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7 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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STOX2
storkhead box 2
Chromosome 4 · 4q35.1
NCBI Gene: 56977Ensembl: ENSG00000173320.13HGNC: HGNC:25450UniProt: Q9P2F5
22PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
maternal placenta developmentembryo development ending in birth or egg hatchingnucleuscytoplasmopen-angle glaucomamathematical abilitydyshidrosisvitamin deficiency disorder
✦AI Summary

STOX2 (storkhead box 2) is a transcriptional regulatory factor that functions as a DNA-binding transcription factor involved in placental and embryonic development 1. As a member of the storkhead box family, STOX2 acts as a master control gene regulating trophoblast differentiation pathways 2. The protein contains a highly conserved C-terminal domain critical for function, with alternative splicing patterns regulated by a long non-coding RNA within intron 3 2. STOX2 functions as a novel SMAD2/4 cofactor in TGF-β signaling within embryonic stem cells 3. Disease relevance: STOX2 is implicated in pre-eclampsia with fetal growth restriction, showing significantly lower expression in affected decidual tissue 4. The gene also plays critical roles in malignancy progression. In oral squamous cell carcinoma, STOX2 upregulation correlates with nodal metastasis and poor outcome, promoting cell growth, invasion, and chemotherapy resistance 1. In hydatidiform moles, miR-30a-mediated STOX2 downregulation activates ERK, AKT, and P38 signaling, driving excessive trophoblast proliferation 5. Additionally, STOX2 expression is regulated by lysyl-oxidase family genes in breast cancer, with LOX-dependent STOX2 upregulation promoting tumor progression 6.

Sources cited
1
STOX2 is a transcriptional factor; upregulation correlates with nodal metastasis and poor outcome in oral squamous cell carcinoma; promotes cell growth, invasion, suppresses apoptosis, and enhances chemotherapy resistance
PMID: 27050375
2
STOX2 is a master control gene regulating trophoblast differentiation; contains a conserved C-terminal domain; alternative splicing is regulated by a long non-coding RNA within intron 3
PMID: 27555360
3
STOX2 is a novel primary target of TGF-β signaling and acts as a SMAD2/4 cofactor in human embryonic stem cells
PMID: 33339109
4
STOX2 shows significantly lower expression in decidual tissue from pregnancies complicated by both pre-eclampsia and fetal growth restriction
PMID: 20643876
5
miR-30a targets STOX2; STOX2 downregulation activates ERK, AKT, and P38 signaling pathways promoting trophoblast proliferation and metastasis in hydatidiform moles
PMID: 35246136
6
STOX2 is regulated by lysyl-oxidase genes; LOX-dependent STOX2 expression promotes tumor progression in breast cancer
PMID: 36232621
Disease Associationsⓘ20
open-angle glaucomaOpen Targets
0.43Moderate
mathematical abilityOpen Targets
0.41Moderate
dyshidrosisOpen Targets
0.28Weak
vitamin deficiency disorderOpen Targets
0.27Weak
intracerebral hemorrhageOpen Targets
0.26Weak
Conductive hearing impairmentOpen Targets
0.25Weak
ovarian neoplasmOpen Targets
0.23Weak
type 1 diabetes mellitusOpen Targets
0.16Weak
obesityOpen Targets
0.12Weak
oral squamous cell carcinomaOpen Targets
0.08Suggestive
synovium disorderOpen Targets
0.06Suggestive
hemoglobin D diseaseOpen Targets
0.05Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.05Suggestive
dominant beta-thalassemiaOpen Targets
0.04Suggestive
intestinal diseaseOpen Targets
0.04Suggestive
Familial drusenOpen Targets
0.04Suggestive
hemoglobin H diseaseOpen Targets
0.04Suggestive
hemoglobin E diseaseOpen Targets
0.04Suggestive
Hemoglobin C - beta-thalassemiaOpen Targets
0.04Suggestive
hemoglobin C-beta-thalassemia syndromeOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MFRPShared pathway100%RAI2Shared pathway50%PAX1Shared pathway33%FOXI1Shared pathway33%SCELShared pathway20%UBR3Shared pathway17%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
21%
Heart
15%
Liver
6%
Ovary
6%
Lung
3%
Gene Interaction Network
Click a node to explore
STOX2MFRPRAI2PAX1FOXI1SCELUBR3
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9P2F5
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.57Moderately Constrained
pLIⓘ
0.26Tolerant
Observed/Expected LoF0.41 [0.30–0.57]
RankingsWhere STOX2 stands among ~20K protein-coding genes
  • #13,756of 20,598
    Most Researched22
  • #3,795of 17,882
    Most Constrained (LOEUF)0.57 · top quartile
Genes detectedSTOX2
Sources retrieved7 papers
Response time—
📄 Sources
7▼
1
Storkhead box 2 and melanoma inhibitory activity promote oral squamous cell carcinoma progression.
PMID: 27050375
Oncotarget · 2016
1.00
2
miR-30a targets STOX2 to increase cell proliferation and metastasis in hydatidiform moles via ERK, AKT, and P38 signaling pathways.
PMID: 35246136
Cancer Cell Int · 2022
0.86
3
MicroRNA Regulation of Bone Marrow Mesenchymal Stem Cell Chondrogenesis: Toward Articular Cartilage.
PMID: 34328786
Tissue Eng Part A · 2022
0.71
4
Knock-Out of the Five Lysyl-Oxidase Family Genes Enables Identification of Lysyl-Oxidase Pro-Enzyme Regulated Genes.
PMID: 36232621
Int J Mol Sci · 2022
0.57
5
Noncoding RNA-regulated gain-of-function of STOX2 in Finnish pre-eclamptic families.
PMID: 27555360
Sci Rep · 2016
0.43