Ventricular septal defect 2

Summary

Ventricular septal defect 2 (MONDO:0013748) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ventricular septal defect 2
Mondo ID	MONDO:0013748
OMIM	614431
UMLS	C3280783
MedGen	482413
Is cancer (heuristic)	no

Also known as: CITED2 ventricular septal defect (disease) · ventricular septal defect (disease) caused by mutation in CITED2 · ventricular septal defect 2 · ventricular septal defect type 2 · VSD2

Data availability: 5 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 › ventricular septal defect › ventricular septal defect 2

Related subtypes (4): ventricular septal defect 1, ventricular septal defect 3, double outlet right ventricle, anterior deviation infundibular septum

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:

4 uncertain significance, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2671924	NM_006079.5(CITED2):c.388C>T (p.Pro130Ser)	CITED2	Uncertain significance	criteria provided, single submitter
3054446	NM_006079.5(CITED2):c.510_536dup (p.Gly180_Ser181insGlySerSerThrProGlyGlySerGly)	CITED2	Uncertain significance	criteria provided, single submitter
3779083	NM_006079.5(CITED2):c.697A>G (p.Ile233Val)	CITED2	Uncertain significance	criteria provided, single submitter
6721	NM_006079.5(CITED2):c.510_536del (p.163GSSTPGGSG[1])	CITED2	Uncertain significance	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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CITED2	HGNC:1987	ENSG00000164442	Q99967	Cbp/p300-interacting transactivator 2	gencc,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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CITED2	Other/Unknown	no		CITED

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
mucosa of stomach	1
stromal cell of endometrium	1
type B pancreatic cell	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CITED2	1,215

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CITED2	Q99967	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
TFAP2 (AP-2) family regulates transcription of other transcription factors	1	2855.0×	0.001	CITED2
Regulation of gene expression by Hypoxia-inducible Factor	1	951.7×	0.001	CITED2
Activation of the TFAP2 (AP-2) family of transcription factors	1	951.7×	0.001	CITED2
FOXO-mediated transcription of cell death genes	1	713.8×	0.001	CITED2

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
cranial nerve morphogenesis	1	16852.0×	0.002	CITED2
regulation of animal organ formation	1	8426.0×	0.002	CITED2
adrenal cortex formation	1	8426.0×	0.002	CITED2
cardiac neural crest cell development involved in heart development	1	5617.3×	0.003	CITED2
left/right pattern formation	1	3370.4×	0.003	CITED2
embryonic heart tube left/right pattern formation	1	2808.7×	0.003	CITED2
pulmonary artery morphogenesis	1	2808.7×	0.003	CITED2
embryonic process involved in female pregnancy	1	2106.5×	0.003	CITED2
determination of left/right asymmetry in lateral mesoderm	1	1872.4×	0.003	CITED2
response to fluid shear stress	1	1872.4×	0.003	CITED2
sex determination	1	1685.2×	0.003	CITED2
positive regulation of peroxisome proliferator activated receptor signaling pathway	1	1685.2×	0.003	CITED2
positive regulation of male gonad development	1	1685.2×	0.003	CITED2
endocardial cushion development	1	1404.3×	0.003	CITED2
lens morphogenesis in camera-type eye	1	1296.3×	0.003	CITED2
granulocyte differentiation	1	1203.7×	0.003	CITED2
left/right axis specification	1	1203.7×	0.003	CITED2
nodal signaling pathway	1	1123.5×	0.003	CITED2
embryonic camera-type eye morphogenesis	1	1123.5×	0.003	CITED2
trophectodermal cell differentiation	1	991.3×	0.003	CITED2
uterus development	1	802.5×	0.003	CITED2
embryonic placenta development	1	766.0×	0.003	CITED2
positive regulation of cell-cell adhesion	1	766.0×	0.003	CITED2
decidualization	1	674.1×	0.004	CITED2
bone morphogenesis	1	601.9×	0.004	CITED2
peripheral nervous system development	1	581.1×	0.004	CITED2
positive regulation of transforming growth factor beta receptor signaling pathway	1	526.6×	0.004	CITED2
erythrocyte development	1	526.6×	0.004	CITED2
positive regulation of cell cycle	1	443.5×	0.004	CITED2
ventricular septum morphogenesis	1	432.1×	0.004	CITED2

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
CITED2	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	CITED2

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)
CITED2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.