Atrial septal defect 1

Summary

Atrial septal defect 1 (MONDO:0007172) is a disease with 5 cohort genes.

At a glance

• Cohort genes: 5
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrial septal defect 1
Mondo ID	MONDO:0007172
OMIM	108800
DOID	DOID:0110106
UMLS	C1862389
MedGen	349495
GARD	0024529
Is cancer (heuristic)	no

Also known as: ASD1 · atrial heart septal defect type 1 · atrial septal defect 1

Data availability: 5 ClinVar variants.

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 1

Related subtypes (14): Lutembacher syndrome, 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 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

5 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1703211	NM_001200.4(BMP2):c.1052C>G (p.Ser351Cys)	BMP2	Pathogenic	no assertion criteria provided
235885	NM_181486.4(TBX5):c.444G>A (p.Trp148Ter)	TBX5	Pathogenic	no assertion criteria provided
1300138	NM_003238.6(TGFB2):c.1012C>A (p.Pro338Thr)	TGFB2	Pathogenic	no assertion criteria provided
370040	NM_001018005.2(TPM1):c.686C>T (p.Ser229Phe)	TPM1	Likely pathogenic	no assertion criteria provided
1174513	NM_001349338.3(FOXP1):c.1778C>A (p.Pro593His)	FOXP1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 11 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BMP2	Orphanet:261295	20p12.3 microdeletion syndrome
BMP2	Orphanet:93396	Brachydactyly type A2
TBX5	Orphanet:101016	Romano-Ward syndrome
TBX5	Orphanet:392	Holt-Oram syndrome
TGFB2	Orphanet:60030	Loeys-Dietz syndrome
TGFB2	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
TPM1	Orphanet:154	Familial isolated dilated cardiomyopathy
TPM1	Orphanet:54260	Left ventricular noncompaction
FOXP1	Orphanet:391372	FOXP1 Syndrome
FOXP1	Orphanet:52417	MALT lymphoma
FOXP1	Orphanet:585877	B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BMP2	HGNC:1069	ENSG00000125845	P12643	Bone morphogenetic protein 2	clinvar
TBX5	HGNC:11604	ENSG00000089225	Q99593	T-box transcription factor TBX5	clinvar
TGFB2	HGNC:11768	ENSG00000092969	P61812	Transforming growth factor beta-2 proprotein	clinvar
TPM1	HGNC:12010	ENSG00000140416	P09493	Tropomyosin alpha-1 chain	clinvar
FOXP1	HGNC:3823	ENSG00000114861	Q9H334	Forkhead box protein P1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BMP2	Bone morphogenetic protein 2	Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis.
TBX5	T-box transcription factor TBX5	DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation.
TGFB2	Transforming growth factor beta-2 proprotein	Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively.
TPM1	Tropomyosin alpha-1 chain	Binds to actin filaments in muscle and non-muscle cells.
FOXP1	Forkhead box protein P1	Transcriptional repressor.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 3 · 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	2	3.3×	0.229
Other/Unknown	3	1.1×	0.608

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BMP2	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like
TBX5	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
TGFB2	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGFb2
TPM1	Other/Unknown	no		Tropomyosin
FOXP1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_2, FOXP-CC

Expression context

Cohort genes with no expression data: 0.

5 cohort genes 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	2
pancreatic ductal cell	2
pigmented layer of retina	1
buccal mucosa cell	1
cardiac muscle of right atrium	1
tendon of biceps brachii	1
calcaneal tendon	1
tendon	1
heart right ventricle	1
left ventricle myocardium	1
myocardium	1
cardia of stomach	1
oviduct epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BMP2	238	broad	marker	cartilage tissue, pancreatic ductal cell, pigmented layer of retina
TBX5	129	broad	marker	tendon of biceps brachii, cardiac muscle of right atrium, buccal mucosa cell
TGFB2	206	ubiquitous	marker	calcaneal tendon, tendon, cartilage tissue
TPM1	305	ubiquitous	marker	left ventricle myocardium, heart right ventricle, myocardium
FOXP1	256	ubiquitous	marker	pancreatic ductal cell, oviduct epithelium, cardia of stomach

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TPM1	3,514
BMP2	3,131
FOXP1	2,939
TBX5	2,250
TGFB2	43

