VAX1
protein-codingventral anterior homeobox 1, the group of NKL subclass homeoboxes and pseudogenes
Gene summary
This gene encodes a homeo-domain containing protein from a class of homeobox transcription factors which are conserved in vertebrates. Genes of this family are involved in the regulation of body development and morphogenesis. The most conserved genes, called HOX genes are found in special gene clusters. This gene belongs to the VAX subfamily and lies in the vicinity of the EMX homeobox gene family. Another member of VAX family is located on chromosome 2. The encoded protein may play an important role in the development of anterior ventral forebrain and visual system. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013734
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0013734
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0013734
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0013734
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Neurologic; 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to VAX1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001112704.2. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 15 | 3 | 20 | ||
| missense | 1 | 49 | 1 | 51 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 3 | 4 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 1 | 55 | 16 | 3 | 76 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001106175.1 | 3 | MANE Select | |
| Ensembl | ENSP00000358207.4 | 3 | MANE Select | |
| RefSeq | NP_954582.1 | 4 | Standard | |
| Ensembl | ENSP00000277905.2 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of transcription by RNA polymerase II
- neuron migration
- negative regulation of neuroblast proliferation
- axon guidance
- brain development
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- chromatin DNA binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369206
- Coding exons
- 3
- Length
- 9781
- Individuals with no LoFs
- 124206
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 124207
- p
- 0.00000403
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.869 | 115 | 144 | 0.796 | 0.00000771 | 2069 |
| Missense (PolyPhen) | 2 | 5.7168 | 0.34984 | 111 | ||
| Synonymous | 0.104 | 70 | 71.1 | 0.984 | 0.00000392 | 772 |
| Loss of Function | 2.51 | 1 | 9.22 | 0.108 | 4.56e-7 | 111 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000089 | 0.0000089 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription factor that may function in dorsoventral specification of the forebrain. Required for axon guidance and major tract formation in the developing forebrain. May contribute to the differentiation of the neuroretina, pigmented epithelium and optic stalk (By similarity). {ECO:0000250}.;
- Disease
- DISEASE: Microphthalmia, syndromic, 11 (MCOPS11) [MIM:614402]: A rare clinical entity including as main characteristics microphthalmia and small optic nerves, cleft lip and palate, absence of corpus callosum, hippocampal malformations, and absence of the pineal gland. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. {ECO:0000269|PubMed:22095910}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- LoFtool
- 0.151
- RVIS EVS
- -0.27
- RVIS percentile EVS
- 33.97
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.424
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |