SOX10

SRY-box transcription factor 10, the group of SRY-box transcription factors

Basic information

Region (hg38): 22:37970685-37987422

Links

ENSG00000100146 ∙ NCBI:6663 ∙ OMIM:602229 ∙ HGNC:11190 ∙ Uniprot:P56693 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• PCWH syndrome (Strong), mode of inheritance: AD
• Waardenburg syndrome type 2E (Strong), mode of inheritance: AD
• Waardenburg syndrome type 4C (Strong), mode of inheritance: AD
• PCWH syndrome (Definitive), mode of inheritance: AD
• deaf blind hypopigmentation syndrome, Yemenite type (Definitive), mode of inheritance: AD
• Waardenburg syndrome type 2E (Definitive), mode of inheritance: AD
• Waardenburg syndrome type 4C (Definitive), mode of inheritance: AD
• Waardenburg syndrome type 4C (Definitive), mode of inheritance: AD
• Waardenburg syndrome type 2 (Supportive), mode of inheritance: AD
• Waardenburg-Shah syndrome (Supportive), mode of inheritance: AD
• Kallmann syndrome (Supportive), mode of inheritance: AD
• PCWH syndrome (Supportive), mode of inheritance: AD
• PCWH syndrome (Strong), mode of inheritance: AD
• Waardenburg syndrome type 4C (Definitive), mode of inheritance: AD
• Waardenburg syndrome type 2E (Strong), mode of inheritance: AD
• Waardenburg syndrome type 4C (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Waardenburg syndrome, type 4C; Waardenburg syndrome, type 2E; Peripheral demyelinating neuropathy, central dysmyelination, Waardenburg syndrome, and Hirschsprung disease; Hirschsprung disease, susceptibility to, 10	AD	Audiologic/Otolaryngologic; Gastrointestinal	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In some individuals (such as with Peripheral demyelinating neuropathy, central dysmyelination, Waardenburg syndrome, and Hirschsprung disease), awareness of potential GI complications (eg, chronic intestinal pseudoobstruction) may be beneficial to allow prompt and appropriate management	Audiologic/Otolaryngologic; Dermatologic; Gastrointestinal; Genitourinary; Neurologic; Ophthalmologic	8911608; 9462749; 10441344; 10077527; 12189494; 17999358; 18348267; 18627047; 22246888; 24357527
Variants affecting regulatory regions have been implicated in Hirschsprung disease

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SOX10 gene.

• not provided (210 variants)
• PCWH syndrome (51 variants)
• Waardenburg syndrome (41 variants)
• Waardenburg syndrome type 4C (34 variants)
• Waardenburg syndrome type 2E (33 variants)
• not specified (24 variants)
• Inborn genetic diseases (10 variants)
• SOX10-related condition (7 variants)
• Waardenburg syndrome type 2A (4 variants)
• Waardenburg syndrome type 4C;Waardenburg syndrome type 2E;PCWH syndrome (3 variants)
• Rare genetic deafness (3 variants)
• Deafness with anatomical inner ear anomalies (2 variants)
• PCWH syndrome;Waardenburg syndrome type 2E;Waardenburg syndrome type 4C (2 variants)
• Waardenburg syndrome type 1 (1 variants)
• Waardenburg syndrome type 2E, with neurologic involvement (1 variants)
• Hearing impairment (1 variants)
• SOX10-related disorder (1 variants)
• Hypogonadism with anosmia (1 variants)
• Intellectual disability (1 variants)
• Waardenburg syndrome type 4A (1 variants)
• Anosmia;Dominant congenital profound hearing loss (1 variants)
• PCWH syndrome;Waardenburg syndrome type 2E (1 variants)
• Waardenburg syndrome type 2E;Waardenburg syndrome type 4C;PCWH syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SOX10 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			5	52	4	61
missense	6	14	85	8	5	118
nonsense	22	8				30
start loss		1				1
frameshift	19	21	2			42
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)	2					2
splice region			1	3		4
non coding			13	11	14	38
Total	49	44	106	72	23

