GATA3

Chr 10AD

GATA binding protein 3

Also known as: HDR, HDRS

NCBI Gene: 2625ENSG00000107485UniProt: P23771OMIM: 131320

The GATA3 transcription factor binds to specific DNA sequences to regulate T-cell development and differentiation, particularly in Th2 immune responses, and also functions in endothelial cell biology. Loss-of-function mutations cause autosomal dominant hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR syndrome). The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the underlying disease mechanism.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.391 OMIM phenotype
Clinical Summary— GATA3
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Gene-Disease Validity (ClinGen)
hypoparathyroidism-deafness-renal disease syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.90) — some intolerance to loss-of-function variants.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.899
Z-score 3.27
OE 0.12 (0.05–0.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.91Z-score
OE missense 0.67 (0.59–0.76)
181 obs / 269.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.05–0.39)
0≤0.351.4
Missense OE0.67 (0.59–0.76)
0≤0.61.4
Synonymous OE1.33
0≤1.21.6
LoF obs/exp: 2 / 16.2Missense obs/exp: 181 / 269.3Syn Z: -2.91
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveGATA3-related hypoparathyroidism, sensorineural deafness, and renal diseaseLOFAD
DN
0.4686th %ile
GOF
0.2398th %ile
LOF
0.89top 5%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · 1 literature citation · LOEUF 0.39
DN1 literature citation
GOF1 literature citation

Literature Evidence

DNNovel dominant-negative mutant of GATA3 in HDR syndrome.PMID:21120445
GOFIn this study, we identify differential functional consequences of mutation types in GATA3. We present evidence that the most common mutation type results in a protein with elongated C-terminus that displays effects consistent with gain-of-function activity in a cell line model.PMID:27588951
LOFGATA3 haplo-insufficiency causes human HDR syndromePMID:10935639

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

GATA3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
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