VSX2 (visual system homeobox 2)

Gene

• Entrez ID: 338917
• Gene name: Visual system homeobox 2
• Gene symbol: VSX2
• Synonyms (NCBI Gene): CHX10, HOX10, MCOP2, MCOPCB3, RET1
• Chromosome: 14
• Chromosome location: 14q24.3
• Summary: This gene encodes a homeobox protein originally described as a retina-specific transcription factor. Mutations in this gene are associated with microphthalmia, cataracts and iris abnormalities. [provided by RefSeq, Oct 2009]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121912543	G>A,C	Pathogenic	Missense variant, coding sequence variant
rs121912545	C>T	Pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs189139917	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs375294678	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, missense variant
rs377107974	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs752313464	G>A	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs755799430	G>A	Pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs869025268	->G	Pathogenic	Coding sequence variant, frameshift variant
rs1555387462	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1566888340	G>A	Pathogenic	Stop gained, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1487958	hsa-miR-1253	CLIP-seq
MIRT1487959	hsa-miR-145	CLIP-seq
MIRT1487960	hsa-miR-1910	CLIP-seq
MIRT1487961	hsa-miR-219-1-3p	CLIP-seq
MIRT1487962	hsa-miR-3135b	CLIP-seq
MIRT1487963	hsa-miR-3148	CLIP-seq
MIRT1487964	hsa-miR-3176	CLIP-seq
MIRT1487965	hsa-miR-3689a-3p	CLIP-seq
MIRT1487966	hsa-miR-3689c	CLIP-seq
MIRT1487967	hsa-miR-3922-3p	CLIP-seq
MIRT1487968	hsa-miR-4259	CLIP-seq
MIRT1487969	hsa-miR-4425	CLIP-seq
MIRT1487970	hsa-miR-4434	CLIP-seq
MIRT1487971	hsa-miR-4516	CLIP-seq
MIRT1487972	hsa-miR-4646-5p	CLIP-seq
MIRT1487973	hsa-miR-4653-3p	CLIP-seq
MIRT1487974	hsa-miR-4682	CLIP-seq
MIRT1487975	hsa-miR-4743	CLIP-seq
MIRT1487976	hsa-miR-4753-5p	CLIP-seq
MIRT1487977	hsa-miR-4755-3p	CLIP-seq
MIRT1487978	hsa-miR-4782-5p	CLIP-seq
MIRT1487979	hsa-miR-571	CLIP-seq
MIRT1487980	hsa-miR-661	CLIP-seq
MIRT2146855	hsa-miR-2467-3p	CLIP-seq
MIRT2146856	hsa-miR-3151	CLIP-seq
MIRT2146857	hsa-miR-485-5p	CLIP-seq
MIRT2146858	hsa-miR-486-3p	CLIP-seq
MIRT2367427	hsa-miR-1237	CLIP-seq
MIRT2367428	hsa-miR-128	CLIP-seq
MIRT2367429	hsa-miR-2861	CLIP-seq
MIRT2367430	hsa-miR-377	CLIP-seq
MIRT2367431	hsa-miR-412	CLIP-seq
MIRT2367432	hsa-miR-4318	CLIP-seq
MIRT2367433	hsa-miR-4446-5p	CLIP-seq
MIRT2367434	hsa-miR-4711-3p	CLIP-seq
MIRT1487964	hsa-miR-3176	CLIP-seq
MIRT1487967	hsa-miR-3922-3p	CLIP-seq
MIRT2463345	hsa-miR-3190	CLIP-seq
MIRT2367430	hsa-miR-377	CLIP-seq
MIRT2367431	hsa-miR-412	CLIP-seq
MIRT2367432	hsa-miR-4318	CLIP-seq
MIRT2367434	hsa-miR-4711-3p	CLIP-seq
MIRT2463346	hsa-miR-671-5p	CLIP-seq
MIRT2463345	hsa-miR-3190	CLIP-seq
MIRT2367430	hsa-miR-377	CLIP-seq
MIRT2367431	hsa-miR-412	CLIP-seq
MIRT2367432	hsa-miR-4318	CLIP-seq
MIRT2367434	hsa-miR-4711-3p	CLIP-seq
MIRT2463346	hsa-miR-671-5p	CLIP-seq
MIRT2660903	hsa-miR-1	CLIP-seq
MIRT2660904	hsa-miR-1321	CLIP-seq
MIRT2660905	hsa-miR-206	CLIP-seq
MIRT2660906	hsa-miR-2392	CLIP-seq
MIRT2146855	hsa-miR-2467-3p	CLIP-seq
MIRT2660907	hsa-miR-3605-5p	CLIP-seq
MIRT2660908	hsa-miR-3673	CLIP-seq
MIRT2660909	hsa-miR-4270	CLIP-seq
MIRT2660910	hsa-miR-4441	CLIP-seq
MIRT2660911	hsa-miR-4694-3p	CLIP-seq
MIRT2660912	hsa-miR-4728-5p	CLIP-seq
MIRT2660913	hsa-miR-4739	CLIP-seq
MIRT2660914	hsa-miR-4756-5p	CLIP-seq
MIRT2660915	hsa-miR-522	CLIP-seq
MIRT2660916	hsa-miR-587	CLIP-seq
MIRT2660917	hsa-miR-613	CLIP-seq
MIRT2660903	hsa-miR-1	CLIP-seq
MIRT2695099	hsa-miR-1293	CLIP-seq
MIRT2660904	hsa-miR-1321	CLIP-seq
MIRT2660905	hsa-miR-206	CLIP-seq
MIRT2660906	hsa-miR-2392	CLIP-seq
MIRT2146855	hsa-miR-2467-3p	CLIP-seq
MIRT2660907	hsa-miR-3605-5p	CLIP-seq
MIRT2660908	hsa-miR-3673	CLIP-seq
MIRT2660909	hsa-miR-4270	CLIP-seq
MIRT2660910	hsa-miR-4441	CLIP-seq
MIRT2695100	hsa-miR-4483	CLIP-seq
MIRT2660911	hsa-miR-4694-3p	CLIP-seq
MIRT2660912	hsa-miR-4728-5p	CLIP-seq
MIRT2660913	hsa-miR-4739	CLIP-seq
MIRT2660914	hsa-miR-4756-5p	CLIP-seq
MIRT2660915	hsa-miR-522	CLIP-seq
MIRT2660916	hsa-miR-587	CLIP-seq
MIRT2660917	hsa-miR-613	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
NEUROG3	Activation	19028584

