SOX10

Summary

SOX10 (SRY-box transcription factor 10, HGNC:11190) is a protein-coding gene on chromosome 22q13.1, encoding Transcription factor SOX-10 (P56693). Transcription factor that plays a central role in developing and mature glia. In precision oncology, SOX10 Loss is associated with resistance to Vemurafenib in Melanoma (CIViC Level D). It is a selective cancer dependency (DepMap: 16.7% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional activator after forming a protein complex with other proteins. This protein acts as a nucleocytoplasmic shuttle protein and is important for neural crest and peripheral nervous system development. Mutations in this gene are associated with Waardenburg-Shah and Waardenburg-Hirschsprung disease.

Source: NCBI Gene 6663 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Waardenburg syndrome type 4C (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 1 total
• Phenotypes (HPO): 140
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer dependency (DepMap): dependent in 16.7% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 46 downstream targets (CollecTRI)
• MANE Select transcript: NM_006941

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11190
Approved symbol	SOX10
Name	SRY-box transcription factor 10
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	DOM, WS4, WS2E, SOX-10
Ensembl gene	ENSG00000100146
Ensembl biotype	protein_coding
OMIM	602229
Entrez	6663

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000360880, ENST00000396884, ENST00000427770, ENST00000446929, ENST00000470555, ENST00000651746, ENST00000652356, ENST00000690831, ENST00000698177, ENST00000851529

RefSeq mRNA: 1 — MANE Select: NM_006941 NM_006941

CCDS: CCDS13964

Canonical transcript exons

ENST00000396884 — 4 exons

Exon	Start	End
ENSE00000654130	37977867	37978135
ENSE00003848621	37972312	37974198
ENSE00003848892	37984339	37984555
ENSE00003972902	37983357	37983868

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 98.87.

FANTOM5 (CAGE): breadth broad, TPM avg 13.2824 / max 829.5780, expressed in 349 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194109	13.2773	349
194108	0.0051	3

Top tissues by expression

286 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
inferior olivary complex	UBERON:0002127	98.87	gold quality
sural nerve	UBERON:0015488	98.86	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.71	gold quality
inferior vagus X ganglion	UBERON:0005363	98.59	gold quality
tibial nerve	UBERON:0001323	98.26	gold quality
trigeminal ganglion	UBERON:0001675	98.13	gold quality
dorsal root ganglion	UBERON:0000044	97.88	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.84	gold quality
spinal cord	UBERON:0002240	97.76	gold quality
medulla oblongata	UBERON:0001896	97.47	gold quality
subthalamic nucleus	UBERON:0001906	97.45	gold quality
ventral tegmental area	UBERON:0002691	97.16	gold quality
parotid gland	UBERON:0001831	97.12	gold quality
lateral globus pallidus	UBERON:0002476	96.69	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.32	gold quality
superior vestibular nucleus	UBERON:0007227	96.23	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.11	gold quality
olfactory bulb	UBERON:0002264	95.92	gold quality
CA1 field of hippocampus	UBERON:0003881	95.64	gold quality
midbrain	UBERON:0001891	95.41	gold quality
substantia nigra	UBERON:0002038	95.23	gold quality
middle frontal gyrus	UBERON:0002702	95.08	gold quality
amygdala	UBERON:0001876	94.42	gold quality
putamen	UBERON:0001874	94.24	gold quality
globus pallidus	UBERON:0001875	94.04	gold quality
substantia nigra pars compacta	UBERON:0001965	94.00	gold quality
pons	UBERON:0000988	93.85	gold quality
Ammon’s horn	UBERON:0001954	93.68	gold quality
medial globus pallidus	UBERON:0002477	93.22	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.06	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	377.51
E-HCAD-56	yes	268.88
E-MTAB-9435	yes	212.04
E-GEOD-135922	yes	22.70
E-ANND-3	yes	4.67

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

46 targets.

