SOX8

Summary

SOX8 (SRY-box transcription factor 8, HGNC:11203) is a protein-coding gene on chromosome 16p13.3, encoding Transcription factor SOX-8 (P57073). Transcription factor that may play a role in central nervous system, limb and facial development.

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 may be involved in brain development and function. Haploinsufficiency for this protein may contribute to the cognitive disability found in an alpha-thalassemia-related syndrome (ART-16). This protein is also highly expressed in the majority of human hepatocellular carcinomas and promotes cellular proliferation and enhanced tumor growth.

Source: NCBI Gene 30812 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 118 total
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_014587

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11203
Approved symbol	SOX8
Name	SRY-box transcription factor 8
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000005513
Ensembl biotype	protein_coding
OMIM	605923
Entrez	30812

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000293894, ENST00000566034, ENST00000711625, ENST00000711626, ENST00000711627, ENST00000711628

RefSeq mRNA: 1 — MANE Select: NM_014587 NM_014587

CCDS: CCDS10428

Canonical transcript exons

ENST00000293894 — 3 exons

Exon	Start	End
ENSE00004016233	983728	983960
ENSE00004016234	984701	986979
ENSE00004016237	981770	982344

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 97.83.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4970 / max 112.0394, expressed in 271 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152017	1.4970	271

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	97.83	gold quality
lateral globus pallidus	UBERON:0002476	97.54	gold quality
subthalamic nucleus	UBERON:0001906	96.88	gold quality
parotid gland	UBERON:0001831	96.55	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.27	gold quality
ventral tegmental area	UBERON:0002691	96.22	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.16	gold quality
medulla oblongata	UBERON:0001896	96.12	gold quality
spinal cord	UBERON:0002240	96.06	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.99	gold quality
midbrain	UBERON:0001891	95.48	gold quality
substantia nigra	UBERON:0002038	95.43	gold quality
superior vestibular nucleus	UBERON:0007227	95.04	gold quality
putamen	UBERON:0001874	94.87	gold quality
globus pallidus	UBERON:0001875	94.55	gold quality
postcentral gyrus	UBERON:0002581	94.30	gold quality
parietal lobe	UBERON:0001872	94.11	gold quality
Ammon’s horn	UBERON:0001954	94.10	gold quality
amygdala	UBERON:0001876	94.06	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.80	gold quality
nucleus accumbens	UBERON:0001882	93.71	gold quality
corpus callosum	UBERON:0002336	93.70	gold quality
medial globus pallidus	UBERON:0002477	93.70	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.63	gold quality
caudate nucleus	UBERON:0001873	93.58	gold quality
substantia nigra pars compacta	UBERON:0001965	93.45	gold quality
trigeminal ganglion	UBERON:0001675	93.40	gold quality
tibia	UBERON:0000979	93.37	gold quality
temporal lobe	UBERON:0001871	93.26	gold quality
dorsal root ganglion	UBERON:0000044	92.88	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9435	yes	500.95
E-GEOD-84465	yes	25.30
E-GEOD-93593	yes	4.16
E-ANND-3	no	1.92

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
AMH	Unknown
BEST1
CLDN23
MYOG	Repression
VNN1	Activation

JASPAR motifs

Motif	Name	Family
MA0868.1	SOX8	SOX-related factors
MA0868.2	SOX8	SOX-related factors
MA0868.3	SOX8	SOX-related factors

JASPAR matrix evidence (PMIDs): PMID:12920151, PMID:17599239

Upstream regulators (CollecTRI, top): GLI2

miRNA regulators (miRDB)

73 targeting SOX8, 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-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-12124	99.68	69.17	2700

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 21)

• Quantitative changes of enteric glia represented by SOX8 provide a basis for pathological assessment of glial proliferation and/or degeneration in the diseased gut. (PMID:18512230)
• SOX2 and SOX17 expression patterns can distinguish between seminoma and embryonal carcinoma, and this distinction may be diagnostically useful. (PMID:19369635)
• The SOX8 single nucleotide polymorphism, rs2744148, is associated with increased genetic risk for multiple sclerosis. (PMID:23739915)
• SOX8 mRNA levels decrease during in vitro dedifferentiation of human articular chondrocytes and increase during chondrogenic differentiation of mesenchymal stromal cells. (PMID:24449344)
• SOX8 promotes cancer cell proliferation and its expression is correlated with elevated beta-catenin levels in hepatocellular carcinoma (PMID:24643625)
• Suggest that miRNA-124 may regulate non-small cell lung carcinoma cell proliferation via decreasing SOX8. (PMID:25400731)
• SOX8 bounds to the promoter region of FZD7 and induces the FZD7-mediated activation of the Wnt/beta-catenin pathway and confers chemoresistance and stemness properties and mediates epithelial mesenchymal transition in chemoresistant tongue squamous cell carcinoma. (PMID:29071717)
• These data demonstrate that SOX8 plays an important role in human reproduction and SOX8 mutations contribute to a spectrum of phenotypes including 46, XY DSD, male infertility and 46, XX POI. (PMID:29373757)
• High SOX8 expression is associated with progression of triple-negative breast cancer. (PMID:30810729)
• These observations demonstrate that Sox8 is a novel player essential for the differentiation of M cells and antigen-specific IgA response in the gut. (PMID:30877171)
• A transactivation domain in the middle of the proteins (TAM) synergizes with a C-terminal one (TAC). TAM comprises amphipathic alpha-helices predicted to form a protein-binding pocket and overlapping with minimal transactivation motifs (9-aa-TAD). One 9-aa-TAD sequence includes an evolutionarily conserved and functionally required EPhi[D/E]QYPhi motif. (PMID:31194875)
• SOX8 is over-expressed in patients with high T stage, which affects the outcome of prognosis in CRC patients. High expression of SOX8 usually has a poor independent prognostic factor for CRC. (PMID:31277140)
• Variation analysis of SOX8 gene in Chinese men with non-obstructive azoospermia or oligozoospermia. (PMID:32048324)
• High SOX8 expression promotes tumor growth and predicts poor prognosis through GOLPH3 signaling in tongue squamous cell carcinoma. (PMID:32307911)
• Aurora-A/SOX8/FOXK1 signaling axis promotes chemoresistance via suppression of cell senescence and induction of glucose metabolism in ovarian cancer organoids and cells. (PMID:32550913)
• Low expression of CircRNA HIPK3 promotes osteoarthritis chondrocyte apoptosis by serving as a sponge of miR-124 to regulate SOX8. (PMID:32767319)
• The oncogenic role of SOX8 in endometrial carcinoma. (PMID:33190587)
• Activation of RSK2 upregulates SOX8 to promote methotrexate resistance in gestational trophoblastic neoplasia. (PMID:34373588)
• SOX8 promotes cetuximab resistance via HGF/MET bypass pathway activation in colorectal cancer. (PMID:35195773)
• SOX8 Knockdown Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer by Inhibiting the Notch Signaling Pathway. (PMID:36246971)
• Additional evidence for the role of chromosomal imbalances and SOX8, ZNRF3 and HHAT gene variants in early human testis development. (PMID:36631813)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	sox8b	ENSDARG00000037782
danio_rerio	sox8a	ENSDARG00000105301
mus_musculus	Sox8	ENSMUSG00000024176
rattus_norvegicus	Sox8	ENSRNOG00000018841
drosophila_melanogaster	Sox14	FBGN0005612
drosophila_melanogaster	Sox21a	FBGN0036411
drosophila_melanogaster	Sox102F	FBGN0039938
caenorhabditis_elegans		WBGENE00001182
caenorhabditis_elegans		WBGENE00015716

Paralogs (20): SOX30 (ENSG00000039600), SOX10 (ENSG00000100146), 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-8 — P57073 (reviewed: P57073)

All UniProt accessions (4): P57073, A0AAA9YHI0, A0AAA9YHN4, A0AAA9YHU3

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that may play a role in central nervous system, limb and facial development. May be involved in male sex determination. Binds the consensus motif 5’-[AT][AT]CAA[AT]G-3'.

Subcellular location. Nucleus.

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. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

RefSeq proteins (1): NP_055402* (*=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 (16 total): region of interest 7, compositionally biased region 6, chain 1, DNA-binding region 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P57073-F1	59.57	0.16

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 254 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_METANEPHRIC_NEPHRON_MORPHOGENESIS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_URETER_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, GOBP_METANEPHROS_DEVELOPMENT, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_METANEPHRIC_EPITHELIUM_DEVELOPMENT, PEREZ_TP63_TARGETS, GOBP_POSITIVE_REGULATION_OF_KIDNEY_DEVELOPMENT, GOBP_SERTOLI_CELL_DEVELOPMENT

GO Biological Process (37): negative regulation of transcription by RNA polymerase II (GO:0000122), osteoblast differentiation (GO:0001649), in utero embryonic development (GO:0001701), neural crest cell migration (GO:0001755), morphogenesis of an epithelium (GO:0002009), signal transduction (GO:0007165), spermatogenesis (GO:0007283), peripheral nervous system development (GO:0007422), male gonad development (GO:0008584), positive regulation of gene expression (GO:0010628), regulation of hormone levels (GO:0010817), positive regulation of gliogenesis (GO:0014015), neural crest cell development (GO:0014032), positive regulation of osteoblast proliferation (GO:0033690), skeletal muscle cell differentiation (GO:0035914), negative regulation of apoptotic process (GO:0043066), cell fate commitment (GO:0045165), fat cell differentiation (GO:0045444), negative regulation of myoblast differentiation (GO:0045662), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of photoreceptor cell differentiation (GO:0046533), cell maturation (GO:0048469), enteric nervous system development (GO:0048484), oligodendrocyte differentiation (GO:0048709), Sertoli cell development (GO:0060009), astrocyte fate commitment (GO:0060018), retina development in camera-type eye (GO:0060041), retinal rod cell differentiation (GO:0060221), adipose tissue development (GO:0060612), morphogenesis of a branching epithelium (GO:0061138), renal vesicle induction (GO:0072034), ureter morphogenesis (GO:0072197), metanephric nephron tubule formation (GO:0072289), positive regulation of kidney development (GO:0090184), positive regulation of branching involved in ureteric bud morphogenesis (GO:0090190)

GO Molecular Function (8): 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 (GO:0003677), DNA-binding transcription factor binding (GO:0140297), sequence-specific double-stranded DNA binding (GO:1990837), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA-binding transcription factor activity (GO:0003700), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	4
regulation of transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription cis-regulatory region binding	2
cellular anatomical structure	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
ossification	1
chordate embryonic development	1
neural crest cell development	1
mesenchymal cell migration	1
tissue morphogenesis	1
epithelium development	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
developmental process involved in reproduction	1
male gamete generation	1
nervous system development	1
system development	1
gonad development	1
development of primary male sexual characteristics	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of biological quality	1
regulation of gliogenesis	1
gliogenesis	1
positive regulation of neurogenesis	1
neural crest cell differentiation	1
stem cell development	1
positive regulation of cell population proliferation	1
osteoblast proliferation	1
regulation of osteoblast proliferation	1
skeletal muscle tissue development	1
apoptotic process	1
regulation of apoptotic process	1

Protein interactions and networks

STRING

2190 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SOX8	OLIG1	Q8TAK6	657
SOX8	PAX3	P23760	650
SOX8	OLIG2	Q13516	624
SOX8	DMRT1	Q9Y5R6	604
SOX8	FOXL2	P58012	573
SOX8	WT1	P19544	558
SOX8	SOX11	P35716	525
SOX8	RSPO1	Q2MKA7	518
SOX8	SOX4	Q06945	512
SOX8	FOXD3	Q9UJU5	512
SOX8	AMH	P03971	497
SOX8	ID2	Q02363	487
SOX8	WNT4	P56705	487
SOX8	HBA1	P01922	479
SOX8	SMARCA4	P51532	467

IntAct

6 interactions, top by confidence:

A	B	Type	Score
HOXC11	SOX8	psi-mi:“MI:0915”(physical association)	0.370
MMP1	SOX8	psi-mi:“MI:0915”(physical association)	0.370
SOX8	NOD1	psi-mi:“MI:0915”(physical association)	0.370
PIDD1	SOX8	psi-mi:“MI:0915”(physical association)	0.370
SOX8	JAM2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (13): SOX8 (Affinity Capture-RNA), SOX8 (Proximity Label-MS), SOX8 (Proximity Label-MS), SOX8 (Proximity Label-MS), SOX8 (Proximity Label-MS), SOX8 (Affinity Capture-MS), SOX8 (Affinity Capture-MS), SOX8 (Two-hybrid), SOX8 (Affinity Capture-MS), SOX8 (Two-hybrid), SOX8 (Two-hybrid), SOX8 (Two-hybrid), SOX8 (Two-hybrid)

ESM2 similar proteins: A1YER7, A1YF08, A1YFD8, A1YFY3, A1YG85, A2D4P8, A2D4R4, A2D5I1, A2D649, A2T6H5, A2T6X6, A2T6Z0, A2T756, A2T7H5, A2T7J2, O35767, O43186, O88470, P06798, P09016, P10284, P10628, P17277, P17483, P18111, P23813, P31260, P31277, P31310, P42582, P43241, P43345, P47902, P52945, P52946, P52947, P52952, P57073, P58012, P70118

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

3 interactions.

A	Effect	B	Mechanism
AURKA	“up-regulates activity”	SOX8	phosphorylation
SOX8	“up-regulates quantity by expression”	FOXK2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	22
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

488 predictions. Top by Δscore:

Variant	Effect	Δscore
16:982340:TGGCG:T	donor_gain	1.0000
16:982341:GGCG:G	donor_gain	1.0000
16:982341:GGCGG:G	donor_gain	1.0000
16:982342:GCG:G	donor_gain	1.0000
16:982342:GCGG:G	donor_gain	1.0000
16:982345:G:GA	donor_loss	1.0000
16:982345:G:GG	donor_gain	1.0000
16:982346:T:A	donor_loss	1.0000
16:984695:CCCCA:C	acceptor_loss	1.0000
16:984696:CCCA:C	acceptor_loss	1.0000
16:984697:CCAGG:C	acceptor_loss	1.0000
16:984698:CA:C	acceptor_loss	1.0000
16:984699:A:AG	acceptor_gain	1.0000
16:984699:AG:A	acceptor_gain	1.0000
16:984700:G:GG	acceptor_gain	1.0000
16:984700:GG:G	acceptor_gain	1.0000
16:984700:GGGC:G	acceptor_gain	1.0000
16:984700:GGGCA:G	acceptor_gain	1.0000
16:982333:C:T	donor_gain	0.9900
16:982343:CG:C	donor_gain	0.9900
16:982344:GG:G	donor_gain	0.9900
16:983833:G:GT	donor_gain	0.9900
16:983957:ACAG:A	donor_loss	0.9900
16:983958:CAGGT:C	donor_loss	0.9900
16:983959:AGGTG:A	donor_loss	0.9900
16:983961:GTGG:G	donor_loss	0.9900
16:983962:T:G	donor_loss	0.9900
16:984692:T:TA	acceptor_gain	0.9900
16:984699:AGG:A	acceptor_gain	0.9900
16:984700:GGG:G	acceptor_gain	0.9900

AlphaMissense

2883 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:982125:T:A	I68N	1.000
16:982125:T:C	I68T	1.000
16:982149:T:A	L76H	1.000
16:982149:T:C	L76P	1.000
16:982163:T:A	W81R	1.000
16:982163:T:C	W81R	1.000
16:982165:G:C	W81C	1.000
16:982165:G:T	W81C	1.000
16:982231:G:C	K103N	1.000
16:982231:G:T	K103N	1.000
16:982232:C:G	R104G	1.000
16:982232:C:T	R104W	1.000
16:982235:C:A	P105T	1.000
16:982235:C:T	P105S	1.000
16:982236:C:A	P105H	1.000
16:982236:C:G	P105R	1.000
16:982236:C:T	P105L	1.000
16:982239:T:C	M106T	1.000
16:982240:G:A	M106I	1.000
16:982240:G:C	M106I	1.000
16:982240:G:T	M106I	1.000
16:982241:A:C	N107H	1.000
16:982241:A:G	N107D	1.000
16:982241:A:T	N107Y	1.000
16:982242:A:T	N107I	1.000
16:982243:C:A	N107K	1.000
16:982243:C:G	N107K	1.000
16:982247:T:A	F109I	1.000
16:982247:T:C	F109L	1.000
16:982247:T:G	F109V	1.000

dbSNP variants (sampled 300 via entrez): RS1000315691 (16:986193 T>C), RS1000414213 (16:986059 T>A), RS1001073975 (16:980847 G>A), RS1001106016 (16:985425 G>A,C,T), RS1001314183 (16:985733 G>C), RS1001344997 (16:985857 T>C), RS1001505475 (16:981010 C>T), RS1002583168 (16:980515 G>A), RS1003108043 (16:981392 C>CG), RS1003434781 (16:984496 A>T), RS1003738760 (16:984208 G>A), RS1003908849 (16:984823 G>A), RS1003913562 (16:982014 A>T), RS1004086724 (16:980241 G>A,T), RS1004672374 (16:987192 C>G)

Disease associations

OMIM: gene MIM:605923 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (2): 46 XY differences of sex development (MONDO:0020040), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): 46,XY difference of sex development (Orphanet:98085)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001198_34	Multiple sclerosis	8.000000e-08
GCST002741_1	Polycystic ovary syndrome	6.000000e-06
GCST007005_8	Logical memory (immediate recall) in normal cognition	3.000000e-07
GCST009597_28	Multiple sclerosis	3.000000e-15
GCST010396_125	Gut microbiota (bacterial taxa, hurdle binary method)	8.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D058490	Disorder of Sex Development, 46,XY	C12.050.351.875.253.096; C12.200.706.316.096; C12.800.316.096; C16.131.939.316.096; C19.391.119.096
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	6
methylmercuric chloride	increases expression, affects cotreatment	3
trichostatin A	affects cotreatment, increases expression	3
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	decreases expression, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Silver	increases expression	2
FR900359	affects phosphorylation	1
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
cupric oxide	increases expression	1
pentanal	increases expression	1
dinophysistoxin 1	increases expression	1
2-palmitoylglycerol	increases 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
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Bortezomib	increases response to substance	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Aldehydes	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Camptothecin	increases methylation	1
Cisplatin	increases expression	1
Copper	affects binding, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice