Atrial septal defect 2

Summary

Atrial septal defect 2 (MONDO:0011938) is a disease caused by GATA4 (GenCC Definitive), with 1 cohort gene and 2 clinical trials.

At a glance

• Causal gene: GATA4 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 35
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrial septal defect 2
Mondo ID	MONDO:0011938
MeSH	C538263
OMIM	607941
DOID	DOID:0110107
UMLS	C1842778
MedGen	334249
GARD	0024832
Is cancer (heuristic)	no

Also known as: ASD2 · atrial heart septal defect caused by mutation in GATA4 · atrial heart septal defect type 2 · atrial septal defect 2 · atrial septal defect type 2 · GATA4 atrial heart septal defect

Data availability: 35 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › congenital heart disease › heart septal defect › atrial septal defect › atrial septal defect 2

Related subtypes (14): Lutembacher syndrome, atrial septal defect 1, atrial septal defect 7, atrial septal defect 4, atrial septal defect 5, atrial septal defect 6, atrial septal defect 3, atrial septal defect 8, atrial septal defect 9, atrial septal defect, ostium secundum type, atrial septal defect, coronary sinus type, atrial septal defect, sinus venosus type, atrial septal defect, ostium primum type, patent foramen ovale

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

35 retrieved; paginated sample, class counts are floors:

14 uncertain significance, 7 conflicting classifications of pathogenicity, 6 pathogenic, 4 likely pathogenic, 2 pathogenic/likely pathogenic, 1 benign/likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1029405	NM_001308093.3(GATA4):c.851G>A (p.Arg284His)	GATA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1338850	NM_001308093.3(GATA4):c.691C>T (p.Arg231Ter)	GATA4	Pathogenic	criteria provided, multiple submitters, no conflicts
1452170	NM_001308093.3(GATA4):c.54C>G (p.Tyr18Ter)	GATA4	Pathogenic	criteria provided, single submitter
30098	NM_001308093.3(GATA4):c.889G>T (p.Gly297Cys)	GATA4	Pathogenic	no assertion criteria provided
4056393	NM_001308093.3(GATA4):c.786+1G>A	GATA4	Pathogenic	criteria provided, single submitter
9030	NM_001308093.3(GATA4):c.889G>A (p.Gly297Ser)	GATA4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9031	NM_001308093.3(GATA4):c.1078del (p.Glu360fs)	GATA4	Pathogenic	no assertion criteria provided
9032	NM_001308093.3(GATA4):c.155C>T (p.Ser52Phe)	GATA4	Pathogenic	no assertion criteria provided
1805431	NM_001308093.3(GATA4):c.854_856del (p.Arg285_Asn286delinsHis)	GATA4	Likely pathogenic	criteria provided, single submitter
2582576	NM_001308093.3(GATA4):c.799C>T (p.Arg267Ter)	GATA4	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3066303	NM_001308093.3(GATA4):c.896A>G (p.Tyr299Cys)	GATA4	Likely pathogenic	criteria provided, single submitter
4056434	NM_001308093.3(GATA4):c.822C>A (p.Asn274Lys)	GATA4	Likely pathogenic	criteria provided, single submitter
30099	NM_001308093.3(GATA4):c.487C>T (p.Pro163Ser)	GATA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
30103	NM_001308093.3(GATA4):c.1223C>A (p.Pro408Gln)	GATA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
30109	NM_001308093.3(GATA4):c.931A>G (p.Met311Val)	GATA4	Conflicting classifications of pathogenicity	no assertion criteria provided
44336	NM_001308093.3(GATA4):c.825C>T (p.Cys275=)	GATA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
545667	NM_001308093.3(GATA4):c.961C>T (p.Arg321Trp)	GATA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
870470	NM_001308093.3(GATA4):c.1312G>A (p.Gly438Arg)	GATA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
9034	NM_001308093.3(GATA4):c.1276G>A (p.Asp426Asn)	GATA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1197085	NM_001308093.3(GATA4):c.1240C>G (p.Pro414Ala)	GATA4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1253738	NM_001308093.3(GATA4):c.841A>T (p.Thr281Ser)	GATA4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1314160	NM_001308093.3(GATA4):c.1149G>A (p.Gln383=)	GATA4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1372032	NM_001308093.3(GATA4):c.623T>C (p.Met208Thr)	GATA4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1444319	NM_001308093.3(GATA4):c.343G>T (p.Gly115Trp)	GATA4	Uncertain significance	criteria provided, multiple submitters, no conflicts
30108	NM_001308093.3(GATA4):c.842C>T (p.Thr281Met)	GATA4	Uncertain significance	criteria provided, single submitter
3595040	NM_001308093.3(GATA4):c.790G>A (p.Ala264Thr)	GATA4	Uncertain significance	criteria provided, multiple submitters, no conflicts
424039	NM_001308093.3(GATA4):c.1315G>A (p.Asp439Asn)	GATA4	Uncertain significance	criteria provided, multiple submitters, no conflicts
429341	NM_001308093.3(GATA4):c.392C>G (p.Ala131Gly)	GATA4	Uncertain significance	criteria provided, multiple submitters, no conflicts
472776	NM_001308093.3(GATA4):c.263G>T (p.Gly88Val)	GATA4	Uncertain significance	criteria provided, multiple submitters, no conflicts
472784	NM_001308093.3(GATA4):c.942G>T (p.Glu314Asp)	GATA4	Uncertain significance	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	atrial septal defect 2	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: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03867708	Not specified	WITHDRAWN	Outcomes of Transcatheter ASD Closure Guided by 3D-TEE
NCT05552144	Not specified	COMPLETED	Documenting Toothbrushing Experiences of Caregivers Who Care for Children With Autism Spectrum Disorders