Target	Regulation
ADAM2
ASCL1	Unknown
BEST1	Activation
CHRNA10
CHRNA2
CHRNA3
CHRNB4
CNTF	Repression
COL11A2	Activation
COL2A1	Activation
COMMD7
DCT	Repression
DHH
EDNRB	Unknown
EGR2	Activation
ERBB3	Unknown
GJB1	Activation
GJC2	Unknown
GNAS
JAG1	Activation
L1CAM	Unknown
MAG	Unknown
MBP	Unknown
MET	Activation
MIA	Activation
MITF	Activation
MPZ	Unknown
NES	Unknown
NKX2-2	Activation
PDGFRA	Unknown

JASPAR motifs

Motif	Name	Family
MA0442.1	SOX10	SOX-related factors
MA0442.2	SOX10	SOX-related factors
MA0442.3	SOX10	SOX-related factors

JASPAR matrix evidence (PMIDs): PMID:17916232

Upstream regulators (CollecTRI, top): CTNNB1, EGR2, OLIG2, PAX3, RBPJ, SOX10, SOX9

miRNA regulators (miRDB)

88 targeting SOX10, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4666A-5P	99.41	69.72	1887

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 16.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• novel mutations suggest a dominant negative role in Waardenburg-Shah syndrome (PMID:11546831)
• Results show that the inhibition of the nuclear export of Sox10 led to decreased transactivation of transfected reporters and endogenous target genes, arguing that continuous nucleocytoplasmic shuttling is essential for the function of Sox10. (PMID:12138193)
• Muations in SOX10 is associated with chronic intestinal pseudo-abstruction (PMID:12189494)
• SOX10 mutation carriers in Hirschsprung’s disease had a very long histologic transition and exhibited no gut caliber change (PMID:12720173)
• SOX10 modulates alpha-melanocyte-stimulating hormone-triggered expression of microphthalmia-associated transcription factor in melanocytes (PMID:12944398)
• The lack of normal SOX10 mediated activation of RET transcription may lead to intestinal aganglionosis, overexpression of genes coding for structural myelin proteins (PMID:14523991)
• phenotype of Sox10Dom/+ mutants ranges over a continuum from severe aganglionosis to no detectable phenotype in the gut (PMID:15843399)
• The SOX10 is highly expressed in unpigmented melanocyte precursors but are down-regulated upon differentiation. (PMID:15896776)
• DNA methylation status of the SOX10 CpG island could be an epigenetic sign of oligodendrocyte dysfunction in schizophrenia. (PMID:15930386)
• the transcriptional factor SOX10 is one of the key determinants of oligodendroglial differentiation (PMID:16205963)
• identified an association of Sox10 with the N-myc interactor Nmi, which was mediated by the high-mobility group of Sox10 and the central region of Nmi; Nmi modulated the transcriptional activity of Sox10 (PMID:16214168)
• SOX10 protein is modified by sumoylation; three sumoylation consensus sites were found in the SOX10 protein, all of them are functional and modulate SOX10 activity. (PMID:16494873)
• Results show that genetic variations in the SOX10 gene do not contribute to susceptibility to Japanese schizophrenia. (PMID:16741945)
• pediatric and adult high grade tumors display strong nuclear staining for SOX10 (PMID:16791471)
• Sox10-regulated ErbB3 overexpression is a novel insight into the biology of pilocytic astrocytoma. (PMID:16896310)
• SOX10 gene is related to the development of schizophrenia in a Japanese population. (PMID:17621166)
• Failure to properly terminate SOX10 translation causes the generation of a deleterious functional domain that occurs because of translation of the normal 3’-UTR; the mutant fusion protein causes a severe neurological disease. (PMID:17855451)
• investigation of the expression of Sox10 in other human tumors and in a number of gliomas. Sox10 expression was restricted to gliomas and melanomas. (PMID:17855658)
• Neurological phenotypes reminiscent of that observed in Waardenburg syndrome types 2 affected patients with SOX10 deletions. (PMID:17999358)
• A SOX10 “de novo” splice site mutation (c.698-2A > C) was identified in a severe type 4 Waardenburg syndrome without Hirschsprung disease. (PMID:18348267)
• A de novo missense mutation in the gene encoding the SOX10 transcription factor in a Spanish sporadic case of Waardenburg syndrome type IV. (PMID:18348274)
• Quantitative changes of enteric glia represented by SOX10 provide a basis for pathological assessment of glial proliferation and/or degeneration in the diseased gut. (PMID:18512230)
• Waardenburg syndrome type II is caused by a heterozygous SOX10 frameshift mutation. (PMID:18627047)
• Sox10 will serve as a more sensitive and specific marker for the diagnosis of melanocytic and schwannian tumors than S100 protein. (PMID:18636017)
• Multiple sites belonging to 4 different genes (proteolipid protein, Sox10, extracellular superoxide dismutase, and pleiotrophin) were shown to directly interact with Sox10 by chromatin immunoprecipitation assay. (PMID:18786246)
• SOX9 and SOX10 but not BRN2 seem to be required for nestin expression in human melanoma. (PMID:18923447)
• Report on spanish cases of Waardenburg syndrome type 4 with novel mutations in EDN3 and SOX 10 genes. (PMID:19764030)
• Sox10 can be reliably used for melanoma detection in sentinel lymph nodes. (PMID:19912373)
• The degree of sex reversal correlated with levels of Sox10 expression in different transgenic lines. (PMID:19933217)
• The SOX10 plays an active role in melanoma cells by regulating the MET gene. (PMID:20067553)
• The study describes the evaluation of the SOX10 gene in a series of 196 isolated Hirschsprung disease cases and reports a truncating c.153-155del mutation. (PMID:20130826)
• in ovo electroporation in the developing neural tube of chicken was used to determine which regions and properties of SOX10 are required for early neural crest development. (PMID:20308050)
• Seven new mutations in PAX3, MITF, and SOX10 genes in 11 families with type I or type II Waardenburg syndrome were identified. (PMID:20478267)
• Our results showed that SOX10 was strongly expressed by desmoplastic melanoma. (PMID:20653825)
• SOX10 downregulation resulted in variable effects on proliferation and migration rates in the melanoma cell lines. In conclusion, the SOX10 intensity level differed depending on the tissue studied and SOX10 might have a role in survival. (PMID:20890226)
• This database focuses on the transcription factor SOX10, which has essential roles in pigment cell development and function. (PMID:20974870)
• Two novel heterozygous mutations (c.254G>A and c.698-2A>T) in the SOX10 gene were detected in Chinese patients with type IV Waardenburg syndrome. (PMID:21531202)
• Sox-10 is useful in identifying nodal metastases in melanoma (PMID:21552103)
• Novel SOX10 missense mutations were found in 11 patients and were shown to be associated with various phenotypes of Waardenburg syndrome, ranging from WS2 to P. (PMID:21898658)
• Here, we further identified an E248fsX30 SOX10 mutation in a family of WS2. (PMID:21965087)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	sox10	ENSDARG00000077467
mus_musculus	Sox10	ENSMUSG00000033006
rattus_norvegicus	Sox10	ENSRNOG00000011305
drosophila_melanogaster	Sox14	FBGN0005612
drosophila_melanogaster	Sox21a	FBGN0036411
drosophila_melanogaster	Sox102F	FBGN0039938
caenorhabditis_elegans		WBGENE00001182

Paralogs (20): SOX8 (ENSG00000005513), SOX30 (ENSG00000039600), SOX6 (ENSG00000110693), SOX4 (ENSG00000124766), SOX21 (ENSG00000125285), SOX9 (ENSG00000125398), SOX15 (ENSG00000129194), SOX5 (ENSG00000134532), SOX3 (ENSG00000134595), SOX13 (ENSG00000143842), SOX17 (ENSG00000164736), SOX14 (ENSG00000168875), SOX7 (ENSG00000171056), SOX11 (ENSG00000176887), SOX12 (ENSG00000177732), CFAP65 (ENSG00000181378), SOX2 (ENSG00000181449), SOX1 (ENSG00000182968), SRY (ENSG00000184895), SOX18 (ENSG00000203883)

Protein

Protein identifiers

Transcription factor SOX-10 — P56693 (reviewed: P56693)

All UniProt accessions (6): P56693, A0A494C0R1, A0A8I5KW15, A0A8V8TM01, A6PVD3, H0Y5N4

UniProt curated annotations — full annotation on UniProt →

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. Transcriptional activator of MBP, via binding to the gene promoter.

Subunit / interactions. Monomer. Interacts with ARMCX3 at the mitochondrial outer membrane surface. Interacts with PAX3.

Subcellular location. Cytoplasm. Nucleus. Mitochondrion outer membrane.

Tissue specificity. Expressed in fetal brain and in adult brain, heart, small intestine and colon.

Disease relevance. Waardenburg syndrome 2E (WS2E) [MIM:611584] An autosomal dominant auditory-pigmentary disorder characterized by sensorineural deafness, pigmentary disturbances of the hair, skin and eyes, and absence of dystopia canthorum which is the lateral displacement of the inner canthus of each eye. Individuals with WS2E may have neurologic abnormalities, including mental impairment, myelination defects, and ataxia. Some patients can manifest features of Kallmann syndrome. The disease is caused by variants affecting the gene represented in this entry. 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). The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The transactivation domains TAM and TAC (for transactivation domain in the middle and at the C-terminus, respectively) are required to contact transcriptional coactivators and basal transcriptional machinery components and thereby induce gene transactivation.

Isoforms (2)

UniProt ID	Names	Canonical?
P56693-1	1	yes
P56693-2	2

RefSeq proteins (1): NP_008872* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009071	HMG_box_dom	Domain
IPR022151	Sox_N	Domain
IPR036910	HMG_box_dom_sf	Homologous_superfamily
IPR050917	SOX_TF	Family

Pfam: PF00505, PF12444

UniProt features (38 total): sequence variant 19, region of interest 8, compositionally biased region 4, sequence conflict 2, chain 1, DNA-binding region 1, short sequence motif 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56693-F1	57.32	0.17

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 24

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-9619665	EGR2 and SOX10-mediated initiation of Schwann cell myelination
R-HSA-9764302	Regulation of CDH19 Expression and Function
R-HSA-9824585	Regulation of MITF-M-dependent genes involved in pigmentation
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity
R-HSA-1266738	Developmental Biology
R-HSA-1500931	Cell-Cell communication
R-HSA-418990	Adherens junctions interactions
R-HSA-421270	Cell-cell junction organization
R-HSA-446728	Cell junction organization
R-HSA-9675108	Nervous system development
R-HSA-9730414	MITF-M-regulated melanocyte development
R-HSA-9759476	Regulation of Homotypic Cell-Cell Adhesion
R-HSA-9764260	Regulation of Expression and Function of Type II Classical Cadherins
R-HSA-9856651	MITF-M-dependent gene expression

MSigDB gene sets: 557 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, CREL_01, MODULE_52, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, MODY_HIPPOCAMPUS_POSTNATAL, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_NEGATIVE_REGULATION_OF_GLIOGENESIS, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_GROWTH, GOBP_GLIAL_CELL_DEVELOPMENT, AREB6_01, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_MYELINATION

GO Biological Process (36): negative regulation of transcription by RNA polymerase II (GO:0000122), in utero embryonic development (GO:0001701), neural crest cell migration (GO:0001755), morphogenesis of an epithelium (GO:0002009), positive regulation of neuroblast proliferation (GO:0002052), regulation of transcription by RNA polymerase II (GO:0006357), transcription elongation by RNA polymerase II (GO:0006368), neuroblast proliferation (GO:0007405), peripheral nervous system development (GO:0007422), anatomical structure morphogenesis (GO:0009653), negative regulation of Schwann cell proliferation (GO:0010626), positive regulation of gene expression (GO:0010628), oligodendrocyte development (GO:0014003), positive regulation of gliogenesis (GO:0014015), central nervous system myelination (GO:0022010), melanocyte differentiation (GO:0030318), positive regulation of myelination (GO:0031643), lacrimal gland development (GO:0032808), negative regulation of apoptotic process (GO:0043066), positive regulation of DNA-templated transcription (GO:0045893), cell maturation (GO:0048469), enteric nervous system development (GO:0048484), digestive tract morphogenesis (GO:0048546), developmental growth (GO:0048589), oligodendrocyte differentiation (GO:0048709), morphogenesis of a branching epithelium (GO:0061138), cellular response to progesterone stimulus (GO:0071393), cellular response to xenobiotic stimulus (GO:0071466), negative regulation of canonical Wnt signaling pathway (GO:0090090), regulation of DNA-templated transcription (GO:0006355), transcription by RNA polymerase II (GO:0006366), cell differentiation (GO:0030154), developmental process (GO:0032502), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), stem cell differentiation (GO:0048863)

GO Molecular Function (13): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity (GO:0001216), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), identical protein binding (GO:0042802), DNA-binding transcription factor binding (GO:0140297), sequence-specific double-stranded DNA binding (GO:1990837), promoter-specific chromatin binding (GO:1990841), chromatin binding (GO:0003682), protein binding (GO:0005515)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrial outer membrane (GO:0005741), cytoplasm (GO:0005737), mitochondrion (GO:0005739), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
MITF-M-regulated melanocyte development	2
Developmental Biology	2
Nervous system development	1
Regulation of Expression and Function of Type II Classical Cadherins	1
MITF-M-dependent gene expression	1
Cell-cell junction organization	1
Cell junction organization	1
Cell-Cell communication	1
Adherens junctions interactions	1
Regulation of Homotypic Cell-Cell Adhesion	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
positive regulation of neurogenesis	2
myelination	2
DNA-binding transcription factor activity	2
transcription cis-regulatory region binding	2
binding	2
intracellular membrane-bounded organelle	2
negative regulation of DNA-templated transcription	1
chordate embryonic development	1
neural crest cell development	1
mesenchymal cell migration	1
tissue morphogenesis	1
epithelium development	1
neuroblast proliferation	1
regulation of neuroblast proliferation	1
positive regulation of neural precursor cell proliferation	1
DNA-templated transcription elongation	1
generation of neurons	1
neural precursor cell proliferation	1
nervous system development	1
system development	1
developmental process	1
anatomical structure development	1
regulation of Schwann cell proliferation	1
Schwann cell proliferation	1
negative regulation of glial cell proliferation	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
glial cell development	1
oligodendrocyte differentiation	1
regulation of gliogenesis	1
gliogenesis	1
oligodendrocyte development	1
axon ensheathment in central nervous system	1
pigment cell differentiation	1

Protein interactions and networks

STRING

3404 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SOX10	PAX3	P23760	993
SOX10	MITF	O75030	938
SOX10	NFATC4	Q14934	919
SOX10	EDNRB	P24530	901
SOX10	OLIG2	Q13516	875
SOX10	EDN3	P14138	870
SOX10	TYR	P14679	869
SOX10	EGR2	P11161	860
SOX10	OLIG1	Q8TAK6	859
SOX10	SNAI2	O43623	842
SOX10	NMI	Q13287	837
SOX10	DCT	P40126	829
SOX10	GFRA1	P56159	823
SOX10	GDNF	P39905	802
SOX10	RET	P07949	793

IntAct

86 interactions, top by confidence:

A	B	Type	Score
CRX	SOX10	psi-mi:“MI:0915”(physical association)	0.560
SOX10	POU6F2	psi-mi:“MI:0915”(physical association)	0.560
SOX10	HSF4	psi-mi:“MI:0915”(physical association)	0.560
SOX10	MAGED1	psi-mi:“MI:0915”(physical association)	0.560
SOX10	DAZAP2	psi-mi:“MI:0915”(physical association)	0.560
SOX10	C10orf55	psi-mi:“MI:0915”(physical association)	0.560
SOX10	PPIA	psi-mi:“MI:0915”(physical association)	0.560
SOX10	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
SOX10	YWHAG	psi-mi:“MI:0915”(physical association)	0.560
SOX10	SETDB1	psi-mi:“MI:0915”(physical association)	0.560
SOX10	KAT5	psi-mi:“MI:0915”(physical association)	0.560
LMO3	SOX10	psi-mi:“MI:0915”(physical association)	0.560
SOX10	POU3F2	psi-mi:“MI:0915”(physical association)	0.530
SOX10	SOX10	psi-mi:“MI:0915”(physical association)	0.530
SOX10	PAX3	psi-mi:“MI:0915”(physical association)	0.530
SOX10	PAX3	psi-mi:“MI:0407”(direct interaction)	0.530
SOX10	POU3F2	psi-mi:“MI:0407”(direct interaction)	0.530
SOX10	SOX10	psi-mi:“MI:0407”(direct interaction)	0.530

