GBX2

Chr 2

gastrulation brain homeobox 2

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.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
7
Pubs (1 yr)
63
P/LP submissions
0%
P/LP missense
0.56
LOEUF
LOF
Mechanism· predicted
Clinical SummaryGBX2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.71) — some intolerance to loss-of-function variants.
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ClinVar Variants
63 unique Pathogenic / Likely Pathogenic· 56 VUS of 125 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.56LOEUF
pLI 0.713
Z-score 2.37
OE 0.12 (0.040.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.40Z-score
OE missense 0.71 (0.620.82)
134 obs / 188.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.040.56)
00.351.4
Missense OE0.71 (0.620.82)
00.61.4
Synonymous OE0.78
01.21.6
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

125 submitted variants in ClinVar

Classification Summary

Pathogenic62
Likely Pathogenic1
VUS56
Likely Benign3
Benign2
62
Pathogenic
1
Likely Pathogenic
56
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
62
0
62
Likely Pathogenic
0
0
1
0
1
VUS
0
48
8
0
56
Likely Benign
0
0
2
1
3
Benign
0
1
0
1
2
Total049732124

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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