Atrial septal defect 9

Summary

Atrial septal defect 9 (MONDO:0013770) is a disease caused by GATA6 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: GATA6 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 21

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrial septal defect 9
Mondo ID	MONDO:0013770
OMIM	614475
DOID	DOID:0110114
UMLS	C3280943
MedGen	482573
GARD	0024949
Is cancer (heuristic)	no

Also known as: ASD9 · atrial heart septal defect caused by mutation in GATA6 · atrial heart septal defect type 9 · atrial septal defect 9 · atrial septal defect type 9 · GATA6 atrial heart septal defect

Data availability: 21 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 9

Related subtypes (14): Lutembacher syndrome, atrial septal defect 1, atrial septal defect 7, atrial septal defect 2, atrial septal defect 4, atrial septal defect 5, atrial septal defect 6, atrial septal defect 3, atrial septal defect 8, 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

21 retrieved; paginated sample, class counts are floors:

13 uncertain significance, 3 conflicting classifications of pathogenicity, 2 likely benign, 2 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3583188	NM_005257.6(GATA6):c.1135+2T>C	GATA6	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3899338	NM_005257.6(GATA6):c.1135+1G>A	GATA6	Likely pathogenic	criteria provided, single submitter
30210	NM_005257.6(GATA6):c.551G>A (p.Ser184Asn)	GATA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
412726	NM_005257.6(GATA6):c.1663C>G (p.Pro555Ala)	GATA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
999815	NM_005257.6(GATA6):c.660C>T (p.Gly220=)	GATA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1311036	NM_005257.6(GATA6):c.259C>T (p.Pro87Ser)	GATA6	Uncertain significance	criteria provided, multiple submitters, no conflicts
1805697	NM_005257.6(GATA6):c.1342C>T (p.His448Tyr)	GATA6	Uncertain significance	criteria provided, multiple submitters, no conflicts
2500038	NM_005257.6(GATA6):c.202G>C (p.Glu68Gln)	GATA6	Uncertain significance	criteria provided, single submitter
3236107	NM_005257.6(GATA6):c.1441C>A (p.Leu481Ile)	GATA6	Uncertain significance	criteria provided, single submitter
3583187	NM_005257.6(GATA6):c.37C>T (p.Arg13Cys)	GATA6	Uncertain significance	criteria provided, multiple submitters, no conflicts
3708782	NM_005257.6(GATA6):c.1105C>G (p.Pro369Ala)	GATA6	Uncertain significance	criteria provided, multiple submitters, no conflicts
472909	NM_005257.6(GATA6):c.1089G>T (p.Gln363His)	GATA6	Uncertain significance	criteria provided, multiple submitters, no conflicts
540131	NM_005257.6(GATA6):c.839G>C (p.Gly280Ala)	GATA6	Uncertain significance	criteria provided, multiple submitters, no conflicts
540134	NM_005257.6(GATA6):c.233T>C (p.Leu78Pro)	GATA6	Uncertain significance	criteria provided, multiple submitters, no conflicts
648863	NM_005257.6(GATA6):c.1027G>A (p.Ala343Thr)	GATA6	Uncertain significance	criteria provided, multiple submitters, no conflicts
857098	NM_005257.6(GATA6):c.706G>T (p.Gly236Cys)	GATA6	Uncertain significance	criteria provided, multiple submitters, no conflicts
863328	NM_005257.6(GATA6):c.367A>G (p.Thr123Ala)	GATA6	Uncertain significance	criteria provided, multiple submitters, no conflicts
949027	NM_005257.6(GATA6):c.1757C>T (p.Pro586Leu)	GATA6	Uncertain significance	criteria provided, multiple submitters, no conflicts
1583127	NM_005257.6(GATA6):c.525G>T (p.Ala175=)	GATA6	Likely benign	criteria provided, multiple submitters, no conflicts
240127	NM_005257.6(GATA6):c.1374C>T (p.Asn458=)	GATA6	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
700342	NM_005257.6(GATA6):c.735G>A (p.Gly245=)	GATA6	Likely benign	criteria provided, multiple submitters, no conflicts

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	atrioventricular septal defect 5	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.