- bulbus arteriosus
- Phenotype tag
- abnormal
- Phenotype quality
- amorphous
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;neural tube closure;lens morphogenesis in camera-type eye;transcription, DNA-templated;transforming growth factor beta receptor signaling pathway;cell population proliferation;negative regulation of cell population proliferation;anterior/posterior axis specification;negative regulation of Schwann cell proliferation;myotube differentiation;olfactory bulb development;myelination in peripheral nervous system;positive regulation of Wnt signaling pathway;embryonic limb morphogenesis;BMP signaling pathway;negative regulation of transforming growth factor beta receptor signaling pathway;negative regulation of BMP signaling pathway;negative regulation of histone deacetylation;negative regulation of activin receptor signaling pathway;somatic stem cell population maintenance;camera-type eye development;positive regulation of DNA binding;nose morphogenesis;negative regulation of cell differentiation;negative regulation of osteoblast differentiation;positive regulation of transcription by RNA polymerase II;negative regulation of fibroblast proliferation;camera-type eye morphogenesis;neuron development;skeletal muscle fiber development;cell motility;roof of mouth development;retina development in camera-type eye;face morphogenesis;bone morphogenesis;SMAD protein signal transduction;protein homotrimerization
- Cellular component
- nucleus;nucleoplasm;transcription factor complex;cytoplasm;centrosome;nuclear body;PML body;transcriptional repressor complex;protein-containing complex
- Molecular function
- DNA-binding transcription factor activity, RNA polymerase II-specific;transcription corepressor activity;protein binding;zinc ion binding;protein kinase binding;protein domain specific binding;ubiquitin protein ligase binding;SMAD binding;histone deacetylase inhibitor activity;repressing transcription factor binding