structural congenital heart disease, multiple types - GATA4

Summary

structural congenital heart disease, multiple types - GATA4 (MONDO:0100009) is a disease caused by GATA4 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: GATA4 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	structural congenital heart disease, multiple types - GATA4
Mondo ID	MONDO:0100009
Is cancer (heuristic)	no

Data availability: 4 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › congenital heart disease › structural congenital heart disease, multiple types - GATA4

Related subtypes (22): congenital heart defects, multiple types, heart septal defect, tetralogy of fallot, heart defects-limb shortening syndrome, tricuspid atresia, patent ductus arteriosus, coronary artery congenital malformation, mitral atresia disorder, persistent truncus arteriosus, dextro-looped transposition of the great arteries, aortic valve atresia, congenital pulmonary veins anomaly, mehta lewis patton syndrome, GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes, GATA5-related congenital heart defects, RBFOX2-related congenital heart disorder, syndromic congenital heart disease, ACTC1-related distal arthrogryposis with congenital heart disease, HAND1 related congenital heart defect, HAND2 related congenital heart defect, TFAP2B-related congenital heart disease spectrum disorder, PLD1-related congenital heart disease

Subtypes (3): atrial septal defect 2, ventricular septal defect 1, atrioventricular septal defect 4

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

4 retrieved; paginated sample, class counts are floors:

3 benign/likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
139595	NM_001308093.3(GATA4):c.912+25G>A	GATA4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
433016	NM_001308093.3(GATA4):c.617-113T>C	GATA4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
433023	NM_001308093.3(GATA4):c.1149+177C>T	GATA4	Benign	criteria provided, multiple submitters, no conflicts
433024	NM_001308093.3(GATA4):c.*852G>A	GATA4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
GATA4	Definitive	Autosomal dominant	testicular anomalies with or without congenital heart disease	15

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GATA4	Orphanet:251071	8p23.1 microdeletion syndrome
GATA4	Orphanet:251510	46,XY partial gonadal dysgenesis
GATA4	Orphanet:3303	Tetralogy of Fallot
GATA4	Orphanet:334	Hereditary atrial fibrillation
GATA4	Orphanet:576232	Partial atrioventricular septal defect with ventricular hypoplasia
GATA4	Orphanet:99067	Complete atrioventricular septal defect with ventricular hypoplasia
GATA4	Orphanet:99068	Complete atrioventricular septal defect-tetralogy of Fallot
GATA4	Orphanet:99103	Atrial septal defect, ostium secundum type

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GATA4	HGNC:4173	ENSG00000136574	P43694	Transcription factor GATA-4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GATA4	Transcription factor GATA-4	Transcriptional activator that binds to the consensus sequence 5’-AGATAG-3’ and plays a key role in cardiac development and function.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GATA4	Transcription factor	no		Znf_GATA, GATA_N, Znf_NHR/GATA

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
duodenum	1
heart left ventricle	1
right atrium auricular region	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GATA4	85	broad	marker	right atrium auricular region, heart left ventricle, duodenum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GATA4	4,994

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GATA4	P43694	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of lateral plate mesoderm	1	2284.0×	0.003	GATA4
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)	1	878.5×	0.003	GATA4
YAP1- and WWTR1 (TAZ)-stimulated gene expression	1	761.3×	0.003	GATA4
Transcriptional regulation of testis differentiation	1	713.8×	0.003	GATA4
Formation of definitive endoderm	1	713.8×	0.003	GATA4
Physiological factors	1	671.8×	0.003	GATA4
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	1	601.0×	0.003	GATA4
Cardiogenesis	1	423.0×	0.003	GATA4
Developmental Lineage of Pancreatic Acinar Cells	1	300.5×	0.004	GATA4
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.005	GATA4
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.015	GATA4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
atrial septum secundum morphogenesis	1	8426.0×	0.002	GATA4
embryonic heart tube anterior/posterior pattern specification	1	5617.3×	0.002	GATA4
atrioventricular valve formation	1	4213.0×	0.002	GATA4
cardiac muscle tissue regeneration	1	4213.0×	0.002	GATA4
atrial septum primum morphogenesis	1	3370.4×	0.002	GATA4
atrioventricular node development	1	2808.7×	0.002	GATA4
cell growth involved in cardiac muscle cell development	1	2407.4×	0.002	GATA4
transdifferentiation	1	2106.5×	0.002	GATA4
cardiac ventricle morphogenesis	1	1872.4×	0.002	GATA4
embryonic foregut morphogenesis	1	1685.2×	0.002	GATA4
atrioventricular canal development	1	1532.0×	0.002	GATA4
intestinal epithelial cell differentiation	1	1532.0×	0.002	GATA4
endocardial cushion development	1	1404.3×	0.002	GATA4
cardiac right ventricle morphogenesis	1	1404.3×	0.002	GATA4
atrial septum morphogenesis	1	1296.3×	0.002	GATA4
regulation of cardiac muscle cell contraction	1	1123.5×	0.002	GATA4
response to vitamin A	1	1053.2×	0.002	GATA4
negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	1	936.2×	0.002	GATA4
endoderm development	1	624.1×	0.003	GATA4
negative regulation of apoptotic signaling pathway	1	561.7×	0.003	GATA4
negative regulation of cardiac muscle cell apoptotic process	1	543.6×	0.003	GATA4
ventricular septum development	1	495.6×	0.003	GATA4
positive regulation of vascular endothelial growth factor production	1	495.6×	0.003	GATA4
positive regulation of BMP signaling pathway	1	455.5×	0.004	GATA4
aortic valve morphogenesis	1	432.1×	0.004	GATA4
response to mechanical stimulus	1	300.9×	0.005	GATA4
cell fate commitment	1	295.6×	0.005	GATA4
heart looping	1	267.5×	0.005	GATA4
cellular response to glucose stimulus	1	267.5×	0.005	GATA4
negative regulation of autophagy	1	259.3×	0.005	GATA4

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GATA4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GATA4	5	Binding:5

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	GATA4

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GATA4	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.