GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes

Summary

GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes (MONDO:0100540) is a disease caused by GATA6 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: GATA6 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes
Mondo ID	MONDO:0100540
Is cancer (heuristic)	no

Also known as: GATA6 related congenital heart disease with or without pancreatic agenesis or neonatal diabetes

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › congenital heart disease › GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes

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, structural congenital heart disease, multiple types - GATA4, 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 (2): atrioventricular septal defect 5, atrial septal defect 9

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

2 retrieved; paginated sample, class counts are floors:

2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3370395	NM_005257.6(GATA6):c.1385A>G (p.Glu462Gly)	GATA6	Uncertain significance	criteria provided, single submitter
4531688	NM_005257.6(GATA6):c.1447A>G (p.Met483Val)	GATA6	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · 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
GATA6	Definitive	Autosomal dominant	pancreatic hypoplasia-diabetes-congenital heart disease syndrome	16

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GATA6	Orphanet:2140	Congenital diaphragmatic hernia
GATA6	Orphanet:2255	Pancreatic hypoplasia-diabetes-congenital heart disease syndrome
GATA6	Orphanet:3303	Tetralogy of Fallot
GATA6	Orphanet:334	Hereditary atrial fibrillation
GATA6	Orphanet:665044	Common arterial trunk with aortic dominance
GATA6	Orphanet:665058	Common arterial trunk with pulmonary dominance and interrupted aortic arch
GATA6	Orphanet:99067	Complete atrioventricular septal defect with ventricular hypoplasia
GATA6	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
GATA6	HGNC:4174	ENSG00000141448	Q92908	Transcription factor GATA-6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GATA6	Transcription factor GATA-6	Transcriptional activator.

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)
GATA6	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
germinal epithelium of ovary	1
jejunal mucosa	1
parietal pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GATA6	204	ubiquitous	marker	germinal epithelium of ovary, parietal pleura, jejunal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GATA6	49

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GATA6	Q92908	53.48

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation	1	1142.0×	0.003	GATA6
Formation of definitive endoderm	1	713.8×	0.003	GATA6
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	1	601.0×	0.003	GATA6
Cardiogenesis	1	423.0×	0.003	GATA6
Surfactant metabolism	1	368.4×	0.003	GATA6
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.015	GATA6

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
negative regulation of transforming growth factor beta2 production	1	16852.0×	1e-03	GATA6
tube morphogenesis	1	16852.0×	1e-03	GATA6
negative regulation of sebum secreting cell proliferation	1	16852.0×	1e-03	GATA6
regulation of antimicrobial humoral response	1	8426.0×	0.001	GATA6
endodermal cell fate determination	1	8426.0×	0.001	GATA6
sebaceous gland cell differentiation	1	5617.3×	0.001	GATA6
positive regulation of cardiac muscle myoblast proliferation	1	5617.3×	0.001	GATA6
cardiac vascular smooth muscle cell differentiation	1	4213.0×	0.001	GATA6
skin epidermis development	1	4213.0×	0.001	GATA6
animal organ formation	1	3370.4×	0.001	GATA6
club cell differentiation	1	3370.4×	0.001	GATA6
atrioventricular node development	1	2808.7×	0.001	GATA6
negative regulation of transforming growth factor beta1 production	1	2808.7×	0.001	GATA6
G1 to G0 transition involved in cell differentiation	1	2808.7×	0.001	GATA6
cellular response to gonadotropin stimulus	1	2808.7×	0.001	GATA6
pancreatic A cell differentiation	1	2407.4×	0.001	GATA6
sinoatrial node development	1	2106.5×	0.001	GATA6
type B pancreatic cell differentiation	1	2106.5×	0.001	GATA6
lung saccule development	1	2106.5×	0.001	GATA6
type II pneumocyte differentiation	1	2106.5×	0.001	GATA6
atrioventricular canal development	1	1532.0×	0.001	GATA6
intestinal epithelial cell differentiation	1	1532.0×	0.001	GATA6
response to growth factor	1	1404.3×	0.002	GATA6
cardiac muscle hypertrophy in response to stress	1	1053.2×	0.002	GATA6
smooth muscle cell differentiation	1	887.0×	0.002	GATA6
heart contraction	1	766.0×	0.002	GATA6
cardiac muscle cell differentiation	1	674.1×	0.003	GATA6
outflow tract septum morphogenesis	1	648.1×	0.003	GATA6
positive regulation of cardiac muscle cell proliferation	1	624.1×	0.003	GATA6
cardiac muscle cell proliferation	1	581.1×	0.003	GATA6

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GATA6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	GATA6

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)
GATA6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.