SOX2

Chr 3

SRY-box transcription factor 2

Also known as: ANOP3, MCOPS3

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]

ResearchGenerating clinical summary…
LOFmechanismLOEUF 0.57
Clinical SummarySOX2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.71) — some intolerance to loss-of-function variants.
💊
Clinical Trials
7 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.57LOEUF
pLI 0.707
Z-score 2.36
OE 0.12 (0.040.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
2.12Z-score
OE missense 0.57 (0.480.66)
107 obs / 189.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.12 (0.040.57)
00.351.4
Missense OE?0.57 (0.480.66)
00.61.4
Synonymous OE?1.15
01.21.6
LoF obs/exp: 1 / 8.3Missense obs/exp: 107 / 189.1Syn Z: -1.06
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSOX2-related microphthalmia syndromicLOFAD

This gene — mechanism propensity

DN
0.5280th %ile
GOF
0.3491th %ile
LOF
0.83top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFSOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

  1. 1.PMID 17522144

ClinVar Variant Classifications

0 submitted variants in 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Infertility, MaleGene AbnormalitySterility, Male

Spermatogonial Differentiation Via Testicular Organoid

RECRUITING
NCT06841861Phase PHASE1, PHASE2CellARTs Inc.Started 2024-03-28
Stem cellGenetic ScreeningGenetic Reprogramming
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
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
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
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

ACTIVE NOT 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