Details for: VAX1

Gene ID: 11023

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: VAX1

Ensembl ID: ENSG00000148704

Description: ventral anterior homeobox 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • pvalb GABAergic cortical interneuron CL4023018
    CSI 18.24
    rCSI 22.7%
    PRS 99.95
  • sst GABAergic cortical interneuron CL4023017
    CSI 17.78
    rCSI 22.92%
    PRS 99.97
  • neural progenitor cell CL0011020
    CSI 6.79
    rCSI 29.89%
    PRS 98.63

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Ventral anterior homeobox 1 ([VAX1](/details-gene/11023)) is a homeobox-containing, protein-coding gene that functions as a DNA-binding transcription factor. Located on chromosome 10, it plays a critical role in the development of the central nervous system. Its function is particularly associated with processes such as [axon guidance](/details-ontology/GO:0007411), [brain development](/details-ontology/GO:0007420), and the development of the eye. Expression data reveals that [VAX1](/details-gene/11023) is a highly specific marker for distinct neuronal populations, showing significant expression in [pvalb GABAergic cortical interneurons](/details-cell/CL4023018) and [sst GABAergic cortical interneurons](/details-cell/CL4023017), as well as in [neural progenitor cells](/details-cell/CL0011020). Clinically, mutations in [VAX1](/details-gene/11023) have been linked to severe congenital anomalies, including microphthalmia, agenesis of the corpus callosum, and orofacial clefting, underscoring its essential role in embryonic development ([Link](https://doi.org/10.1002/humu.21658)). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [VAX1](/details-gene/11023) highlights its specialized function within the central nervous system. The gene exhibits highly significant expression in specific subtypes of inhibitory neurons, including [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 18.24) and [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 17.78). This suggests that [VAX1](/details-gene/11023) is not merely a general neuronal marker but is integral to the identity and function of these particular interneuron classes. Its notable significance in [neural progenitor cells](/details-cell/CL0011020) (CSI: 6.79) is consistent with its established role during neurogenesis, likely regulating the differentiation and fate decisions of these precursor cells as they mature into specialized neurons. The data collectively points to [VAX1](/details-gene/11023) as a key transcriptional regulator governing the establishment and maintenance of specific GABAergic neuron lineages in the cortex. ## Pathways and Molecular Function [VAX1](/details-gene/11023) encodes a transcription factor that exerts its function primarily within the [nucleus](/details-ontology/GO:0005634), where it binds to [chromatin](/details-ontology/GO:0000785). Its molecular activity is characterized as a [DNA-binding transcription repressor activity, rna polymerase ii-specific](/details-ontology/GO:0001227), indicating that it primarily functions by downregulating the expression of its target genes. This regulatory activity is central to its involvement in a range of critical biological processes essential for neurodevelopment. Key annotated functions include orchestrating [central nervous system development](/details-ontology/GO:0007417), guiding neuronal migration and connectivity through [axon guidance](/details-ontology/GO:0007411), and contributing to [camera-type eye development](/details-ontology/GO:0043010). Furthermore, [VAX1](/details-gene/11023) is implicated in controlling the balance between cell division and differentiation, as evidenced by its roles in [negative regulation of neuroblast proliferation](/details-ontology/GO:0007406) and promoting [neuron differentiation](/details-ontology/GO:0030182) and [astrocyte differentiation](/details-ontology/GO:0048708). This suite of functions is consistent with its high expression in [neural progenitor cells](/details-cell/CL0011020) and mature interneurons, where it likely directs cell fate decisions and sculpts neural circuits. ## Research Directions The established link between [VAX1](/details-gene/11023) mutations and severe congenital disorders such as corpus callosum agenesis ([Link](https://doi.org/10.1002/humu.21658)) provides a strong foundation for further investigation into its precise molecular mechanisms during human development. Based on the available data, several testable hypotheses can be proposed: 1. **VAX1 as a Fate Determinant for Cortical Interneurons:** Given its high and specific expression in [pvalb](/details-cell/CL4023018) and [sst-positive interneurons](/details-cell/CL4023017), it is hypothesized that [VAX1](/details-gene/11023) acts as a terminal selector gene that specifies these interneuron subtypes from a common progenitor pool. Its loss-of-function during development would likely result in a skewed ratio of interneuron populations or a failure of these cells to acquire their mature identity. 2. **Role in Axon Midline Crossing:** The association with corpus callosum agenesis suggests a critical role in commissural axon pathfinding. It is hypothesized that [VAX1](/details-gene/11023) directly represses the expression of axon-repellent factors or activates adhesion molecules within callosal projection neurons, thereby permitting their axons to cross the cortical midline. To test the first hypothesis regarding interneuron fate specification, a compelling experimental approach would be to utilize a human cortical organoid model. CRISPR-Cas9 could be used to generate a [VAX1](/details-gene/11023) knockout in human pluripotent stem cells. These cells, alongside isogenic wild-type controls, would be differentiated into cortical organoids. Single-cell RNA sequencing at various time points during organoid development would reveal a high-resolution map of cell fate trajectories, allowing for direct assessment of whether the loss of [VAX1](/details-gene/11023) prevents the emergence or maturation of PVALB+ and SST+ interneuron lineages. Given that [VAX1](/details-gene/11023) is a fundamental developmental transcription factor whose absence leads to severe congenital defects, its potential as a direct therapeutic target for these conditions is limited. Postnatal modulation is unlikely to reverse structural abnormalities established in utero. Therefore, its primary clinical utility lies in the realm of diagnostics and genetic counseling. However, a deeper understanding of the pathways it regulates could inform strategies for cell-based therapies aiming to generate specific neuronal subtypes for transplantation in other neurological disorders.

Genular Protein ID: 1997723843

Symbol: VAX1_HUMAN

Name: Ventral anterior homeobox 1

UniProtKB Accession Codes:

Q5SQQ9 B1AVW5 Q6ZSX0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 2 GO 21 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 2 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 22095910

Title: VAX1 mutation associated with microphthalmia, corpus callosum agenesis, and orofacial clefting: The first description of a VAX1 phenotype in humans.

PubMed ID: 22095910

DOI: 10.1002/humu.21658

Sequence Information:

  • Length: 334
  • Mass: 34713
  • Checksum: 927FCADCFE937C12
  • Sequence:
    • MFGKPDKMDV RCHSDAEAAR VSKNAHKESR ESKGAEGNLP AAFLKEPQGA FSASGAAEDC 
NKSKSNSAAD PDYCRRILVR DAKGSIREII LPKGLDLDRP KRTRTSFTAE QLYRLEMEFQ 
RCQYVVGRER TELARQLNLS ETQVKVWFQN RRTKQKKDQG KDSELRSVVS ETAATCSVLR 
LLEQGRLLSP PGLPALLPPC ATGALGSALR GPSLPALGAG AAAGSAAAAA AAAPGPAGAA 
SPHPPAVGGA PGPGPAGPGG LHAGAPAAGH SLFSLPVPSL LGSVASRLSS APLTMAGSLA 
GNLQELSARY LSSSAFEPYS RTNNKEGAEK KALD