SOX2

Chr 3AD

SRY-box transcription factor 2

Also known as: ANOP3, MCOPS3

NCBI Gene: 6657 ENSG00000181449 UniProt: P48431 OMIM: 184429

SOX2 encodes a transcription factor that is critical for embryonic stem cell pluripotency and maintains neural stem cells in an undifferentiated state by suppressing neuronal differentiation. Mutations cause autosomal dominant microphthalmia with severe structural eye malformations and optic nerve hypoplasia, often accompanied by central nervous system abnormalities. The gene is highly constrained against loss-of-function variation (LOEUF 0.569), reflecting its essential role in early development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Microphthalmia, syndromic 3MIM #206900

Optic nerve hypoplasia and abnormalities of the central nervous systemMIM #206900

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.57

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.57LOEUF

pLI 0.707

Z-score 2.36

OE 0.12 (0.04–0.57)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.12Z-score

OE missense 0.57 (0.48–0.66)

107 obs / 189.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.12 (0.04–0.57)

0≤0.351.4

Missense OE?0.57 (0.48–0.66)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 1 / 8.3Missense obs/exp: 107 / 189.1Syn Z: -1.06

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SOX2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Fistula Repair

Endoscopic Injection of Autologous, Activated and Emulsified Fat in Chronic Fistulas of the Gastrointestinal Tract and Pelvic Organs

RECRUITING

NCT06930079Fondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-03-20

Systemic Sclerosis (SSc)

Tissue Modeling in Systemic Sclerosis Using Induced Pluripotent Stem Cells (iPSCs)

NOT YET RECRUITING

NCT07650565Phase NAUniversity Hospital, MontpellierStarted 2026-09

Blood Sample Collection

Open Angle Glaucoma (OAG)NAION( Non-arteritic Anterior Ischemic Optic Neuropathy)

Evaluating ER-100 for Safety in People With Glaucoma or Non-Arteritic Anterior Ischemic Optic Neuropathy (Optic Nerve Conditions)

RECRUITING

NCT07290244Phase PHASE1Life Biosciences Inc.Started 2026-03-02

ER-100 epigenetic therapy

Infertility, MaleGene AbnormalitySterility, Male

Spermatogonial Differentiation Via Testicular Organoid

RECRUITING

NCT06841861Phase PHASE1, PHASE2CellARTs Inc.Started 2024-03-28

Stem cellGenetic ScreeningGenetic Reprogramming

Lung Non-Small Cell CarcinomaStage IV Lung Cancer AJCC v8

A Multiple Antigen Vaccine (STEMVAC) for the Treatment of Patients With Stage IV Non-Small Cell Lung Cancer

RECRUITING

NCT05242965Phase PHASE2University of WashingtonStarted 2023-03-24

CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA VaccineSargramostimComputed Tomography

Prostate Cancer

GU-01: Glycyrrhizin in Prostate Cancer

RECRUITING

NCT06378346Phase PHASE2University of Illinois at ChicagoStarted 2024-07-25

ObservationGlycyrrhizin - 75 mgGlycyrrhizin - 150 mg

Anatomic Stage IV Breast Cancer AJCC v8Metastatic HER2-Negative Breast CarcinomaMetastatic Hormone Receptor-Positive Breast Carcinoma

A Vaccine (STEMVAC) With Standard Endocrine-Based Therapy or Chemotherapy for the Treatment of Metastatic Hormone Receptor Positive, HER2 Negative Breast Cancer

RECRUITING

NCT07112053Phase PHASE2University of WashingtonStarted 2025-11-17

CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA VaccineCapecitabineComputed Tomography

Anatomic Stage I Breast Cancer AJCC v8Anatomic Stage II Breast Cancer AJCC v8Anatomic Stage III Breast Cancer AJCC v8

A Vaccine (STEMVAC) for Improving Survival in Patients With Triple-Negative Breast Cancer and Moderate or Extensive Residual Cancer Burden

NOT YET RECRUITING

NCT07721259Phase PHASE2University of WashingtonStarted 2026-09-30

CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA VaccineRecombinant Granulocyte-Macrophage Colony-Stimulating FactorBiospecimen Collection

Clinical Literature

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