GBX2

Chr 2

gastrulation brain homeobox 2

NCBI Gene: 2637ENSG00000168505UniProt: P52951OMIM: 601135

This transcription factor regulates nervous system development and embryonic cell differentiation through sequence-specific DNA binding. Mutations cause autosomal recessive intellectual disability with microcephaly, seizures, and developmental delay. The gene is moderately constrained against loss-of-function variants, and the associated phenotypes primarily affect the nervous system during early development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.56
Clinical Summary— GBX2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.71) — some intolerance to loss-of-function variants.
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.56LOEUF
pLI 0.713
Z-score 2.37
OE 0.12 (0.04–0.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.40Z-score
OE missense 0.71 (0.62–0.82)
134 obs / 188.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.04–0.56)
0≤0.351.4
Missense OE0.71 (0.62–0.82)
0≤0.61.4
Synonymous OE0.78
0≤1.21.6
LoF obs/exp: 1 / 8.4Missense obs/exp: 134 / 188.2Syn Z: 1.62
DN
0.4785th %ile
GOF
0.3391th %ile
LOF
0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

GBX2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Oncogenic GBX2 promotes the malignant behaviors of bladder cancer cells by binding to the ITGA5 promoter and activating its transcription.
Xiong Y et al.·Funct Integr Genomics
2022
Signatures of Adverse Pathological Features, Androgen Insensitivity and Metastatic Potential in Prostate Cancer.
Tolkach Y et al.·Anticancer Res
2015
De Novo Variant in GBX1 Gene Associated With Developmental Delay and Focal Epilepsy.
Zhang B et al.·Mol Genet Genomic Med
2025
Upregulation of the pathogenic transcription factor SPI1/PU.1 in tuberous sclerosis complex and focal cortical dysplasia by oxidative stress.
Zimmer TS et al.·Brain Pathol
2021
[Diagnosis of a case of 2q37 deletion syndrome by whole exome sequencing combined with whole genome low-coverage sequencing method].
Lin H et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2020
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients