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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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GBX1
gastrulation brain homeobox 1
Chromosome 7 Β· 7q36.1
NCBI Gene: 2636Ensembl: ENSG00000164900.5HGNC: HGNC:4185UniProt: Q14549
10PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
chromatinDNA-binding transcription factor activity, RNA polymerase II-specificnucleusRNA polymerase II transcription regulatory region sequence-specific DNA bindingneurodegenerative diseasefamilial amyotrophic lateral sclerosisSyndactyly type 2autosomal dominant sensory ataxia 1
✦AI Summary

GBX1 (gastrulation brain homeobox 1) is a DNA-binding transcription factor that functions as a homeodomain protein targeting TAATTA motifs in double-stranded DNA 1. The gene encodes a homeobox protein active in RNA polymerase II-mediated transcriptional regulation [GO annotations]. GBX1 is dynamically expressed during embryonic development, first appearing during gastrulation and subsequently in the central nervous system including rhombomeres 3 and 5, optic vesicles, and the medial ganglionic eminence 2. The protein exhibits preferential expression in germinal vesicle oocytes 3 and participates in epithelial differentiation and transdifferentiation processes, functioning cooperatively with transglutaminase 2 and TGF-beta in retinoic acid-induced epidermal-to-mucosal transdifferentiation 4. Clinically, GBX1 variants have been associated with neurological dysfunction. A de novo GBX1 variant (c.910C>T, p.Gln304*) was identified in a patient with focal epilepsy and developmental delay, representing the first reported human disease association 5. Zebrafish models with gbx1 disruption demonstrated interocular morphological abnormalities and increased susceptibility to epileptiform activity, confirming GBX1's importance in neurological function 5.

Sources cited
1
De novo GBX1 variant associated with focal epilepsy and developmental delay; zebrafish models show morphological abnormalities and epileptiform susceptibility
PMID: 40519143
2
GBX1 expressed during gastrulation and in dynamic pattern in CNS including rhombomeres, optic vesicles, and medial ganglionic eminence
PMID: 12799077
3
GBX1 homeodomain targets TAATTA motifs; DNA binding induces dynamic conformational changes
PMID: 27396829
4
GBX1 cooperates with TG2/Gh and TGF-beta in retinoic acid-induced epidermal-to-mucosal transdifferentiation
PMID: 22252490
5
GBX1 is a homeobox gene preferentially expressed by germinal vesicle oocytes
PMID: 16597639
Disease Associationsβ“˜20
neurodegenerative diseaseOpen Targets
0.24Weak
familial amyotrophic lateral sclerosisOpen Targets
0.06Suggestive
Syndactyly type 2Open Targets
0.06Suggestive
autosomal dominant sensory ataxia 1Open Targets
0.05Suggestive
syndactyly type 5Open Targets
0.05Suggestive
mesoaxial synostotic syndactyly with phalangeal reductionOpen Targets
0.05Suggestive
spondylometaphyseal dysplasia, A4 typeOpen Targets
0.05Suggestive
Charcot-Marie-Tooth disease type 1AOpen Targets
0.05Suggestive
amyotrophic lateral sclerosisOpen Targets
0.05Suggestive
syndactyly type 4Open Targets
0.05Suggestive
Autosomal recessive intermediate Charcot-Marie-Tooth disease type BOpen Targets
0.05Suggestive
Charcot-Marie-Tooth disease recessive intermediate BOpen Targets
0.05Suggestive
Metaphyseal chondrodysplasia, Schmid typeOpen Targets
0.04Suggestive
Schmid metaphyseal chondrodysplasiaOpen Targets
0.04Suggestive
polydactyly of a triphalangeal thumbOpen Targets
0.04Suggestive
brachydactyly type A7Open Targets
0.04Suggestive
Acropectorovertebral dysplasiaOpen Targets
0.04Suggestive
symphalangism with multiple anomalies of hands and feetOpen Targets
0.04Suggestive
spondylometaphyseal dysplasia, Kozlowski typeOpen Targets
0.04Suggestive
brachydactyly type B2Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar β†—
Related Genes
LINGO3Shared pathway100%LINGO4Shared pathway100%LINGO2Shared pathway100%SOHLH1Protein interaction96%LHX8Protein interaction90%LINGO1Shared pathway50%
Tissue Expression6 tissues
Heart
100%
Ovary
0%
Liver
0%
Brain
0%
Lung
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
GBX1LINGO3LINGO4LINGO2SOHLH1LHX8LINGO1
PROTEIN STRUCTURE
Preparing viewer…
PDB2M34 Β· NMR
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.77LoF Tolerant
pLIβ“˜
0.18Tolerant
Observed/Expected LoF0.44 [0.26–0.77]
RankingsWhere GBX1 stands among ~20K protein-coding genes
  • #17,062of 20,598
    Most Researched10
  • #6,221of 17,882
    Most Constrained (LOEUF)0.77
Genes detectedGBX1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
De Novo Variant in GBX1 Gene Associated With Developmental Delay and Focal Epilepsy.
PMID: 40519143
Mol Genet Genomic Med Β· 2025
1.00
2
Cloning and embryonic expression analysis of the mouse Gbx1 gene.
PMID: 12799077
Gene Expr Patterns Β· 2003
0.90
3
Increase in expression of the homeobox gene, GBX1, in retinol-induced epidermal mucous metaplasia.
PMID: 11162634
Biochem Biophys Res Commun Β· 2001
0.80
4
Dynamic Local Polymorphisms in the Gbx1 Homeodomain Induced by DNA Binding.
PMID: 27396829
Structure Β· 2016
0.70
5
cDNA cloning and expression of the human NOBOX gene in oocytes and ovarian follicles.
PMID: 16597639
Mol Hum Reprod Β· 2006
0.60