SOX2

SRY-box transcription factor 2, the group of SRY-box transcription factors

Basic information

Region (hg38): 3:181711925-181714436

Links

ENSG00000181449 ∙ NCBI:6657 ∙ OMIM:184429 ∙ HGNC:11195 ∙ Uniprot:P48431 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• anophthalmia/microphthalmia-esophageal atresia syndrome (Moderate), mode of inheritance: AD
• anophthalmia/microphthalmia-esophageal atresia syndrome (Definitive), mode of inheritance: AD
• anophthalmia/microphthalmia-esophageal atresia syndrome (Strong), mode of inheritance: AD
• anophthalmia/microphthalmia-esophageal atresia syndrome (Limited), mode of inheritance: AD
• septooptic dysplasia (Supportive), mode of inheritance: AD
• isolated anophthalmia-microphthalmia syndrome (Supportive), mode of inheritance: AD
• anophthalmia/microphthalmia-esophageal atresia syndrome (Supportive), mode of inheritance: AD
• anophthalmia/microphthalmia-esophageal atresia syndrome (Definitive), mode of inheritance: AD
• anophthalmia/microphthalmia-esophageal atresia syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microphthalmia, syndromic 3	AD	Endocrine	Individuals may demonstrate endocrine anomalies such as growth hormone deficiency, and early recognition and treatment may be beneficial	Craniofacial; Dental; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	10564870; 12002146; 12612584; 12749061; 15346919; 16145681; 15389708; 15812812; 16283891; 16470798; 16932809; 16543359; 16892407; 19254784; 17219395; 18831064; 19921648; 20301477; 20301552; 20803647
Individuals may demonstrate endocrine anomalies such as growth hormone deficiency, and early recognition and treatment may be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SOX2 gene.

• Anophthalmia/microphthalmia-esophageal atresia syndrome (31 variants)
• not provided (16 variants)
• Anophthalmia (2 variants)
• SOX2-related disorder (1 variants)
• Septo-optic dysplasia sequence (1 variants)
• Inborn genetic diseases (1 variants)
• Microphthalmia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SOX2 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			4	29	4	37
missense	2	8	45	5	4	64
nonsense	12	2	1			15
start loss						0
frameshift	28	4				32
inframe indel	1		2			3
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				3	6	9
Total	43	14	52	37	14

Highest pathogenic variant AF is 0.00000659

Variants in SOX2

This is a list of pathogenic ClinVar variants found in the SOX2 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-181712324-C-T			Benign (Mar 03, 2015)
3-181712330-C-T		not specified	Benign (May 26, 2015)
3-181712336-GGCCGGGCCCGCGCACAGCGCCCGCATGTACAACATGATGGAGACGGAGCTGAAGCC-G		Anophthalmia/microphthalmia-esophageal atresia syndrome	Pathogenic (-)
3-181712341-G-T			Likely benign (Apr 26, 2018)
3-181712350-A-C			Likely benign (Mar 23, 2018)
3-181712362-T-TG		Anophthalmia/microphthalmia-esophageal atresia syndrome	Pathogenic (Dec 19, 2019)
3-181712376-G-T		Anophthalmia/microphthalmia-esophageal atresia syndrome	Pathogenic (-)
3-181712380-C-T		Congenital aniridia	Uncertain significance (Apr 17, 2020)
3-181712381-G-C		Anophthalmia/microphthalmia-esophageal atresia syndrome	Uncertain significance (Oct 05, 2023)
3-181712382-G-T		Anophthalmia/microphthalmia-esophageal atresia syndrome	Likely pathogenic (Nov 26, 2020)
3-181712384-GC-G		Anophthalmia/microphthalmia-esophageal atresia syndrome	Pathogenic (Dec 22, 2022)
3-181712393-G-T		Anophthalmia/microphthalmia-esophageal atresia syndrome • SOX2-related disorder	Likely benign (Jun 18, 2017)
3-181712399-C-A		Anophthalmia/microphthalmia-esophageal atresia syndrome	Likely benign (Dec 18, 2022)
3-181712402-G-T			Likely benign (Feb 05, 2021)
3-181712405-G-A		Anophthalmia/microphthalmia-esophageal atresia syndrome	Likely benign (Jan 06, 2024)
3-181712411-T-C			Likely benign (Jul 31, 2018)
3-181712412-TC-AA		Anophthalmia/microphthalmia-esophageal atresia syndrome	Conflicting classifications of pathogenicity (Jan 02, 2024)
3-181712413-C-A		Anophthalmia/microphthalmia-esophageal atresia syndrome	Pathogenic (Dec 19, 2019)
3-181712413-CG-C		Anophthalmia/microphthalmia-esophageal atresia syndrome	Pathogenic (-)
3-181712413-C-CG		Anophthalmia/microphthalmia-esophageal atresia syndrome	Pathogenic (Sep 03, 2021)
3-181712414-G-C			Conflicting classifications of pathogenicity (Jul 21, 2018)
3-181712413-C-CGG		Anophthalmia/microphthalmia-esophageal atresia syndrome	Pathogenic (Jul 01, 2009)
3-181712416-G-T		Inborn genetic diseases	Uncertain significance (Oct 12, 2021)
3-181712416-GG-TT			Uncertain significance (Nov 30, 2023)
3-181712417-GGGCGGCGGCGGCAACTCCACCGC-G		Anophthalmia/microphthalmia-esophageal atresia syndrome	Pathogenic (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SOX2	protein_coding	protein_coding	ENST00000325404	1	2508

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.707	0.290	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.12	107	189	0.566	0.00000899	2067
Missense in Polyphen		14	53.076	0.26377		600
Synonymous	-1.06	97	84.6	1.15	0.00000421	633
Loss of Function	2.36	1	8.34	0.120	3.66e-7	91

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)	0.00	0.00
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 forms a trimeric complex with OCT4 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206 (By similarity). Critical for early embryogenesis and for embryonic stem cell pluripotency. May function as a switch in neuronal development. Downstream SRRT target that mediates the promotion of neural stem cell self-renewal (By similarity). Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation (By similarity). {ECO:0000250, ECO:0000269|PubMed:18035408}.
• Disease: DISEASE: Microphthalmia, syndromic, 3 (MCOPS3) [MIM:206900]: A disease characterized by the rare association of malformations including uni- or bilateral anophthalmia or microphthalmia, and esophageal atresia with trachoesophageal fistula. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. {ECO:0000269|PubMed:12612584, ECO:0000269|PubMed:24033328}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Cell Differentiation - Index expanded;Cardiac Progenitor Differentiation;Transcriptional regulation of pluripotent stem cells;Endoderm Differentiation;Dopaminergic Neurogenesis;Mesodermal Commitment Pathway;Ectoderm Differentiation;let-7 inhibition of ES cell reprogramming;Preimplantation Embryo;Wnt Signaling Pathway and Pluripotency;Interleukin-4 and 13 signaling;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Developmental Biology;Signaling by WNT;Signal Transduction;POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation;Deactivation of the beta-catenin transactivating complex;POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation;Transcriptional regulation of pluripotent stem cells;TCF dependent signaling in response to WNT (Consensus)

Recessive Scores

• pRec: 0.586

Intolerance Scores

• rvis_EVS: -0.12
• rvis_percentile_EVS: 44.54

Haploinsufficiency Scores

• pHI: 0.897
• hipred: Y
• hipred_score: 0.856
• ghis: 0.617

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.960

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sox2
• Phenotype: skeleton phenotype; immune system phenotype; vision/eye phenotype; hearing/vestibular/ear 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; neoplasm; pigmentation phenotype; reproductive 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); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; muscle phenotype; endocrine/exocrine gland phenotype; taste/olfaction 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

Zebrafish Information Network

• Gene name: sox2
• Affected structure: auditory receptor cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;osteoblast differentiation;eye development;endodermal cell fate specification;chromatin organization;regulation of transcription, DNA-templated;cell cycle arrest;central nervous system development;response to wounding;regulation of gene expression;cytokine-mediated signaling pathway;glial cell fate commitment;pituitary gland development;adenohypophysis development;positive regulation of cell-cell adhesion;cell differentiation;neuron differentiation;forebrain development;somatic stem cell population maintenance;tissue regeneration;regulation of cysteine-type endopeptidase activity involved in apoptotic process;positive regulation of MAPK cascade;cell fate commitment;positive regulation of cell differentiation;negative regulation of neuron differentiation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;inner ear development;negative regulation of epithelial cell proliferation;response to growth factor;negative regulation of canonical Wnt signaling pathway;neuronal stem cell population maintenance
• Cellular component: nucleus;nucleoplasm;transcription factor complex;cytoplasm;cytosol;nuclear transcription factor complex
• Molecular function: transcription regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;miRNA binding;sequence-specific DNA binding;transcription regulatory region DNA binding