SKI

SKI proto-oncogene, the group of SKI transcriptional corepressors

Basic information

Region (hg38): 1:2227387-2310213

Links

ENSG00000157933 ∙ NCBI:6497 ∙ OMIM:164780 ∙ HGNC:10896 ∙ Uniprot:P12755 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Shprintzen-Goldberg 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 ClinVar and linked to the SKI gene.

• Shprintzen-Goldberg syndrome (597 variants)
• Familial thoracic aortic aneurysm and aortic dissection (418 variants)
• not provided (272 variants)
• not specified (94 variants)
• Inborn genetic diseases (26 variants)
• SKI-related condition (3 variants)
• Intellectual disability (3 variants)
• Isolated thoracic aortic aneurysm (3 variants)
• Disproportionate tall stature (3 variants)
• Neurodevelopmental disorder (2 variants)
• See cases (2 variants)
• Arterial dissection (1 variants)
• Intellectual disability;Joint laxity (1 variants)
• Autism spectrum disorder (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			9	339	4	352
missense	11	9	353	23		396
nonsense			4			4
start loss						0
frameshift	1	1	11			13
inframe indel	2		17			19
splice donor/acceptor (+/-2bp)			3			3
splice region			11	15		26
non coding			4	48	19	71
Total	14	10	401	410	23

Variants in SKI

This is a list of pathogenic ClinVar variants found in the SKI region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-2228718-G-T		not specified	Likely benign (Mar 07, 2018)
1-2228721-C-T			Likely benign (Mar 13, 2018)
1-2228725-G-A		not specified	Likely benign (Jan 16, 2017)
1-2228739-G-T		not specified	Likely benign (Jan 17, 2017)
1-2228740-G-GAGCGGC		not specified	Likely benign (Mar 30, 2017)
1-2228748-G-A		not specified	Likely benign (Jun 07, 2016)
1-2228756-C-G			Likely benign (Jun 07, 2018)
1-2228771-A-AGGC		Shprintzen-Goldberg syndrome	Uncertain significance (Aug 03, 2020)
1-2228774-C-A		Shprintzen-Goldberg syndrome	Uncertain significance (Feb 17, 2023)
1-2228774-C-G		Shprintzen-Goldberg syndrome	Uncertain significance (Dec 02, 2022)
1-2228774-C-T		Shprintzen-Goldberg syndrome • Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Dec 16, 2023)
1-2228775-G-C		Shprintzen-Goldberg syndrome • Familial thoracic aortic aneurysm and aortic dissection	Likely benign (Dec 25, 2022)
1-2228776-G-C		Shprintzen-Goldberg syndrome	Uncertain significance (Aug 14, 2020)
1-2228777-C-T		Shprintzen-Goldberg syndrome	Uncertain significance (Sep 19, 2022)
1-2228778-G-A		Familial thoracic aortic aneurysm and aortic dissection	Likely benign (Nov 23, 2023)
1-2228779-G-A			Uncertain significance (Dec 31, 2019)
1-2228778-G-GGCAGGCGGCC			Uncertain significance (May 22, 2018)
1-2228781-A-G		Familial thoracic aortic aneurysm and aortic dissection	Likely benign (Oct 31, 2019)
1-2228785-G-A			Uncertain significance (Dec 03, 2019)
1-2228787-C-T		Familial thoracic aortic aneurysm and aortic dissection	Likely benign (Nov 10, 2022)
1-2228788-C-G		Shprintzen-Goldberg syndrome	Uncertain significance (Aug 16, 2023)
1-2228790-C-G		Familial thoracic aortic aneurysm and aortic dissection	Likely benign (Nov 15, 2020)
1-2228792-G-A			Uncertain significance (Jun 26, 2019)
1-2228793-C-A		Shprintzen-Goldberg syndrome	Likely benign (Jul 23, 2022)
1-2228793-C-G		Familial thoracic aortic aneurysm and aortic dissection	Likely benign (Apr 09, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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