SOX6

SRY-box transcription factor 6, the group of SRY-box transcription factors|MicroRNA protein coding host genes

Basic information

Region (hg38): 11:15966449-16739591

Links

ENSG00000110693 ∙ NCBI:55553 ∙ OMIM:607257 ∙ HGNC:16421 ∙ Uniprot:P35712 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Tolchin-Le Caignec syndrome (Strong), mode of inheritance: AD
• Tolchin-Le Caignec syndrome (Moderate), mode of inheritance: AD
• Tolchin-Le Caignec syndrome (Strong), mode of inheritance: AD
• Tolchin-Le Caignec syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tolchin-Le Caignec syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	32442410

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SOX6 gene.

• Tolchin-Le Caignec syndrome (5 variants)
• not provided (4 variants)
• Inborn genetic diseases (4 variants)
• Intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SOX6 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				16	4	20
missense		7	65	11	3	86
nonsense	6	3				9
start loss						0
frameshift	5	1	2			8
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	3	2	6
non coding			1	10	11	22
Total	11	11	68	37	18

Highest pathogenic variant AF is 0.00000662

Variants in SOX6

This is a list of pathogenic ClinVar variants found in the SOX6 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-15972812-G-T			Uncertain significance (May 11, 2022)
11-15972819-C-T			Uncertain significance (Feb 04, 2024)
11-15972830-C-T			Likely benign (Jul 06, 2021)
11-15972839-A-G			Benign (Sep 19, 2022)
11-15972848-G-A			Likely benign (May 05, 2023)
11-15972849-C-T		Inborn genetic diseases	Uncertain significance (Aug 11, 2022)
11-15972851-A-G			Likely benign (Jan 26, 2022)
11-15972914-C-G		Inborn genetic diseases	Likely benign (May 15, 2024)
11-15972962-G-GCTCT			Uncertain significance (Aug 23, 2019)
11-15972982-T-C			Uncertain significance (Aug 01, 2023)
11-15972990-G-C		Inborn genetic diseases	Uncertain significance (Jun 13, 2023)
11-15973029-G-C		SOX6-related disorder	Uncertain significance (Feb 07, 2024)
11-15973072-C-T		Tolchin-Le Caignec syndrome	Uncertain significance (Apr 04, 2024)
11-15986197-T-C		SOX6-related disorder	Benign/Likely benign (Jan 21, 2024)
11-15986206-C-A		SOX6-related disorder	Benign (Aug 21, 2022)
11-15986207-A-G		Inborn genetic diseases	Uncertain significance (Nov 30, 2022)
11-15986217-A-G			Uncertain significance (Jun 15, 2022)
11-15986218-C-T			Likely benign (Oct 01, 2022)
11-15986218-C-CTG			Uncertain significance (Jan 10, 2024)
11-15986234-C-T		Inborn genetic diseases	Uncertain significance (May 21, 2024)
11-15986243-C-T		Inborn genetic diseases	Uncertain significance (Jan 05, 2023)
11-15986305-C-T			Likely benign (May 15, 2022)
11-15986310-G-A		Tolchin-Le Caignec syndrome	Pathogenic (Aug 30, 2024)
11-15986313-G-A		Neurodevelopmental disorder	Likely pathogenic (Oct 19, 2020)
11-15986347-G-A			Likely benign (Mar 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SOX6	protein_coding	protein_coding	ENST00000396356	15	773144

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000157	125595	0	2	125597	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.93	339	455	0.746	0.0000262	5311
Missense in Polyphen		124	207.55	0.59744		2358
Synonymous	0.162	167	170	0.984	0.00000975	1560
Loss of Function	5.48	4	42.6	0.0939	0.00000222	471

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000291	0.0000291
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000881	0.00000881
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional activator. Binds specifically to the DNA sequence 5'-AACAAT-3'. Plays a key role in several developmental processes, including neurogenesis and skeleton formation.
• Pathway: NOTCH1 regulation of human endothelial cell calcification;Endochondral Ossification;Signaling by WNT;Signal Transduction;Deactivation of the beta-catenin transactivating complex;TCF dependent signaling in response to WNT (Consensus)

Recessive Scores

• pRec: 0.188

Intolerance Scores

• loftool: 0.00909
• rvis_EVS: -1.11
• rvis_percentile_EVS: 6.72

Haploinsufficiency Scores

• pHI: 0.559
• hipred: Y
• hipred_score: 0.725
• ghis: 0.574

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.372

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sox6
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; limbs/digits/tail 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); normal phenotype; 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); respiratory system phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: sox6
• Affected structure: fast muscle cell
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;cell morphogenesis;in utero embryonic development;regulation of transcription, DNA-templated;muscle organ development;post-embryonic development;gene silencing;oligodendrocyte cell fate specification;positive regulation of chondrocyte differentiation;cell fate commitment;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;astrocyte differentiation;erythrocyte development;cartilage development;cardiac muscle cell differentiation;positive regulation of cartilage development;cellular response to transforming growth factor beta stimulus;negative regulation of cardiac muscle cell differentiation;positive regulation of mesenchymal stem cell differentiation
• Cellular component: nucleus;nucleoplasm
• 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;DNA binding;DNA-binding transcription factor activity;protein binding;protein heterodimerization activity