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IDA	15647262
GO:0000785	Component	Chromatin	ISA
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA	15647262
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IEA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001227	Function	DNA-binding transcription repressor activity, RNA polymerase II-specific	IDA	15647262
GO:0003677	Function	DNA binding	IEA
GO:0005515	Function	Protein binding	IPI	32814053
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0007405	Process	Neuroblast proliferation	IEA
GO:0007406	Process	Negative regulation of neuroblast proliferation	IEA
GO:0007601	Process	Visual perception	IEA
GO:0008283	Process	Cell population proliferation	IEA
GO:0008284	Process	Positive regulation of cell population proliferation	IEA
GO:0021953	Process	Central nervous system neuron differentiation	IEA
GO:0043010	Process	Camera-type eye development	IEA
GO:0045165	Process	Cell fate commitment	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0060040	Process	Retinal bipolar neuron differentiation	IEA
GO:0060042	Process	Retina morphogenesis in camera-type eye	IEA
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IBA
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 142993
• HGNC: 1975
• e!Ensembl: ENSG00000119614

Protein

• UniProt ID: P58304
• Protein name: Visual system homeobox 2 (Ceh-10 homeodomain-containing homolog) (Homeobox protein CHX10)
• Protein function: Acts as a transcriptional regulator through binding to DNA at the consensus sequence 5'-[TC]TAATT[AG][AG]-3' upstream of gene promoters (PubMed:27301076). Plays a significant role in the specification and morphogenesis of the sensory retina (By
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00046	Homeodomain	149 → 205	Homeodomain	Domain
  PF03826	OAR	300 → 318	OAR motif	Motif

• Tissue specificity: TISSUE SPECIFICITY: Abundantly expressed in retinal neuroblasts during eye development and in the inner nuclear layer of the adult retina. Within this layer, expression is stronger in the outer margin where bipolar cells predominate.
• Sequence:

  MTGKAGEALSKPKSETVAKSTSGGAPARCTGFGIQEILGLNKEPPSSHPRAALDGLAPGH
  LLAARSVLSPAGVGGMGLLGPGGLPGFYTQPTFLEVLSDPQSVHLQPLGRASGPLDTSQT
  ASSDSEDVSSSDRKMSKSALNQTKKRKKRRHRTIFTSYQLEELEKAFNEAHYPDVYAREM
  LAMKTELPEDRIQVWFQNRRAKWRKREKCWGRSSVMAEYGLYGAMVRHSIPLPESILKSA
  KDGIMDSCAPWLLGMHKKSLEAAAESGRKPEGERQALPKLDKMEQDERGPDAQAAISQEE
  LRENSIAVLRAKAQEHSTKVLGTVSGPDSLARSTEKPEEEEAMDEDRPAERLSPPQLEDM
  A

• Sequence length: 361

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Anophthalmia	Likely pathogenic; Pathogenic	rs121912545	RCV000786019	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Anophthalmia-microphthalmia syndrome	Pathogenic; Likely pathogenic	rs869025268, rs755799430	RCV000207414 RCV000207355	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Isolated microphthalmia 2	Pathogenic; Likely pathogenic	rs768459071, rs755997898, rs1389175061, rs2139628331, rs2139628604, rs2139645825, rs2139628524, rs2139628344, rs2139645844, rs2139628382, rs1395124261, rs2504956615, rs2504945945, rs2504945051, rs2504948607, rs755799430, rs2504973070, rs869025268, rs2504945525, rs2504973144, rs2477623961, rs2504948671, rs121912543, rs121912545, rs1033708386, rs2139629943, rs752288097, rs1409419238, rs774922468	RCV001915878 RCV001384317 RCV001942909 RCV001925563 RCV001905978 RCV001931412 RCV001910499 RCV002000144 RCV001993138 RCV001879333 RCV001884138 RCV002756871 RCV002835089 RCV002852768 RCV002885006 RCV003026986 RCV003035344 RCV003517148 RCV001378265 RCV003517050 RCV003517658 RCV003630329 RCV003630373 RCV001851882 RCV000015987 RCV000015988 RCV003630776 RCV003831738 RCV003852133 RCV001052936 RCV001206613 RCV001201789	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Microphthalmia	Likely pathogenic; Pathogenic	rs755799430, rs121912545	RCV001828043 RCV000786019	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Microphthalmia, cataracts, and iris abnormalities	Pathogenic; Likely pathogenic	rs121912543	RCV000015985 RCV000015986	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Microphthalmia, isolated, with coloboma 3	Likely pathogenic; Pathogenic	rs1389175061, rs1395124261, rs121912543, rs121912545, rs752288097	RCV005006213 RCV002077342 RCV001330573 RCV000714543 RCV005012495	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Retinitis pigmentosa	Pathogenic	rs1566888340	RCV000678661	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
VSX2-related disorder	Likely pathogenic; Pathogenic	rs121912543	RCV004755737	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
VSX2-related Microphthalmia	Likely pathogenic; Pathogenic	rs755799430, rs121912545	RCV000778906 RCV004586011	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ANOPHTHALMOS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BLINDNESS AND LOW VISION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLOBOMATOUS MICROPHTHALMIA	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL CYSTIC EYEBALL	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CROHN'S DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INFLAMMATORY BOWEL DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Isolated microphthalmia 6	Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMIA AND MENTAL DEFICIENCY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMIA, ISOLATED 2	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMIA, ISOLATED 6	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMIA, ISOLATED, WITH COLOBOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMIA/COLOBOMA 3	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMOS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMOS CO-OCCURRENT WITH CONGENITAL OCULAR COLOBOMA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OCULAR SARCOIDOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ULCERATIVE COLITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Angle Closure Glaucoma	Angle Closure Glaucoma	BEFREE	18648522		★☆☆☆☆ Found in Text Mining only
Angle Closure Glaucoma	Angle Closure Glaucoma	LHGDN	18648522		★☆☆☆☆ Found in Text Mining only
Anophthalmia with pulmonary hypoplasia	Anophthalmia	Pubtator	11826019	Associate	★☆☆☆☆ Found in Text Mining only