BioGRID (206): SOX10 (Affinity Capture-Western), FBXW7 (Affinity Capture-Western), SOX10 (Reconstituted Complex), SOX10 (Biochemical Activity), SOX10 (Affinity Capture-Western), CHD7 (Affinity Capture-Western), SOX10 (Reconstituted Complex), PAX3 (Reconstituted Complex), SOX10 (Affinity Capture-Western), SOX10 (Affinity Capture-MS), HSF4 (Two-hybrid), CRX (Two-hybrid), POU6F2 (Two-hybrid), MAGED1 (Two-hybrid), DAZAP2 (Two-hybrid)

ESM2 similar proteins: A4IIJ8, A5A763, B7ZR65, F1LYL9, O18896, O55170, P10071, P27782, P40650, P48434, P48436, P56178, P56693, P57074, P61753, P61754, P70056, P70062, P70063, P70064, Q04886, Q04887, Q04888, Q0VGT2, Q5IS56, Q61602, Q66JF1, Q6DFF5, Q6F2E7, Q6GL68, Q6IZ48, Q6VVD7, Q7YRJ7, Q800Q5, Q8AXX8, Q90ZB6, Q91660, Q91731, Q924A0, Q9BG89

Diamond homologs: A2TED3, A4IIJ8, A4QNG3, A5A763, A5D8R3, B0ZTE1, B0ZTE2, B3DLD3, B7ZR65, F1LYL9, O00570, O15370, O18896, O42342, O42569, O42601, O55170, O57401, O60248, O95416, P0C1G9, P35713, P35716, P40637, P40639, P40646, P40650, P40652, P40656, P40657, P43267, P43680, P47792, P48430, P48431, P48432, P48433, P48434, P48435, P48436

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
NMI	“up-regulates activity”	SOX10	binding
NMI	“down-regulates activity”	SOX10	binding
ERK1/2	“down-regulates activity”	SOX10	phosphorylation
GSK3B	“down-regulates quantity”	SOX10	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transcriptional and post-translational regulation of MITF-M expression and activity	5	33.0×	2e-04
Signaling by WNT	5	20.7×	5e-04
Cell Cycle, Mitotic	5	8.9×	5e-03
Cell Cycle	6	8.0×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cell migration	7	12.3×	3e-04

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

1 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

404 predictions. Top by Δscore:

Variant	Effect	Δscore
22:37974203:G:GC	acceptor_gain	1.0000
22:37974194:CTGGC:C	acceptor_gain	0.9900
22:37974196:GGC:G	acceptor_loss	0.9900
22:37974197:GCCT:G	acceptor_loss	0.9900
22:37974199:C:CC	acceptor_gain	0.9900
22:37974203:G:C	acceptor_gain	0.9900
22:37974215:C:CT	acceptor_gain	0.9900
22:37977862:CTCA:C	donor_loss	0.9900
22:37977863:TCA:T	donor_loss	0.9900
22:37977864:CACC:C	donor_loss	0.9900
22:37977865:A:AC	donor_gain	0.9900
22:37977865:ACCT:A	donor_loss	0.9900
22:37977866:C:A	donor_loss	0.9900
22:37977866:C:CC	donor_gain	0.9900
22:37978143:G:C	acceptor_gain	0.9900
22:37978154:C:CT	acceptor_gain	0.9900
22:37983351:GCTCA:G	donor_loss	0.9900
22:37983352:CTCA:C	donor_loss	0.9900
22:37983353:TCA:T	donor_loss	0.9900
22:37983354:CAC:C	donor_loss	0.9900
22:37983355:A:C	donor_loss	0.9900
22:37983355:ACCT:A	donor_gain	0.9900
22:37983356:C:CT	donor_loss	0.9900
22:37983356:CCTC:C	donor_gain	0.9900
22:37974195:TGGC:T	acceptor_gain	0.9800
22:37974216:A:T	acceptor_gain	0.9800
22:37977865:AC:A	donor_gain	0.9800
22:37977866:CC:C	donor_gain	0.9800
22:37978136:C:CC	acceptor_gain	0.9800
22:37978141:G:C	acceptor_gain	0.9800

