GATA4

Chr 8AD

GATA binding protein 4

Also known as: ASD2, TACHD, TOF, VSD1

NCBI Gene: 2626 ENSG00000136574 UniProt: P43694 OMIM: 600576

This transcription factor binds to GATA DNA motifs and activates cardiac-specific gene expression during heart development, while also being required for normal testicular development. Mutations cause autosomal dominant congenital heart defects including atrial septal defects, ventricular septal defects, tetralogy of Fallot, and atrioventricular septal defects, with some patients also having testicular anomalies. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.53), and cardiac defects are typically present from birth.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the GATA family of zinc-finger transcription factors. Members of this family recognize the GATA motif which is present in the promoters of many genes. This protein is thought to regulate genes involved in embryogenesis and in myocardial differentiation and function, and is necessary for normal testicular development. Mutations in this gene have been associated with cardiac septal defects. Additionally, alterations in gene expression have been associated with several cancer types. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Testicular anomalies with or without congenital heart diseaseMIM #615542

Atrial septal defect 2MIM #607941

Atrioventricular septal defect 4MIM #614430

Tetralogy of FallotMIM #187500

Ventricular septal defect 1MIM #614429

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · GATA4-related congenital heart disease with or without pancreatic hypoplasia or diabetes · AD · ClinGen 2026

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

267

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

LOF

Mechanism· G2P

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GeneReview available — GATA4

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in GATA4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 90

705 rare PASS variants

Rare truncating (LoF)

1 in 5,800

33 rare PASS variants

Rare synonymous (reference)

1 in 74

396 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GATA4. 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 140	1 in 5,700
South Asian	~43k	1 in 96	1 in 3,500
Remaining (unassigned)	~30k	1 in 100	1 in 910
European (Finnish)	~27k	1 in 410	≈ 1 in 9,200
Admixed American	~22k	1 in 130	≈ 1 in 5,600
African / African American	~21k	1 in 81	1 in 2,000
East Asian	~20k	1 in 65	none seen
Ashkenazi Jewish	~13k	1 in 110	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 210	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): 5 of 6 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 6.? see exons ↓