GeneBe

SOX2

protein-coding

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

Gene summary

This intronless gene encodes a member of the SRY-related HMG-box (SOX) family of transcription factors involved in the regulation of embryonic development and in the determination of cell fate. The product of this gene is required for stem-cell maintenance in the central nervous system, and also regulates gene expression in the stomach. Mutations in this gene have been associated with optic nerve hypoplasia and with syndromic microphthalmia, a severe form of structural eye malformation. This gene lies within an intron of another gene called SOX2 overlapping transcript (SOX2OT). [provided by RefSeq, Jul 2008]

MANE transcript

NM_003106.4

Inheritance

AD

ClinVar variants

P:112U:113B:62

Top phenotype

Microphthalmia, syndromic 3

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr3:181,711,925-181,714,436

External References & Databases

Ensembl (ENSG00000181449)NCBI Gene (6657)OMIM (184429)HGNC:11195GenCCUniProt (P48431)AlphaFoldClinVar (SOX2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~2.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

septooptic dysplasiaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008428

Submitter: Orphanet

anophthalmia/microphthalmia-esophageal atresia syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008799

Submitter: Orphanet

anophthalmia/microphthalmia-esophageal atresia syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008799

Submitter: Illumina

anophthalmia/microphthalmia-esophageal atresia syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0008799

Submitter: Ambry Genetics

anophthalmia/microphthalmia-esophageal atresia syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008799

Submitter: PanelApp Australia

anophthalmia/microphthalmia-esophageal atresia syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008799

Submitter: Labcorp Genetics (formerly Invitae)

anophthalmia/microphthalmia-esophageal atresia syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008799

Submitter: G2P

Clinical Genomic Database (CGD)

Microphthalmia, syndromic 3AD

Manifestation: Craniofacial; Dental; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: Endocrine

Rationale: Individuals may demonstrate endocrine anomalies such as growth hormone deficiency, and early recognition and treatment may be beneficial

Comments: Individuals may demonstrate endocrine anomalies such as growth hormone deficiency, and early recognition and treatment may be beneficial

Refs: 10564870; 12002146; 12612584; 12749061; 15346919; 16145681; 15389708; 15812812; 16283891; 16470798; 16932809; 16543359; 16892407; 19254784; 17219395; 18831064; 19921648; 20301477; 20301552; 20803647Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SOX2 variants in ClinVar

17 Conditions Cataloged
Anophthalmia/microphthalmia-esophageal atresia syndromeTotal: 174
not providedTotal: 109
Inborn genetic diseasesTotal: 35
not specifiedTotal: 22
SOX2-related disorderTotal: 21
OPTIC NERVE HYPOPLASIA AND ABNORMALITIES OF THE CENTRAL NERVOUS SYSTEMTotal: 2
AnophthalmiaTotal: 2
Chorioretinal colobomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003106.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
12
clinvar
36
clinvar
4
clinvar
 52
missense
9
clinvar
13
clinvar
99
clinvar
18
clinvar
4
clinvar
 143
nonsense
19
clinvar
11
clinvar
2
clinvar
 32
start loss
1
clinvar
 1
frameshift
47
clinvar
12
clinvar
 59
splice donor/acceptor (+/-2bp)
0
Total7636113548287

Highest pathogenic variant AF is 0.000016151296

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_003106.4RefSeqNP_003097.11MANE Select
ENST00000325404.3EnsemblENSP00000323588.11MANE Select

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
sox2Danio rerio

Structure: auditory receptor cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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

Biological Process

  • negative regulation of transcription by RNA polymerase II
  • osteoblast differentiation
  • eye development
  • endodermal cell fate specification
  • chromatin organization

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

Cellular Component

  • nucleus
  • nucleoplasm
  • transcription factor complex
  • cytoplasm
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000325404
Coding exons
1
Length
2508
Individuals with no LoFs
0
Homozygous LoFs
0
Heterozygous LoFs
0
Defined
0
p
0.00
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.121071890.5660.000008992067
Missense (PolyPhen)1453.0760.26377600
Synonymous-1.069784.61.150.00000421633
Loss of Function2.3618.340.1203.66e-791

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.586

Intolerance Scores

RVIS EVS
-0.12
RVIS percentile EVS
44.54

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.960

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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