AlphaMissense

3023 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:37978036:C:A	R176S	1.000
22:37978036:C:G	R176S	1.000
22:37978037:C:A	R176M	1.000
22:37978037:C:G	R176T	1.000
22:37978038:T:A	R176W	1.000
22:37978038:T:C	R176G	1.000
22:37978040:G:T	P175H	1.000
22:37978041:G:A	P175S	1.000
22:37978041:G:T	P175T	1.000
22:37978046:T:C	Y173C	1.000
22:37978046:T:G	Y173S	1.000
22:37978047:A:C	Y173D	1.000
22:37978047:A:G	Y173H	1.000
22:37978047:A:T	Y173N	1.000
22:37978048:C:A	K172N	1.000
22:37978048:C:G	K172N	1.000
22:37978049:T:A	K172M	1.000
22:37978050:T:C	K172E	1.000
22:37978052:T:C	Y171C	1.000
22:37978053:A:C	Y171D	1.000
22:37978053:A:G	Y171H	1.000
22:37978053:A:T	Y171N	1.000
22:37978062:G:C	H168D	1.000
22:37978069:C:A	K165N	1.000
22:37978069:C:G	K165N	1.000
22:37978071:T:C	K165E	1.000
22:37978072:G:C	H164Q	1.000
22:37978072:G:T	H164Q	1.000
22:37978073:T:A	H164L	1.000
22:37978073:T:C	H164R	1.000

dbSNP variants (sampled 300 via entrez): RS1000038348 (22:37984977 G>A,T), RS1000422643 (22:37979931 T>A), RS1000474971 (22:37979694 C>T), RS1001117637 (22:37972875 G>A), RS1001655214 (22:37980028 C>G), RS1001828333 (22:37973178 G>A), RS1002001294 (22:37980183 T>C), RS1002609890 (22:37978452 T>C), RS1002775621 (22:37975405 G>A), RS1002997364 (22:37975726 C>T), RS1003008153 (22:37975752 A>C,G), RS1003063105 (22:37981625 T>C), RS1003660327 (22:37983061 C>T), RS1003769412 (22:37977029 G>A), RS1003891184 (22:37975833 G>A)

Disease associations

OMIM: gene MIM:602229 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
PCWH syndrome	Definitive	Autosomal dominant
Waardenburg syndrome type 4C	Definitive	Autosomal dominant
Waardenburg syndrome type 2E	Definitive	Autosomal dominant
deaf blind hypopigmentation syndrome, Yemenite type	Definitive	Autosomal dominant
Kallmann syndrome	Supportive	Autosomal dominant
Waardenburg syndrome type 2	Supportive	Autosomal dominant
Waardenburg-Shah syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Waardenburg syndrome type 4C	Definitive	AD

Mondo (7): PCWH syndrome (MONDO:0012198), Waardenburg syndrome type 4C (MONDO:0013202), Waardenburg syndrome type 2E (MONDO:0012698), Kallmann syndrome (MONDO:0018800), Waardenburg syndrome type 2 (MONDO:0019517), Waardenburg-Shah syndrome (MONDO:0019518), deaf blind hypopigmentation syndrome, Yemenite type (MONDO:0011133)

Orphanet (0):

HPO phenotypes

140 total (30 of 140 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000054	Micropenis
HP:0000077	Abnormality of the kidney
HP:0000104	Renal agenesis
HP:0000135	Hypogonadism
HP:0000144	Decreased fertility
HP:0000175	Cleft palate
HP:0000365	Hearing impairment
HP:0000366	Abnormality of the nose
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae
HP:0000431	Wide nasal bridge
HP:0000458	Anosmia
HP:0000473	Torticollis
HP:0000478	Abnormality of the eye
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000522	Alacrima
HP:0000534	Abnormal eyebrow morphology
HP:0000545	Myopia
HP:0000551	Color vision defect
HP:0000633	Decreased lacrimation
HP:0000635	Blue irides

