Atrial septal defect 8

Summary

Atrial septal defect 8 (MONDO:0013750) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrial septal defect 8
Mondo ID	MONDO:0013750
OMIM	614433
DOID	DOID:0110113
UMLS	C3280790
MedGen	482420
GARD	0024945
Is cancer (heuristic)	no

Also known as: ASD8 · atrial heart septal defect caused by mutation in CITED2 · atrial heart septal defect type 8 · atrial septal defect 8 · atrial septal defect type 8 · CITED2 atrial heart septal defect

Data availability: 7 ClinVar variants · 1 GenCC gene-disease record.

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 8

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 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

7 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
6722	CITED2, 27-BP INS, NT534	CITED2	Pathogenic	no assertion criteria provided
804240	NM_006079.5(CITED2):c.701A>C (p.Glu234Ala)	CITED2	Likely pathogenic	criteria provided, single submitter
1033069	NM_006079.5(CITED2):c.114CCA[1] (p.His39del)	CITED2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1804911	NM_006079.5(CITED2):c.119AGC[3] (p.Gln43del)	CITED2	Uncertain significance	criteria provided, single submitter
3064915	NM_006079.5(CITED2):c.754G>T (p.Glu252Ter)	CITED2	Uncertain significance	criteria provided, single submitter
1702936	NM_001719.3(BMP7):c.945G>A (p.Met315Ile)	BMP7	Benign	criteria provided, single submitter
6723	NM_006079.5(CITED2):c.581GCGGCA[2] (p.196SG[1])	CITED2	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 4 · 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
CITED2	Moderate	Autosomal dominant	atrial septal defect 8	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CITED2	Orphanet:101063	Situs inversus totalis
CITED2	Orphanet:3303	Tetralogy of Fallot
CITED2	Orphanet:99103	Atrial septal defect, ostium secundum type
CITED2	Orphanet:99105	Atrial septal defect, sinus venosus type

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CITED2	HGNC:1987	ENSG00000164442	Q99967	Cbp/p300-interacting transactivator 2	gencc,clinvar
BMP7	HGNC:1074	ENSG00000101144	P18075	Bone morphogenetic protein 7	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CITED2	Cbp/p300-interacting transactivator 2	Transcriptional coactivator of the p300/CBP-mediated transcription complex.
BMP7	Bone morphogenetic protein 7	Growth factor of the TGF-beta superfamily that plays important role in various biological processes, including embryogenesis, hematopoiesis, neurogenesis and skeletal morphogenesis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CITED2	Other/Unknown	no		CITED
BMP7	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
mucosa of stomach	1
stromal cell of endometrium	1
type B pancreatic cell	1
endometrium epithelium	1
pigmented layer of retina	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CITED2	284	ubiquitous	marker	stromal cell of endometrium, type B pancreatic cell, mucosa of stomach
BMP7	243	broad	marker	pigmented layer of retina, ventricular zone, endometrium epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BMP7	3,134
CITED2	1,215

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CITED2	Q99967	4
BMP7	P18075	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TFAP2 (AP-2) family regulates transcription of other transcription factors	1	1427.5×	0.006	CITED2
Transcriptional regulation of brown and beige adipocyte differentiation	1	571.0×	0.006	BMP7
Regulation of gene expression by Hypoxia-inducible Factor	1	475.8×	0.006	CITED2
Activation of the TFAP2 (AP-2) family of transcription factors	1	475.8×	0.006	CITED2
FOXO-mediated transcription of cell death genes	1	356.9×	0.006	CITED2
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	1	190.3×	0.009	BMP7
Elastic fibre formation	1	167.9×	0.009	BMP7
Molecules associated with elastic fibres	1	154.3×	0.009	BMP7
Adipogenesis	1	78.2×	0.016	BMP7
Extracellular matrix organization	1	31.6×	0.035	BMP7
Developmental Biology	1	7.2×	0.134	BMP7

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
embryonic camera-type eye morphogenesis	2	1123.5×	9e-05	CITED2, BMP7
cranial nerve morphogenesis	1	8426.0×	0.002	CITED2
negative regulation of mesenchymal cell apoptotic process involved in nephron morphogenesis	1	8426.0×	0.002	BMP7
mesenchymal cell apoptotic process involved in nephron morphogenesis	1	8426.0×	0.002	BMP7
regulation of animal organ formation	1	4213.0×	0.002	CITED2
adrenal cortex formation	1	4213.0×	0.002	CITED2
negative regulation of glomerular mesangial cell proliferation	1	4213.0×	0.002	BMP7
nephrogenic mesenchyme morphogenesis	1	4213.0×	0.002	BMP7
negative regulation of striated muscle cell apoptotic process	1	2808.7×	0.002	BMP7
neural fold elevation formation	1	2808.7×	0.002	BMP7
cardiac neural crest cell development involved in heart development	1	2808.7×	0.002	CITED2
monocyte aggregation	1	2808.7×	0.002	BMP7
metanephric mesenchyme morphogenesis	1	2808.7×	0.002	BMP7
metanephric mesenchymal cell proliferation involved in metanephros development	1	2808.7×	0.002	BMP7
positive regulation of hyaluranon cable assembly	1	2808.7×	0.002	BMP7
positive regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis	1	2808.7×	0.002	BMP7
cellular response to hypoxia	2	121.2×	0.002	CITED2, BMP7
heart development	2	78.8×	0.002	CITED2, BMP7
negative regulation of prostatic bud formation	1	2106.5×	0.003	BMP7
allantois development	1	2106.5×	0.003	BMP7
regulation of branching involved in prostate gland morphogenesis	1	1685.2×	0.003	BMP7
left/right pattern formation	1	1685.2×	0.003	CITED2
embryonic heart tube left/right pattern formation	1	1404.3×	0.003	CITED2
pulmonary artery morphogenesis	1	1404.3×	0.003	CITED2
regulation of removal of superoxide radicals	1	1404.3×	0.003	BMP7
positive regulation of gene expression	2	38.7×	0.003	CITED2, BMP7
negative regulation of mitotic nuclear division	1	1203.7×	0.003	BMP7
mesenchyme development	1	1203.7×	0.003	BMP7
pericardium morphogenesis	1	1053.2×	0.003	BMP7
ameloblast differentiation	1	1053.2×	0.003	BMP7

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
CITED2	0	0
BMP7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	CITED2, BMP7

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CITED2	0	—
BMP7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.