GeneBe

VSX1

protein-coding

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

Gene summary

The protein encoded by this gene contains a paired-like homeodomain and binds to the core of the locus control region of the red/green visual pigment gene cluster. The encoded protein may regulate expression of the cone opsin genes early in development. Mutations in this gene can cause posterior polymorphous corneal dystrophy and keratoconus. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

Previous symbols:
  • PPCD

MANE transcript

NM_014588.6

Inheritance

AD

ClinVar variants

U:94B:41

Top phenotype

Craniofacial anomalies and anterior segment dysgenesis syndrome; Keratoconus 1; Corneal dystrophy, posterior polymorphous

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr20:25,070,885-25,082,141

External References & Databases

Ensembl (ENSG00000100987)NCBI Gene (30813)OMIM (605020)HGNC:12723GenCCUniProt (Q9NZR4)AlphaFoldClinVar (VSX1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~11.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

posterior polymorphous corneal dystrophySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020364

Submitter: Orphanet

keratoconus 1LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0007851

Submitter: Labcorp Genetics (formerly Invitae)

keratoconus 1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0007851

Submitter: G2P

craniofacial anomalies and anterior segment dysgenesis syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013618

Submitter: G2P

posterior polymorphous corneal dystrophy 1LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0007378

Submitter: Labcorp Genetics (formerly Invitae)

keratoconus 1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0007851

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

keratoconus 1MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0007851

Submitter: PanelApp Australia

craniofacial anomalies and anterior segment dysgenesis syndromeLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0013618

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Craniofacial anomalies and anterior segment dysgenesis syndrome; Keratoconus 1; Corneal dystrophy, posterior polymorphousAD

Manifestation: Craniofacial; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 11978762; 15051220; 15623752; 16735990; 18216574; 18626569; 19763142; 19956409; 20664914; 21365019; 21976959; 26045363Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VSX1 variants in ClinVar

10 Conditions Cataloged
Inborn genetic diseasesTotal: 65
not providedTotal: 64
Posterior polymorphous corneal dystrophyTotal: 34
VSX1-related disorderTotal: 10
Keratoconus 1Total: 9
Craniofacial anomalies and anterior segment dysgenesis syndromeTotal: 7
not specifiedTotal: 4
Long QT syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014588.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
3
clinvar
17
clinvar
5
clinvar
 25
missense
85
clinvar
12
clinvar
5
clinvar
 102
nonsense
3
clinvar
 3
start loss
1
clinvar
 1
frameshift
2
clinvar
1
clinvar
 3
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total00943110135
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_014588.6RefSeqNP_055403.25MANE Select
ENST00000376709.9EnsemblENSP00000365899.35MANE Select
NM_001256271.2RefSeqNP_001243200.14Standard
NM_001256272.2RefSeqNP_001243201.15Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
vsx1Danio rerio

Structure: ventricular system

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • regulation of transcription, DNA-templated
  • regulation of transcription by RNA polymerase II
  • visual perception
  • neuron maturation
  • neuron development

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

Cellular Component

  • cellular_component
  • nucleus

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000376709
Coding exons
5
Length
11476
Individuals with no LoFs
125739
Homozygous LoFs
0
Heterozygous LoFs
7
Defined
125746
p
0.0000278
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.4821812000.9040.000009882281
Missense (PolyPhen)4963.6660.76964723
Synonymous-0.9179786.21.130.00000426788
Loss of Function1.85410.50.3825.35e-7108

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000350.000035rare
South Asian0.0000980.000098rare
Other00.0absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.349

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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