GATA3

Chr 10

GATA binding protein 3

Also known as: HDR, HDRS

NCBI Gene: 2625 ENSG00000107485 UniProt: P23771

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.

GeneReviews 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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHypoparathyroidism, sensorineural deafness, and renal disease

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · hypoparathyroidism-deafness-renal disease syndrome · AD · ClinGen 2019

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

837

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.39

LOEUF

LOF

Mechanism· G2P

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GeneReview available — GATA3

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in GATA3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

545 rare PASS variants

Rare truncating (LoF)

1 in 14,000

19 rare PASS variants

Rare synonymous (reference)

1 in 140

347 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GATA3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 13,000
South Asian	~43k	1 in 120	≈ 1 in 41,000
Remaining (unassigned)	~30k	1 in 120	≈ 1 in 15,000
European (Finnish)	~27k	1 in 300	1 in 1,300
Admixed American	~22k	1 in 220	≈ 1 in 22,000
African / African American	~21k	1 in 190	none seen
East Asian	~20k	1 in 160	none seen
Ashkenazi Jewish	~13k	1 in 600	none seen
Middle Eastern	~2,884	≈ 1 in 960	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