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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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VSX2
visual system homeobox 2
Chromosome 14 Β· 14q24.3
NCBI Gene: 338917Ensembl: ENSG00000119614.3HGNC: HGNC:1975UniProt: P58304
40PubMed Papers
23Diseases
0Drugs
53Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
RNA polymerase II transcription regulatory region sequence-specific DNA bindingDNA-binding transcription repressor activity, RNA polymerase II-specificprotein bindingsequence-specific double-stranded DNA bindingIsolated anophthalmia - microphthalmiamicrophthalmia, isolated, with colobomaEDICT syndromemicrophthalmia
✦AI Summary

VSX2 is a transcriptional regulator that binds DNA at the consensus sequence 5'-[TC]TAATT[AG][AG]-3' 1 and serves as a master regulator of retinal development. In the retina, VSX2 marks multipotent retinal progenitor cells (RPCs) throughout development 2 and is essential for eye organogenesis, with mutations causing congenital microphthalmia 3. VSX2 functions through its homeodomain and CVC domain to maintain high-affinity DNA binding required for retinal progenitor identity and proliferation 3. During retinal differentiation, VSX2-positive cells progress from RPCs to bipolar cells and MΓΌller glia 4. The gene operates through stage- and cell-type-specific super-enhancer modules that regulate its complex expression pattern 5. Dysregulation of VSX2 enhancer modules causes distinct retinal defects: one module deletion leads to microphthalmia through reduced RPC proliferation, while another deletion specifically disrupts bipolar neuron development without affecting overall retinal architecture 6. Beyond retina, VSX2 marks V2a interneurons in spinal cord, where these cells demonstrate therapeutic potential for spinal cord injury repair 7. VSX2 mutations in humans cause microphthalmia and coloboma diseases, establishing direct links between transcriptional dysfunction and congenital ocular malformations.

Sources cited
1
VSX2 binds DNA at specific consensus sequence and maintains retinal neural identity through Wnt signaling regulation
PMID: 27301076
2
VSX2 labels all multipotent retinal progenitor cells and indicates neurogenic competence in retinal cultures
PMID: 26292211
3
VSX2 homeodomain and CVC domain are required for high-affinity DNA binding essential for eye organogenesis and retinal progenitor identity
PMID: 23028343
4
VSX2-eGFP+ cells mark early stage RPCs and late stage bipolar cells in human retinal organoids with dynamic transcriptional profiles
PMID: 41152974
5
VSX2 super-enhancer modules regulate developmental stage- and cell-type-specific gene expression; module deletion causes microphthalmia or bipolar neuron loss
PMID: 37905144
6
VSX2 super-enhancer modules are evolutionarily conserved and human sequences rescue mouse microphthalmia; module deletion disrupts organoid size and bipolar development
PMID: 38994775
7
VSX2-expressing V2a spinal interneurons form functional synapses in injured spinal cord and promote therapeutic recovery
PMID: 38260390
Disease Associationsβ“˜23
Isolated anophthalmia - microphthalmiaOpen Targets
0.76Strong
microphthalmia, isolated, with colobomaOpen Targets
0.72Strong
EDICT syndromeOpen Targets
0.55Moderate
microphthalmiaOpen Targets
0.54Moderate
anophthalmia-microphthalmia syndromeOpen Targets
0.43Moderate
retinitis pigmentosaOpen Targets
0.38Weak
isolated microphthalmiaOpen Targets
0.37Weak
retinal detachmentOpen Targets
0.37Weak
AnophthalmiaOpen Targets
0.34Weak
musculoskeletal system diseaseOpen Targets
0.31Weak
respiratory tract infectious disorderOpen Targets
0.25Weak
genetic disorderOpen Targets
0.19Weak
nanophthalmiaOpen Targets
0.10Suggestive
retinopathyOpen Targets
0.09Suggestive
choroidal dystrophy, central areolar, 1Open Targets
0.08Suggestive
X-linked retinal dysplasiaOpen Targets
0.08Suggestive
microphthalmia, isolated, with coloboma 10Open Targets
0.08Suggestive
congenital primary aphakiaOpen Targets
0.08Suggestive
microphthalmia, isolated, with coloboma 7Open Targets
0.08Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.07Suggestive
Microphthalmia with cataracts and iris abnormalitiesUniProt
Microphthalmia, isolated, 2UniProt
Microphthalmia/Coloboma 3UniProt
Pathogenic Variants53
NM_182894.3(VSX2):c.598C>T (p.Arg200Ter)Pathogenic
Isolated microphthalmia 2|Microphthalmia
β˜…β˜…β˜†β˜†2025β†’ Residue 200
NM_182894.3(VSX2):c.267del (p.Gln90fs)Pathogenic
Isolated microphthalmia 2|Microphthalmia, isolated, with coloboma 3;Isolated microphthalmia 2|Microphthalmia
β˜…β˜…β˜†β˜†2025β†’ Residue 90
NM_182894.3(VSX2):c.584G>A (p.Trp195Ter)Pathogenic
Isolated microphthalmia 2|Microphthalmia
β˜…β˜…β˜†β˜†2025β†’ Residue 195
NM_182894.3(VSX2):c.599G>A (p.Arg200Gln)Pathogenic
Microphthalmia, cataracts, and iris abnormalities|Isolated microphthalmia 2|Microphthalmia
β˜…β˜…β˜†β˜†2025β†’ Residue 200
NM_182894.3(VSX2):c.589C>T (p.Gln197Ter)Pathogenic
Isolated microphthalmia 2|Microphthalmia
β˜…β˜…β˜†β˜†2025β†’ Residue 197
NM_182894.3(VSX2):c.679C>T (p.Arg227Trp)Pathogenic
Isolated microphthalmia 2|Microphthalmia, isolated, with coloboma 3|Anophthalmia;Microphthalmia|VSX2-related Microphthalmia|Isolated microphthalmia 2;Microphthalmia, isolated, with coloboma 3
β˜…β˜…β˜†β˜†2025β†’ Residue 227
NM_182894.3(VSX2):c.695del (p.Leu232fs)Likely pathogenic
Isolated microphthalmia 2;Microphthalmia, isolated, with coloboma 3|Microphthalmia
β˜…β˜…β˜†β˜†2024β†’ Residue 232
NM_182894.3(VSX2):c.371-1G>APathogenic
Isolated microphthalmia 2|Microphthalmia, isolated, with coloboma 3|Microphthalmia
β˜…β˜…β˜†β˜†2024
NM_182894.3(VSX2):c.87C>A (p.Cys29Ter)Pathogenic
Isolated microphthalmia 2|Microphthalmia, isolated, with coloboma 3;Isolated microphthalmia 2
β˜…β˜…β˜†β˜†2024β†’ Residue 29
NM_182894.3(VSX2):c.667G>A (p.Gly223Arg)Pathogenic
Anophthalmia-microphthalmia syndrome|VSX2-related Microphthalmia|Isolated microphthalmia 2|Microphthalmia
β˜…β˜…β˜†β˜†2024β†’ Residue 223
NM_182894.3(VSX2):c.71dup (p.Ala25fs)Pathogenic
Anophthalmia-microphthalmia syndrome|Isolated microphthalmia 2
β˜…β˜…β˜†β˜†2023β†’ Residue 25
NM_182894.3(VSX2):c.599G>C (p.Arg200Pro)Pathogenic
Microphthalmia, cataracts, and iris abnormalities|Isolated microphthalmia 2|VSX2-related disorder|not provided|Microphthalmia, isolated, with coloboma 3
β˜…β˜…β˜†β˜†2023β†’ Residue 200
NM_182894.3(VSX2):c.972_973del (p.Ser325fs)Likely pathogenic
Microphthalmia
β˜…β˜†β˜†β˜†2026β†’ Residue 325
NM_182894.3(VSX2):c.438del (p.Lys147fs)Pathogenic
Isolated microphthalmia 2
β˜…β˜†β˜†β˜†2025β†’ Residue 147
NM_182894.3(VSX2):c.1086G>C (p.Ter362Tyr)Likely pathogenic
Microphthalmia
β˜…β˜†β˜†β˜†2025β†’ Residue 362
NM_182894.3(VSX2):c.760+1delLikely pathogenic
Microphthalmia
β˜…β˜†β˜†β˜†2025
NM_182894.3(VSX2):c.371-2A>CPathogenic
Microphthalmia
β˜…β˜†β˜†β˜†2025
NM_182894.3(VSX2):c.870dup (p.Asp291fs)Likely pathogenic
Microphthalmia
β˜…β˜†β˜†β˜†2025β†’ Residue 291
NM_182894.3(VSX2):c.1059del (p.Pro354fs)Likely pathogenic
Microphthalmia
β˜…β˜†β˜†β˜†2025β†’ Residue 354
NM_182894.3(VSX2):c.316C>T (p.Gln106Ter)Pathogenic
Microphthalmia, isolated, with coloboma 3
β˜…β˜†β˜†β˜†2025β†’ Residue 106
View on ClinVar β†—
Related Genes
SIX3Protein interaction87%ATOH7Protein interaction82%NXNL1Protein interaction82%MFRPProtein interaction79%RCVRNProtein interaction78%RHOProtein interaction78%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
50%
Liver
0%
Ovary
0%
Heart
0%
Lung
0%
Gene Interaction Network
Click a node to explore
VSX2SIX3ATOH7NXNL1MFRPRCVRNRHO
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P58304
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.35LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.98 [0.73–1.35]
RankingsWhere VSX2 stands among ~20K protein-coding genes
  • #10,262of 20,598
    Most Researched40
  • #1,281of 5,498
    Most Pathogenic Variants53 Β· top quartile
  • #14,117of 17,882
    Most Constrained (LOEUF)1.35
Genes detectedVSX2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Dynamic molecular and cellular characteristics of VSX2-positive retinal progenitor cells in human retinal organoids.
PMID: 41152974
Stem Cell Res Ther Β· 2025
1.00
2
VSX2 and ASCL1 Are Indicators of Neurogenic Competence in Human Retinal Progenitor Cultures.
PMID: 26292211
PLoS One Β· 2015
0.90
3
Evolutionary conservation of VSX2 super-enhancer modules in retinal development.
PMID: 38994775
Development Β· 2024
0.80
4
Retinal pigment epithelium extracellular vesicles are potent inducers of age-related macular degeneration disease phenotype in the outer retina.
PMID: 36544284
J Extracell Vesicles Β· 2022
0.70
5
PMID: 35831950
0.60