TFAP2B-related congenital heart disease spectrum disorder

Summary

TFAP2B-related congenital heart disease spectrum disorder (MONDO:1010098) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	TFAP2B-related congenital heart disease spectrum disorder
Mondo ID	MONDO:1010098
Is cancer (heuristic)	no

Also known as: TFAP2B-related PDA and Char syndrome spectrum disorder

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › congenital heart disease › TFAP2B-related congenital heart disease spectrum disorder

Related subtypes (22): congenital heart defects, multiple types, heart septal defect, tetralogy of fallot, heart defects-limb shortening syndrome, tricuspid atresia, patent ductus arteriosus, coronary artery congenital malformation, mitral atresia disorder, persistent truncus arteriosus, dextro-looped transposition of the great arteries, aortic valve atresia, congenital pulmonary veins anomaly, mehta lewis patton syndrome, structural congenital heart disease, multiple types - GATA4, GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes, GATA5-related congenital heart defects, RBFOX2-related congenital heart disorder, syndromic congenital heart disease, ACTC1-related distal arthrogryposis with congenital heart disease, HAND1 related congenital heart defect, HAND2 related congenital heart defect, PLD1-related congenital heart disease

Subtypes (2): Char syndrome, patent ductus arteriosus 2

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

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4532031	NM_003221.4(TFAP2B):c.767G>A (p.Arg256Gln)	TFAP2B	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TFAP2B	Orphanet:46627	Char syndrome
TFAP2B	Orphanet:466729	Familial patent arterial duct

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
TFAP2B	HGNC:11743	ENSG00000008196	Q92481	Transcription factor AP-2-beta	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TFAP2B	Transcription factor AP-2-beta	Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.

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)
TFAP2B	Transcription factor	no		TF_AP2, TF_AP2_beta, TF_AP2_C

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
cauda epididymis	1
corpus epididymis	1
oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TFAP2B	128	broad	marker	corpus epididymis, cauda epididymis, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TFAP2B	1,380

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TFAP2B	Q92481	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. 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
Negative regulation of activity of TFAP2 (AP-2) family transcription factors	1	1142.0×	0.004	TFAP2B
Activation of the TFAP2 (AP-2) family of transcription factors	1	951.7×	0.004	TFAP2B
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	761.3×	0.004	TFAP2B
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1	634.4×	0.004	TFAP2B
Specification of the neural plate border	1	634.4×	0.004	TFAP2B
SUMOylation of transcription factors	1	571.0×	0.004	TFAP2B
Gastrulation	1	259.6×	0.008	TFAP2B
SUMO E3 ligases SUMOylate target proteins	1	178.4×	0.010	TFAP2B
SUMOylation	1	163.1×	0.010	TFAP2B
RNA Polymerase II Transcription	1	22.5×	0.067	TFAP2B
Post-translational protein modification	1	19.2×	0.070	TFAP2B
Gene expression (Transcription)	1	17.8×	0.070	TFAP2B
Generic Transcription Pathway	1	15.1×	0.074	TFAP2B
Developmental Biology	1	14.5×	0.074	TFAP2B
Metabolism of proteins	1	12.4×	0.081	TFAP2B

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
metanephric nephron development	1	8426.0×	0.002	TFAP2B
distal tubule development	1	5617.3×	0.002	TFAP2B
collecting duct development	1	4213.0×	0.002	TFAP2B
ductus arteriosus closure	1	3370.4×	0.002	TFAP2B
hindlimb morphogenesis	1	2808.7×	0.002	TFAP2B
forelimb morphogenesis	1	2106.5×	0.002	TFAP2B
regulation of BMP signaling pathway	1	1203.7×	0.003	TFAP2B
smooth muscle tissue development	1	1053.2×	0.003	TFAP2B
sympathetic nervous system development	1	936.2×	0.003	TFAP2B
aorta morphogenesis	1	887.0×	0.003	TFAP2B
retina layer formation	1	648.1×	0.004	TFAP2B
skin development	1	443.5×	0.006	TFAP2B
regulation of cell differentiation	1	432.1×	0.006	TFAP2B
regulation of insulin secretion	1	391.9×	0.006	TFAP2B
positive regulation of neuron apoptotic process	1	271.8×	0.008	TFAP2B
glucose metabolic process	1	255.3×	0.008	TFAP2B
neuron apoptotic process	1	185.2×	0.010	TFAP2B
fat cell differentiation	1	181.2×	0.010	TFAP2B
kidney development	1	140.4×	0.012	TFAP2B
regulation of cell population proliferation	1	115.4×	0.013	TFAP2B
negative regulation of neuron apoptotic process	1	110.9×	0.013	TFAP2B
transcription by RNA polymerase II	1	70.5×	0.020	TFAP2B
response to xenobiotic stimulus	1	69.1×	0.020	TFAP2B
nervous system development	1	45.9×	0.028	TFAP2B
negative regulation of cell population proliferation	1	42.1×	0.029	TFAP2B
negative regulation of apoptotic process	1	34.8×	0.034	TFAP2B
positive regulation of cell population proliferation	1	33.6×	0.034	TFAP2B
negative regulation of DNA-templated transcription	1	31.6×	0.035	TFAP2B
positive regulation of DNA-templated transcription	1	27.9×	0.038	TFAP2B
negative regulation of transcription by RNA polymerase II	1	17.7×	0.058	TFAP2B

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
TFAP2B	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	TFAP2B

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)
TFAP2B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.