Variants in SOX10

This is a list of pathogenic ClinVar variants found in the SOX10 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-37972316-C-T		PCWH syndrome • Waardenburg syndrome	Uncertain significance (Jan 13, 2018)
22-37972407-GGA-G		Waardenburg syndrome • PCWH syndrome	Likely benign (Jun 14, 2016)
22-37972563-C-T		Waardenburg syndrome • PCWH syndrome	Likely benign (Apr 27, 2017)
22-37972665-C-G		Waardenburg syndrome • PCWH syndrome	Uncertain significance (Apr 27, 2017)
22-37972783-C-A		PCWH syndrome • Waardenburg syndrome	Uncertain significance (Jan 12, 2018)
22-37972784-G-A		Waardenburg syndrome • PCWH syndrome	Benign (Jan 13, 2018)
22-37972852-T-C		PCWH syndrome • Waardenburg syndrome	Uncertain significance (Jun 14, 2016)
22-37972927-A-T		Waardenburg syndrome • PCWH syndrome	Uncertain significance (Jan 13, 2018)
22-37972958-C-G		PCWH syndrome • Waardenburg syndrome	Benign (Jan 13, 2018)
22-37973020-C-T		Waardenburg syndrome • PCWH syndrome	Benign (Jan 12, 2018)
22-37973168-C-T		Waardenburg syndrome • PCWH syndrome	Uncertain significance (Jan 13, 2018)
22-37973337-T-C		PCWH syndrome • Waardenburg syndrome	Uncertain significance (Jan 12, 2018)
22-37973468-C-T		Waardenburg syndrome • PCWH syndrome	Benign (Jan 13, 2018)
22-37973484-CAGGGCCCCCTTT-C		PCWH syndrome	Likely pathogenic (Mar 22, 2022)
22-37973496-T-A		PCWH syndrome	Likely pathogenic (-)
22-37973497-A-G			Likely pathogenic (Sep 05, 2023)
22-37973516-AT-A		Waardenburg syndrome type 2E	Pathogenic (May 02, 2020)
22-37973519-T-C		SOX10-related disorder	Likely benign (Jun 21, 2019)
22-37973536-G-GTGTGGGGC		Waardenburg syndrome type 2E • PCWH syndrome;Waardenburg syndrome type 2E;Waardenburg syndrome type 4C	Pathogenic/Likely pathogenic (Apr 16, 2022)
22-37973543-G-A		not specified	Likely benign (Oct 31, 2022)
22-37973566-GGCTGGGGTCAGAGAT-G		Waardenburg syndrome type 4A	Pathogenic (Mar 07, 2018)
22-37973584-C-T			Benign (Aug 10, 2023)
22-37973585-C-T			Likely benign (Jul 06, 2022)
22-37973591-G-C			Likely benign (Dec 11, 2023)
22-37973598-C-T			Uncertain significance (Dec 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SOX10	protein_coding	protein_coding	ENST00000396884	3	16737

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.992	0.00834	121460	0	1	121461	0.00000412

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.77	166	301	0.551	0.0000195	2969
Missense in Polyphen		41	112.62	0.36405		1146
Synonymous	1.01	130	146	0.893	0.0000112	965
Loss of Function	3.51	0	14.3	0.00	6.53e-7	173

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000916	0.00000916
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor that plays a central role in developing and mature glia. Specifically activates expression of myelin genes, during oligodendrocyte (OL) maturation, such as DUSP15 and MYRF, thereby playing a central role in oligodendrocyte maturation and CNS myelination. Once induced, MYRF cooperates with SOX10 to implement the myelination program. Transcriptional activator of MITF, acting synergistically with PAX3 (PubMed:21965087). {ECO:0000250|UniProtKB:Q04888, ECO:0000269|PubMed:21965087}.
• Disease: DISEASE: Waardenburg syndrome 4C (WS4C) [MIM:613266]: A disorder characterized by the association of Waardenburg features (depigmentation and deafness) with the absence of enteric ganglia in the distal part of the intestine (Hirschsprung disease). {ECO:0000269|PubMed:18348274, ECO:0000269|PubMed:21898658, ECO:0000269|PubMed:9462749}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome and Hirschsprung disease (PCWH) [MIM:609136]: A complex neurocristopathy that includes features of 4 distinct syndromes: peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome and Hirschsprung disease. {ECO:0000269|PubMed:10762540, ECO:0000269|PubMed:15004559, ECO:0000269|PubMed:19208381, ECO:0000269|PubMed:21898658}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Neural Crest Differentiation (Consensus)

Recessive Scores

• pRec: 0.451

Intolerance Scores

• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.04

Haploinsufficiency Scores

• pHI: 0.986
• hipred: Y
• hipred_score: 0.833
• ghis: 0.622

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.624

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sox10
• Phenotype: embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; normal 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); pigmentation phenotype; limbs/digits/tail 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); digestive/alimentary phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: sox10
• Affected structure: hematopoietic multipotent progenitor cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: in utero embryonic development;neural crest cell migration;morphogenesis of an epithelium;positive regulation of neuroblast proliferation;regulation of transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter;central nervous system development;peripheral nervous system development;anatomical structure morphogenesis;negative regulation of Schwann cell proliferation;oligodendrocyte development;positive regulation of gliogenesis;central nervous system myelination;melanocyte differentiation;positive regulation of myelination;lacrimal gland development;negative regulation of apoptotic process;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;cell maturation;enteric nervous system development;digestive tract morphogenesis;developmental growth;oligodendrocyte differentiation;morphogenesis of a branching epithelium;cellular response to progesterone stimulus;negative regulation of canonical Wnt signaling pathway
• Cellular component: chromatin;nucleus;nucleoplasm;extrinsic component of mitochondrial outer membrane
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;transcription coactivator activity;protein binding;transcription factor binding;identical protein binding;promoter-specific chromatin binding