GATA3

Chr 10AD

GATA binding protein 3

Also known as: HDR, HDRS

NCBI Gene: 2625 ENSG00000107485 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a protein which belongs to the GATA family of transcription factors. The protein contains two GATA-type zinc fingers and is an important regulator of T-cell development and plays an important role in endothelial cell biology. Defects in this gene are the cause of hypoparathyroidism with sensorineural deafness and renal dysplasia. [provided by RefSeq, Nov 2009]

OMIM ResearchGenerating clinical summary…

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 OE?0.12 (0.05–0.39)

0≤0.351.4

Missense OE?0.67 (0.59–0.76)

0≤0.61.4

Synonymous OE?1.33

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

This gene — mechanism propensity

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 · ClinGen HI: Sufficient evidence for dosage pathogenicity

DN1 literature citation

GOF1 literature citation

Literature Evidence

DNNovel dominant-negative mutant of GATA3 in HDR syndrome.1

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.2

LOFGATA3 haplo-insufficiency causes human HDR syndrome3

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

References

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.

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

HER 2 Negative Breast Cancer

A Multicenter, Single-Arm, Phase II Exploratory Study of Eribulin in Combination With Anlotinib for HER2-Negative Recurrent/Metastatic Breast Cancer Previously Treated With Antibody-Drug Conjugates

RECRUITING

NCT07520760Phase PHASE2Sun Yat-sen UniversityStarted 2026-04-01

Eribulin in Combination with Anlotinib

Breast Cancer

Investigation of the Prognostic Value of Patterns of Genomic Alterations or Protein Expression in Patients With Operated Early Breast Cancer

ACTIVE NOT RECRUITING

NCT07630558Hellenic Cooperative Oncology GroupStarted 1997-01-31

Transplantation InfectionKidney Diseases

Molecular Biological and Moleculargenetic Monitoring of Therapy After Kidney Transplantation

RECRUITING

NCT01515605Odense University HospitalStarted 2011-01-01

Clinical Literature