GATA5

Chr 20ADAR

GATA binding protein 5

Also known as: CHTD5, GATAS, bB379O24.1

NCBI Gene: 140628 ENSG00000130700 UniProt: Q9BWX5 OMIM: 611496

GATA5 encodes a transcription factor containing two GATA-type zinc fingers that is required during cardiovascular development and plays an important role in smooth muscle cell diversity. Mutations cause multiple types of congenital heart defects with both autosomal dominant and autosomal recessive inheritance patterns reported. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.629), consistent with its role in essential cardiac development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a transcription factor that contains two GATA-type zinc fingers. The encoded protein is known to bind to hepatocyte nuclear factor-1alpha (HNF-1alpha), and this interaction is essential for cooperative activation of the intestinal lactase-phlorizin hydrolase promoter. In other organisms, similar proteins may be involved in the establishment of cardiac smooth muscle cell diversity. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismAD/ARLOEUF 0.631 OMIM phenotype

Clinical Summary— GATA5

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 76 VUS of 142 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.63LOEUF

pLI 0.285

Z-score 2.46

OE 0.24 (0.11–0.63)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.07Z-score

OE missense 0.78 (0.68–0.89)

146 obs / 187.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.11–0.63)

0≤0.351.4

Missense OE?0.78 (0.68–0.89)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 3 / 12.3Missense obs/exp: 146 / 187.3Syn Z: -0.03

This gene — mechanism propensity

0.6164th %ile

GOF

0.3689th %ile

LOF

0.70top 10%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). 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 · 20% of P/LP variants are LoF

DN1 literature citation

Literature Evidence

DNThe expression of the mutant inhibited wild-type-induced activation of the ANF promoter, suggesting that the mutant functions in a dominant-negative manner.1

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

References

1.PMID 22961344 ↗

ClinVar Variant Classifications

142 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic1

VUS76

Likely Benign49

Benign4

Conflicting5

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	4	0	0	4
Likely Pathogenic	1	0	0	0	1
VUS	4	69	3	0	76
Likely Benign	0	5	17	27	49
Benign	0	0	0	4	4
Conflicting	—				5
Total	5	78	20	31	139

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap GATA5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →