Atrioventricular septal defect 5

Summary

Atrioventricular septal defect 5 (MONDO:0013769) 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: 582

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrioventricular septal defect 5
Mondo ID	MONDO:0013769
OMIM	614474
UMLS	C3280939
MedGen	482569
GARD	0024948
Is cancer (heuristic)	no

Also known as: atrioventricular septal defect 5 · atrioventricular septal defect caused by mutation in GATA6 · atrioventricular septal defect type 5 · AVSD5 · GATA6 atrioventricular septal defect

Data availability: 582 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 › familial atrioventricular septal defect › atrioventricular septal defect 5

Related subtypes (5): atrioventricular septal defect 4, congenital heart defects, multiple types, 4, complete atrioventricular canal, partial atrioventricular canal, atrioventricular septal defect

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

582 retrieved; paginated sample, class counts are floors:

320 uncertain significance, 212 likely benign, 16 conflicting classifications of pathogenicity, 12 benign/likely benign, 12 pathogenic, 7 benign, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1382320	NM_005257.6(GATA6):c.1418_1424del (p.Lys473fs)	GATA6	Pathogenic	criteria provided, single submitter
1410108	NM_005257.6(GATA6):c.1321G>T (p.Gly441Ter)	GATA6	Pathogenic	criteria provided, single submitter
2038076	NM_005257.6(GATA6):c.358C>T (p.Gln120Ter)	GATA6	Pathogenic	criteria provided, single submitter
2807112	NM_005257.6(GATA6):c.616C>T (p.Gln206Ter)	GATA6	Pathogenic	criteria provided, single submitter
30206	NM_005257.6(GATA6):c.1457_1458del (p.Glu486fs)	GATA6	Pathogenic	criteria provided, single submitter
30213	NM_005257.6(GATA6):c.1366C>T (p.Arg456Cys)	GATA6	Pathogenic	criteria provided, multiple submitters, no conflicts
3647503	NM_005257.6(GATA6):c.1456_1468del (p.Glu486fs)	GATA6	Pathogenic	criteria provided, single submitter
3729421	NM_005257.6(GATA6):c.1151_1155del (p.Leu384fs)	GATA6	Pathogenic	criteria provided, single submitter
4731459	NM_005257.6(GATA6):c.1486A>T (p.Lys496Ter)	GATA6	Pathogenic	criteria provided, single submitter
653141	NM_005257.6(GATA6):c.1477C>T (p.Arg493Ter)	GATA6	Pathogenic	criteria provided, multiple submitters, no conflicts
833485	NC_000018.10:g.(?22168362)(22172289_?)del	GATA6	Pathogenic	criteria provided, single submitter
862125	NM_005257.6(GATA6):c.838G>T (p.Gly280Ter)	GATA6	Pathogenic	criteria provided, single submitter
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
4715633	NM_005257.6(GATA6):c.1429-2A>G	GATA6	Likely pathogenic	criteria provided, single submitter
1114408	NM_005257.6(GATA6):c.151G>A (p.Glu51Lys)	GATA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
211064	NM_005257.6(GATA6):c.1375G>A (p.Ala459Thr)	GATA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2195608	NM_005257.6(GATA6):c.151G>T (p.Glu51Ter)	GATA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
240129	NM_005257.6(GATA6):c.1605A>G (p.Gln535=)	GATA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2711575	NM_005257.6(GATA6):c.923C>A (p.Pro308His)	GATA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
30208	NM_005257.6(GATA6):c.592C>G (p.Leu198Val)	GATA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
30210	NM_005257.6(GATA6):c.551G>A (p.Ser184Asn)	GATA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
404061	NM_005257.6(GATA6):c.271C>T (p.Pro91Ser)	GATA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
412724	NM_005257.6(GATA6):c.1723G>C (p.Ala575Pro)	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
472910	NM_005257.6(GATA6):c.1320T>A (p.Leu440=)	GATA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
540130	NM_005257.6(GATA6):c.775G>A (p.Val259Ile)	GATA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
572520	NM_005257.6(GATA6):c.352C>T (p.Leu118Phe)	GATA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
835877	NM_005257.6(GATA6):c.969CCA[7] (p.His331_His333del)	GATA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
940915	NM_005257.6(GATA6):c.208G>A (p.Ala70Thr)	GATA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

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.