Anophthalmos	Syndromic microphthalmia	BEFREE	15257456, 18385794, 19397404, 21203406, 21976963		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anophthalmos	Anophthalmia	Pubtator	16113496, 18385794	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anophthalmos	Syndromic microphthalmia	LHGDN	17661825		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bipolar Disorder	Bipolar disorder	Pubtator	36264558	Associate	★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	BEFREE	15257456		★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colobomatous microphthalmia	Microphthalmia With Coloboma	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal Carcinoma	Colorectal Cancer	BEFREE	21636702		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	21636702	Associate	★☆☆☆☆ Found in Text Mining only
Congenital ocular coloboma (disorder)	Congenital ocular coloboma	BEFREE	15257456, 24859618		★☆☆☆☆ Found in Text Mining only
Congenital ocular coloboma (disorder)	Congenital ocular coloboma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Disorder of eye	Disorder Of Eye	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Eye Abnormalities	Eye abnormalities	Pubtator	31078532	Associate	★☆☆☆☆ Found in Text Mining only
Glaucoma Angle Closure	Angle closure glaucoma	Pubtator	18648522	Associate	★☆☆☆☆ Found in Text Mining only
Isolated microphthalmia-anophthalmia-coloboma	Isolated Microphthalmia-Anophthalmia-Coloboma	Orphanet			★☆☆☆☆ Found in Text Mining only
Lens Subluxation	Lens Subluxation	BEFREE	24001013		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	25278453		★☆☆☆☆ Found in Text Mining only
Microphthalmia, Cataracts, and Iris Abnormalities	Microphthalmia, Cataracts, And Iris Abnormalities	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
MICROPHTHALMIA, ISOLATED 1	Microphthalmia	ORPHANET_DG	10932181		★☆☆☆☆ Found in Text Mining only
MICROPHTHALMIA, ISOLATED 2	Microphthalmia	UNIPROT_DG	15257456, 21976963		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMIA, ISOLATED 2	Microphthalmia	GENOMICS_ENGLAND_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMIA, ISOLATED 2	Microphthalmia	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMIA, ISOLATED 2	Microphthalmia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microphthalmia, Isolated, with Coloboma 3	Microphthalmia With Coloboma	GENOMICS_ENGLAND_DG	10932181		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Microphthalmia, Isolated, with Coloboma 3	Microphthalmia With Coloboma	UNIPROT_DG	10932181, 15257456, 17919464, 24033328, 27301076		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Microphthalmia, Isolated, with Coloboma 3	Microphthalmia With Coloboma	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Microphthalmos	Microphthalmos	BEFREE	10932181, 15257456, 17167404, 18385794, 18648522, 19397404, 20414678, 21203406, 21976963, 24001013, 31078532		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microphthalmos	Microphthalmos	Pubtator	16113496, 17167404, 18385794, 18648522, 31078532	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microphthalmos	Microphthalmos	CLINVAR_DG	26893459		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microphthalmos	Microphthalmos	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microphthalmos co-occurrent with congenital ocular coloboma	Microphthalmos Co-Occurrent With Congenital Ocular Coloboma	BEFREE	21203406		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microphthalmos, Autosomal Recessive	Microphthalmos	ORPHANET_DG	10932181		★☆☆☆☆ Found in Text Mining only
Nanophthalmos 1	Nanophthalmos	Pubtator	17167404	Associate	★☆☆☆☆ Found in Text Mining only
Night blindness congenital stationary	Night blindness, congenital stationary	Pubtator	36264558	Associate	★☆☆☆☆ Found in Text Mining only
Primary angle-closure glaucoma	Angle closure glaucoma	BEFREE	18648522		★☆☆☆☆ Found in Text Mining only
Retinal Diseases	Retinal detachment	Pubtator	10329014	Associate	★☆☆☆☆ Found in Text Mining only
Retinal Dystrophies	Retinal Dystrophy	BEFREE	20414678		★☆☆☆☆ Found in Text Mining only
Retinitis Pigmentosa	Retinitis Pigmentosa	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)