Char syndrome

Summary

Char syndrome (MONDO:0008209) is a disease caused by TFAP2B (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TFAP2B (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 27
• Phenotypes (HPO): 28

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		109	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

28 HPO clinical features (Orphanet curated; top 28 by frequency):

HPO ID	Term	Frequency
HP:0000207	Triangular mouth	Very frequent (80-99%)
HP:0000232	Everted lower lip vermilion	Very frequent (80-99%)
HP:0000272	Malar flattening	Very frequent (80-99%)
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0000322	Short philtrum	Very frequent (80-99%)
HP:0000457	Depressed nasal ridge	Very frequent (80-99%)
HP:0000494	Downslanted palpebral fissures	Very frequent (80-99%)
HP:0000508	Ptosis	Very frequent (80-99%)
HP:0001643	Patent ductus arteriosus	Very frequent (80-99%)
HP:0005280	Depressed nasal bridge	Very frequent (80-99%)
HP:0012471	Thick vermilion border	Very frequent (80-99%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0004220	Short middle phalanx of the 5th finger	Frequent (30-79%)
HP:0006159	Mesoaxial hand polydactyly	Frequent (30-79%)
HP:0006349	Agenesis of permanent teeth	Occasional (5-29%)
HP:0000269	Prominent occiput	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000545	Myopia	Occasional (5-29%)
HP:0001161	Hand polydactyly	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001629	Ventricular septal defect	Occasional (5-29%)
HP:0001770	Toe syndactyly	Occasional (5-29%)
HP:0002360	Sleep abnormality	Occasional (5-29%)
HP:0002558	Supernumerary nipple	Occasional (5-29%)
HP:0004218	Symphalangism of the 5th finger	Occasional (5-29%)
HP:0006335	Persistence of primary teeth	Occasional (5-29%)
HP:0010112	Mesoaxial foot polydactyly	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Char syndrome
Mondo ID	MONDO:0008209
MeSH	C566815
OMIM	169100
Orphanet	46627
DOID	DOID:0060563
SNOMED CT	703534001
UMLS	C1868570
MedGen	358356
GARD	0001237
Is cancer (heuristic)	no

Also known as: CHAR · Char syndrome · patent ductus arteriosus with facial dysmorphism and abnormal fifth digits

Data availability: 27 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › patent ductus arteriosus › Char syndrome

Related subtypes (3): patent ductus arteriosus 2, patent ductus arteriosus 3, PDA1

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

27 retrieved; paginated sample, class counts are floors:

12 uncertain significance, 6 pathogenic, 3 likely pathogenic, 3 not provided, 2 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
21359	NM_003221.4(TFAP2B):c.601+5G>A	TFAP2B	Pathogenic	no assertion criteria provided
599040	NM_003221.4(TFAP2B):c.650del (p.Gly217fs)	TFAP2B	Pathogenic	criteria provided, single submitter
8039	NM_003221.4(TFAP2B):c.824C>A (p.Ala275Asp)	TFAP2B	Pathogenic	criteria provided, single submitter
8041	NM_003221.4(TFAP2B):c.706C>T (p.Arg236Cys)	TFAP2B	Pathogenic	no assertion criteria provided
8042	NM_003221.4(TFAP2B):c.706C>A (p.Arg236Ser)	TFAP2B	Pathogenic	no assertion criteria provided
8043	NM_003221.4(TFAP2B):c.854G>A (p.Arg285Gln)	TFAP2B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8044	NM_003221.4(TFAP2B):c.218C>G (p.Pro73Arg)	TFAP2B	Pathogenic	no assertion criteria provided
1326927	NM_003221.4(TFAP2B):c.707G>A (p.Arg236His)	TFAP2B	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2627564	NM_003221.4(TFAP2B):c.981C>A (p.Cys327Ter)	TFAP2B	Likely pathogenic	criteria provided, single submitter
8040	NM_003221.4(TFAP2B):c.898C>T (p.Arg300Cys)	TFAP2B	Likely pathogenic	criteria provided, single submitter
1028094	NM_003221.4(TFAP2B):c.1105G>C (p.Asp369His)	TFAP2B	Uncertain significance	criteria provided, single submitter
1360116	NM_003221.4(TFAP2B):c.92A>G (p.Asp31Gly)	TFAP2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1803831	NM_003221.4(TFAP2B):c.1302C>G (p.Asn434Lys)	TFAP2B	Uncertain significance	criteria provided, single submitter
2502263	NM_003221.4(TFAP2B):c.811G>C (p.Val271Leu)	TFAP2B	Uncertain significance	criteria provided, single submitter
2572520	NM_003221.4(TFAP2B):c.805G>A (p.Gly269Ser)	TFAP2B	Uncertain significance	criteria provided, single submitter
2580212	NM_003221.4(TFAP2B):c.541-3_541-2del	TFAP2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
3065368	NM_003221.4(TFAP2B):c.540+7ACAA[3]	TFAP2B	Uncertain significance	criteria provided, single submitter
3376356	NM_003221.4(TFAP2B):c.796T>C (p.Ser266Pro)	TFAP2B	Uncertain significance	criteria provided, single submitter
3376438	NM_003221.4(TFAP2B):c.265G>A (p.Val89Ile)	TFAP2B	Uncertain significance	criteria provided, single submitter
374174	NM_003221.4(TFAP2B):c.830C>G (p.Ser277Trp)	TFAP2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892642	NM_003221.4(TFAP2B):c.83A>G (p.Asp28Gly)	TFAP2B	Uncertain significance	criteria provided, single submitter
599234	NM_003221.4(TFAP2B):c.917C>T (p.Thr306Met)	TFAP2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1273651	NC_000006.12:g.50818858G>A	TFAP2B	Benign	criteria provided, multiple submitters, no conflicts
258985	NM_003221.4(TFAP2B):c.540+7ACAA[5]	TFAP2B	Benign	criteria provided, multiple submitters, no conflicts
21358	NM_003221.4(TFAP2B):c.444C>A (p.Asp148Glu)	TFAP2B	not provided	no classification provided
21360	NM_003221.4(TFAP2B):c.772T>G (p.Ser258Ala)	TFAP2B	not provided	no classification provided
21361	NM_003221.4(TFAP2B):c.822-1G>C	TFAP2B	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
TFAP2B	Definitive	Autosomal dominant	Char syndrome	6

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	gencc,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.