VSX2

visual system homeobox 2, the group of PRD class homeoboxes and pseudogenes

Basic information

Region (hg38): 14:74239448-74262738

Previous symbols: [ "HOX10", "CHX10" ]

Links

ENSG00000119614 ∙ NCBI:338917 ∙ OMIM:142993 ∙ HGNC:1975 ∙ Uniprot:P58304 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• isolated anophthalmia-microphthalmia syndrome (Supportive), mode of inheritance: AD
• microphthalmia, isolated, with coloboma (Supportive), mode of inheritance: AD
• microphthalmia (Strong), mode of inheritance: AR
• microphthalmia, isolated, with coloboma 3 (Strong), mode of inheritance: AR
• microphthalmia, isolated, with coloboma 3 (Definitive), mode of inheritance: AR
• isolated microphthalmia 2 (Definitive), mode of inheritance: AR
• microphthalmia, isolated, with coloboma 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microphthalmia, isolated 2; Microphthalmia/coloboma 3	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	3378363; 10932181; 15257456; 17661825; 18648522

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VSX2 gene.

• Isolated microphthalmia 2 (27 variants)
• Microphthalmia, cataracts, and iris abnormalities (1 variants)
• Microphthalmia, isolated, with coloboma 3 (1 variants)
• Anophthalmia-microphthalmia syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VSX2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	182	1	184
missense	2	2	46	1	1	52
nonsense	7					7
start loss						0
frameshift	17	1				18
inframe indel			1		1	2
splice donor/acceptor (+/-2bp)	1	2				3
splice region			3	10		13
non coding			33	76	34	143
Total	27	5	81	259	37

Highest pathogenic variant AF is 0.0000131

Variants in VSX2

This is a list of pathogenic ClinVar variants found in the VSX2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-74239494-G-C		Microphthalmia, isolated, with coloboma 3 • Isolated microphthalmia 2	Uncertain significance (Jan 12, 2018)
14-74239508-G-A		Isolated microphthalmia 2 • Microphthalmia, isolated, with coloboma 3	Uncertain significance (Jan 13, 2018)
14-74239513-T-TG		Isolated microphthalmia 6 • VSX2-related Microphthalmia	Uncertain significance (Jun 14, 2016)
14-74239516-G-C		Microphthalmia, isolated, with coloboma 3 • Isolated microphthalmia 2	Likely benign (Jan 13, 2018)
14-74239564-GA-G		Isolated microphthalmia 2	Pathogenic (Aug 19, 2023)
14-74239567-G-A		Isolated microphthalmia 2	Likely benign (Apr 24, 2023)
14-74239567-G-C		Isolated microphthalmia 2	Likely benign (Aug 19, 2023)
14-74239569-G-A		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)
14-74239575-CA-C		Isolated microphthalmia 2	Pathogenic (Aug 08, 2022)
14-74239579-G-A		Isolated microphthalmia 2	Likely benign (Nov 10, 2023)
14-74239585-G-T		Isolated microphthalmia 2	Likely benign (Jul 17, 2023)
14-74239603-C-A		Isolated microphthalmia 2	Likely benign (Jul 06, 2022)
14-74239609-A-T		Isolated microphthalmia 2	Likely benign (Dec 06, 2020)
14-74239610-G-GTA		Isolated microphthalmia 2	Pathogenic (Feb 03, 2021)
14-74239612-G-A		Isolated microphthalmia 2	Likely benign (May 11, 2021)
14-74239619-AG-A		Isolated microphthalmia 2	Pathogenic (Sep 25, 2021)
14-74239626-C-CG		Anophthalmia-microphthalmia syndrome • Isolated microphthalmia 2	Pathogenic (Jul 31, 2023)
14-74239627-G-C		Isolated microphthalmia 2	Likely benign (Jan 14, 2024)
14-74239630-G-A		Isolated microphthalmia 2	Likely benign (Sep 10, 2023)
14-74239633-C-T		Isolated microphthalmia 2	Likely benign (Oct 19, 2023)
14-74239639-G-A		Isolated microphthalmia 2	Likely benign (Jan 18, 2023)
14-74239639-G-T		Isolated microphthalmia 2	Likely benign (Jul 29, 2023)
14-74239643-AG-A		Isolated microphthalmia 2	Pathogenic (Aug 02, 2021)
14-74239645-G-A		Isolated microphthalmia 2 • VSX2-related disorder	Likely benign (Jan 27, 2023)
14-74239648-C-A		Isolated microphthalmia 2	Pathogenic (Oct 29, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VSX2	protein_coding	protein_coding	ENST00000261980	5	23267

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000165	0.891	125731	0	11	125742	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.561	201	225	0.895	0.0000131	2288
Missense in Polyphen		63	75.633	0.83297		776
Synonymous	-1.13	116	102	1.14	0.00000644	722
Loss of Function	1.46	8	13.8	0.578	6.60e-7	152

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000580	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000632	0.0000615
Middle Eastern	0.0000580	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a significant role in the specification and morphogenesis of the sensory retina. May also participate in the development of the cells of the inner nuclear layer, particularly bipolar cells (By similarity). {ECO:0000250}.
• Disease: DISEASE: Microphthalmia with cataracts and iris abnormalities (MCOPCTI) [MIM:610092]: A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, cataract and other abnormalities like cataract may also be present. {ECO:0000269|PubMed:10932181}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Microphthalmia, isolated, with coloboma, 3 (MCOPCB3) [MIM:610092]: A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). {ECO:0000269|PubMed:15257456, ECO:0000269|PubMed:24033328}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.240

Intolerance Scores

• loftool: 0.164
• rvis_EVS: -0.29
• rvis_percentile_EVS: 32.94

Haploinsufficiency Scores

• pHI: 0.887
• hipred: Y
• hipred_score: 0.542
• ghis: 0.395

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.870

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Vsx2
• Phenotype: pigmentation phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: vsx2
• Affected structure: retinal bipolar neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;multicellular organism development;visual perception;response to stimulus
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;sequence-specific DNA binding