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002397_607	Mean spheric corpuscular volume	4.000000e-09

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D017436	Kallmann Syndrome	C12.050.351.875.253.096.750; C12.200.706.316.096.750; C12.800.316.096.750; C16.131.939.316.096.750; C16.320.467; C19.391.119.096.750; C19.391.482.600
C563789	Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease (supp.)
C567679	Waardenburg Syndrome, Type 4c (supp.)
C536463	Waardenburg syndrome type 2 (supp.)
C536771	Yemenite deaf-blind hypopigmentation syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
SOX10 Loss	Vemurafenib	Melanoma	Resistance	CIViC D	EID1710

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs139887	Toxicity	3	carboplatin;docetaxel;paclitaxel	Ovarian Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs139887	POLR2F, SOX10	3	3.00	1	carboplatin;docetaxel;paclitaxel

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression, increases methylation, affects cotreatment	6
trichostatin A	increases expression, affects cotreatment	3
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation	2
Nickel	decreases expression	2
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
Calcitriol	increases expression	1
Dexamethasone	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Etoposide	affects response to substance	1
Folic Acid	increases expression	1
Lead	decreases expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Tretinoin	affects cotreatment, increases expression	1
Cadmium Chloride	decreases expression	1

Cellosaurus cell lines

9 cell lines: 4 embryonic stem cell, 3 induced pluripotent stem cell, 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A6L1	SEES3-1V human SOX10, clone1	Embryonic stem cell	Male
CVCL_A6L2	SEES3-1V human SOX10, clone2	Embryonic stem cell	Male
CVCL_A6L3	SEES3-1V human SOX10, clone3	Embryonic stem cell	Male
CVCL_A9SY	IMAGINi022-A	Induced pluripotent stem cell	Female
CVCL_B0JR	WAe009-A-71	Embryonic stem cell	Female
CVCL_B5QQ	CPGHi005-A	Induced pluripotent stem cell	Male
CVCL_B8PW	Abcam HCT 116 SOX10 KO	Cancer cell line	Male
CVCL_B9SC	Abcam A-549 SOX10 KO	Cancer cell line	Male
CVCL_YP17	JTUi002-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

18 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01403532	PHASE4	COMPLETED	Sequential Therapy for Hypogonadotropic Hypogonadism
NCT02880280	PHASE4	UNKNOWN	Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin Treat Congenital Hypogonadotropic Hypogonadism
NCT03687606	PHASE4	UNKNOWN	Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH)
NCT00064987	PHASE2	TERMINATED	Follicle Stimulating Hormone (FSH) to Improve Testicular Development in Men With Hypogonadism
NCT00392756	PHASE1	COMPLETED	Examination of Idiopathic Hypogonadotropic Hypogonadism (IHH)and Kallmann Syndrome (KS)
NCT00493961	PHASE1	COMPLETED	Studying the Effects of 7 Days of Gonadotropin Releasing Hormone (GnRH) Treatment in Men With Hypogonadism
NCT00914823	PHASE1	COMPLETED	Kisspeptin Administration in the Adult
NCT01438034	PHASE1	COMPLETED	Kisspeptin in the Evaluation of Delayed Puberty
NCT03118479	PHASE1	TERMINATED	Effect of Varying Testosterone Levels on Insulin Sensitivity in Men With Idiopathic Hypogonadotropic Hypogonadism (IHH)
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT00392457	Not specified	COMPLETED	Investigating the Regulation of Reproductive Hormones in Adult Men
NCT00494169	Not specified	COMPLETED	Investigation of the Genetic Causes of Kallmann Syndrome and Reproductive Disorders
NCT00623116	Not specified	UNKNOWN	A Study to Characterize Epidemiology, Clinical and Genetic Features of Kallmann Syndrome in Finland
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT01914172	Not specified	COMPLETED	Health Needs of Patients With Kallmann Syndrome
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT04733274	Not specified	ACTIVE_NOT_RECRUITING	Patient and Healthcare Professional Views on Genetic/Genomic Information and Testing
NCT05971836	Not specified	ACTIVE_NOT_RECRUITING	The Molecular Basis of Inherited Reproductive Disorders