Intra-cohort edges

A	B	Sources
BMP2	TGFB2	biogrid_interaction, intact

Structural data

PDB: 5 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BMP2	P12643	21
TPM1	P09493	14
TGFB2	P61812	11
TBX5	Q99593	4
FOXP1	Q9H334	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 29. Enrichment computed across 5 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Elastic fibre formation	2	134.3×	0.001	BMP2, TGFB2
Molecules associated with elastic fibres	2	123.5×	0.001	BMP2, TGFB2
Signaling by TGFB family members	2	46.1×	0.007	BMP2, TGFB2
Extracellular matrix organization	2	25.2×	0.018	BMP2, TGFB2
TGFBR3 regulates TGF-beta signaling	1	285.5×	0.020	TGFB2
YAP1- and WWTR1 (TAZ)-stimulated gene expression	1	152.3×	0.031	TBX5
Physiological factors	1	134.3×	0.031	TBX5
Transcriptional regulation of pluripotent stem cells	1	108.8×	0.033	FOXP1
Cardiogenesis	1	84.6×	0.035	TBX5
Signaling by TGFBR3	1	73.7×	0.035	TGFB2
Signaling by BMP	1	71.4×	0.035	BMP2
TGF-beta receptor signaling activates SMADs	1	65.3×	0.035	TGFB2
Striated Muscle Contraction	1	61.7×	0.035	TPM1
Smooth Muscle Contraction	1	53.1×	0.035	TPM1
Transcriptional regulation by RUNX2	1	50.8×	0.035	BMP2
RNA Polymerase II Transcription	2	9.0×	0.035	BMP2, TBX5
Signaling by TGF-beta Receptor Complex	1	40.1×	0.042	TGFB2
Regulation of RUNX2 expression and activity	1	36.2×	0.043	BMP2
Gene expression (Transcription)	2	7.1×	0.043	BMP2, TBX5
Response to elevated platelet cytosolic Ca2+	1	32.6×	0.044	TGFB2
ECM proteoglycans	1	30.1×	0.045	TGFB2
Generic Transcription Pathway	2	6.0×	0.050	BMP2, TBX5
Cardiac conduction	1	21.8×	0.056	TBX5
Platelet activation, signaling and aggregation	1	21.1×	0.056	TGFB2
Platelet degranulation	1	17.6×	0.065	TGFB2
Muscle contraction	1	15.4×	0.070	TBX5
Signal Transduction	2	4.1×	0.085	BMP2, TGFB2
Hemostasis	1	7.2×	0.136	TGFB2
Developmental Biology	1	2.9×	0.301	TBX5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
atrioventricular valve morphogenesis	3	722.2×	1e-06	BMP2, TBX5, TGFB2
positive regulation of cardioblast differentiation	2	1685.2×	5e-05	TBX5, TGFB2
pericardium development	2	749.0×	2e-04	BMP2, TBX5
atrial septum morphogenesis	2	518.5×	3e-04	TBX5, TGFB2
cardiac epithelial to mesenchymal transition	2	481.5×	3e-04	BMP2, TGFB2
endocardial cushion morphogenesis	2	337.0×	6e-04	BMP2, TGFB2
heart development	3	47.2×	7e-04	BMP2, TBX5, TGFB2
cardiac muscle cell proliferation	2	232.4×	8e-04	TBX5, TGFB2
negative regulation of gene expression	3	41.4×	8e-04	BMP2, TGFB2, FOXP1
embryonic limb morphogenesis	2	160.5×	0.001	TBX5, TGFB2
positive regulation of SMAD protein signal transduction	2	153.2×	0.001	BMP2, TGFB2
heart morphogenesis	2	149.8×	0.001	BMP2, TGFB2
inner ear development	2	149.8×	0.001	BMP2, TGFB2
osteoclast differentiation	2	137.6×	0.002	BMP2, FOXP1
positive regulation of epithelial to mesenchymal transition	2	127.2×	0.002	BMP2, TGFB2
epithelial to mesenchymal transition	2	124.8×	0.002	BMP2, TGFB2
positive regulation of miRNA transcription	2	116.2×	0.002	BMP2, TGFB2
negative regulation of cell population proliferation	3	25.3×	0.002	BMP2, TBX5, TGFB2
wound healing	2	91.1×	0.003	TGFB2, TPM1
positive regulation of heart rate by epinephrine	1	3370.4×	0.003	TPM1
negative regulation of calcium-independent cell-cell adhesion	1	3370.4×	0.003	BMP2
regulation of timing of catagen	1	3370.4×	0.003	TGFB2
cell migration involved in coronary vasculogenesis	1	3370.4×	0.003	TBX5
positive regulation of activation-induced cell death of T cells	1	3370.4×	0.003	TGFB2
regulation of macrophage colony-stimulating factor production	1	3370.4×	0.003	FOXP1
regulation of apoptotic process involved in outflow tract morphogenesis	1	3370.4×	0.003	TGFB2
positive regulation of cardiac conduction	1	3370.4×	0.003	TBX5
negative regulation of epithelial to mesenchymal transition involved in endocardial cushion formation	1	3370.4×	0.003	TGFB2
endodermal-mesodermal cell signaling	1	1685.2×	0.004	BMP2
cardiac atrium formation	1	1685.2×	0.004	BMP2

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 5 evidence-associated genes (80%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TGFB2	1	2
BMP2	0	0
TBX5	0	0
TPM1	0	0
FOXP1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GALUNISERTIB	2	TGFB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
BMP2	22	Binding:18, Functional:4
TGFB2	3	Binding:3
TPM1	3	Binding:3
TBX5	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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.

Compound	Max phase	Cohort target (bioactivity)
GALUNISERTIB	2	TGFB2

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	1	TGFB2
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	BMP2, TBX5, TPM1, FOXP1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BMP2	22	—
TBX5	1	—
TPM1	3	—
FOXP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.