VSX1

visual system homeobox 1, the group of PRD class homeoboxes and pseudogenes

Basic information

Region (hg38): 20:25070885-25082141

Previous symbols: [ "PPCD" ]

Links

ENSG00000100987 ∙ NCBI:30813 ∙ OMIM:605020 ∙ HGNC:12723 ∙ Uniprot:Q9NZR4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• keratoconus 1 (Limited), mode of inheritance: AD
• posterior polymorphous corneal dystrophy (Supportive), mode of inheritance: AD
• craniofacial anomalies and anterior segment dysgenesis syndrome (Limited), mode of inheritance: AD
• keratoconus 1 (Limited), mode of inheritance: AD
• posterior polymorphous corneal dystrophy 1 (Limited), mode of inheritance: Unknown
• keratoconus 1 (Limited), mode of inheritance: Unknown
• craniofacial anomalies and anterior segment dysgenesis syndrome (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Craniofacial anomalies and anterior segment dysgenesis syndrome; Keratoconus 1; Corneal dystrophy, posterior polymorphous	AD	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	Craniofacial; Ophthalmologic	11978762; 15051220; 15623752; 16735990; 18216574; 18626569; 19763142; 19956409; 20664914; 21365019; 21976959; 26045363

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VSX1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VSX1 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			3	11	6	20
missense			39	5	6	50
nonsense			2			2
start loss				1		1
frameshift				1		1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	2	3
non coding			13	3	8	24
Total	0	0	57	21	20

Variants in VSX1

This is a list of pathogenic ClinVar variants found in the VSX1 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-25071957-G-A			Uncertain significance (-)
20-25075441-A-G		Polymorphous corneal dystrophy	Uncertain significance (Jan 13, 2018)
20-25075512-G-A		Polymorphous corneal dystrophy	Uncertain significance (Jan 12, 2018)
20-25075516-C-T		Polymorphous corneal dystrophy	Benign (Jan 13, 2018)
20-25075517-G-T		Polymorphous corneal dystrophy	Benign (Jan 13, 2018)
20-25075651-C-T		Polymorphous corneal dystrophy	Uncertain significance (Jan 13, 2018)
20-25075755-A-G		Polymorphous corneal dystrophy	Uncertain significance (Jun 14, 2016)
20-25075765-T-C		Polymorphous corneal dystrophy	Benign (Jan 13, 2018)
20-25075807-TC-T		Polymorphous corneal dystrophy	Benign (Jun 14, 2016)
20-25075845-A-G		Polymorphous corneal dystrophy	Uncertain significance (Jan 12, 2018)
20-25075865-A-C		Polymorphous corneal dystrophy	Uncertain significance (Jan 12, 2018)
20-25076038-C-T		Polymorphous corneal dystrophy	Uncertain significance (Jun 14, 2016)
20-25076061-C-A		Polymorphous corneal dystrophy	Benign (Jan 12, 2018)
20-25076062-C-T		Polymorphous corneal dystrophy	Benign (Jan 12, 2018)
20-25076092-C-T		Polymorphous corneal dystrophy	Uncertain significance (Jan 13, 2018)
20-25076102-C-T		Polymorphous corneal dystrophy	Uncertain significance (Jan 13, 2018)
20-25076149-T-C		Polymorphous corneal dystrophy	Uncertain significance (Jan 12, 2018)
20-25076157-G-A		Polymorphous corneal dystrophy	Benign (Jan 13, 2018)
20-25076172-A-G		Polymorphous corneal dystrophy	Uncertain significance (Jan 13, 2018)
20-25076173-G-C		Polymorphous corneal dystrophy	Uncertain significance (Jan 13, 2018)
20-25076197-C-A		Polymorphous corneal dystrophy	Uncertain significance (Apr 27, 2017)
20-25076258-G-T		Polymorphous corneal dystrophy	Likely benign (Apr 27, 2017)
20-25076292-C-T		Inborn genetic diseases	Uncertain significance (Feb 12, 2024)
20-25076326-C-A		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
20-25076362-G-A			Uncertain significance (Mar 11, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VSX1	protein_coding	protein_coding	ENST00000376709	5	11476

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0359	0.932	125739	0	7	125746	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.482	181	200	0.904	0.00000988	2281
Missense in Polyphen		49	63.666	0.76964		723
Synonymous	-0.917	97	86.2	1.13	0.00000426	788
Loss of Function	1.85	4	10.5	0.382	5.35e-7	108

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to the 37-bp core of the locus control region (LCR) of the red/green visual pigment gene cluster. May regulate the activity of the LCR and the cone opsin genes at earlier stages of development.
• Disease: DISEASE: Craniofacial anomalies and anterior segment dysgenesis syndrome (CAASDS) [MIM:614195]: A disorder with extremely variable expressivity. Clinical features include wide interpupillary distance, abnormal corneal endothelium, unusual pinnae, partially to completely empty sella turcica, posterior fossa cyst, anterior encephalocele, and/or hydrocephalus. {ECO:0000269|PubMed:15051220}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.137

Haploinsufficiency Scores

• pHI: 0.115
• hipred: N
• hipred_score: 0.209
• ghis: 0.428

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.349

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vsx1
• Phenotype: 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)

Zebrafish Information Network

• Gene name: vsx1
• Affected structure: ventricular system
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;visual perception;neuron maturation;neuron development;response to stimulus;retinal bipolar neuron differentiation
• Cellular component: cellular_component;nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;chromatin binding;DNA-binding transcription factor activity;sequence-specific DNA binding;transcription regulatory region DNA binding