GBX2
protein-codinggastrulation brain homeobox 2, the group of HOXL subclass homeoboxes
Gene summary
Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of nervous system development and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including branching involved in blood vessel morphogenesis; nervous system development; and neural crest cell migration. Predicted to be located in chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GBX2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001485.4. 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 | 1 | 1 | 2 | |||
| missense | 48 | 1 | 49 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 48 | 1 | 2 | 51 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001476.2 | 2 | MANE Select | |
| Ensembl | ENSP00000302251.4 | 2 | MANE Select | |
| RefSeq | NP_001288616.1 | 3 | Standard | |
| Ensembl | ENSP00000448747.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| gbx2 | Danio rerio | Structure: rhombomere 4 Quality: apoptotic abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neural Crest Differentiation
- Dopaminergic Neurogenesis
Biological Process
- branching involved in blood vessel morphogenesis
- neural crest cell migration
- nervous system development
- axon guidance
- cerebellum development
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- RNA polymerase II core promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000306318
- Coding exons
- 2
- Length
- 3134
- Individuals with no LoFs
- 125660
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125663
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.40 | 134 | 188 | 0.712 | 0.00000961 | 2221 |
| Missense (PolyPhen) | 46 | 75.857 | 0.6064 | 865 | ||
| Synonymous | 1.62 | 67 | 86.1 | 0.778 | 0.00000448 | 731 |
| Loss of Function | 2.37 | 1 | 8.43 | 0.119 | 3.73e-7 | 98 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May act as a transcription factor for cell pluripotency and differentiation in the embryo.;
Recessive Scores
- pRec
- 0.238
Intolerance Scores
- LoFtool
- 0.0466
- RVIS EVS
- -0.23
- RVIS percentile EVS
- 36.86
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.576
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |