Persistent truncus arteriosus

Summary

Persistent truncus arteriosus (MONDO:0018072) is a disease with 4 cohort genes and 6 clinical trials.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 4
• ClinVar variants: 5
• Phenotypes (HPO): 36
• Clinical trials: 6

Clinical features

Epidemiology

Prevalence records

15 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	4.3	Worldwide	Validated
Prevalence at birth	1-9 / 100 000	4.8	Europe	Validated
Prevalence at birth	1-9 / 100 000	5.8	Belgium	Validated
Prevalence at birth	1-9 / 100 000	9.8	France	Validated
Prevalence at birth	1-9 / 100 000	5.8	Germany	Validated
Prevalence at birth	1-9 / 100 000	5.5	Hungary	Validated
Prevalence at birth	1-9 / 100 000	3.6	Ireland	Validated
Prevalence at birth	1-9 / 100 000	2.8	Italy	Validated
Prevalence at birth	1-9 / 100 000	5.8	Netherlands	Validated
Prevalence at birth	1-9 / 100 000	3.3	Norway	Validated
Prevalence at birth	1-9 / 100 000	2.2	Poland	Validated
Prevalence at birth	1-9 / 100 000	1.9	Spain	Validated
Prevalence at birth	1-5 / 10 000	12.6	Switzerland	Validated
Prevalence at birth	1-9 / 100 000	7.7	United Kingdom	Validated
Prevalence at birth	1-9 / 100 000	6.4	Ukraine	Validated

Signs & symptoms

Clinical features (HPO)

36 HPO clinical features (Orphanet curated; top 36 by frequency):

HPO ID	Term	Frequency
HP:0001660	Truncus arteriosus	Obligate (100%)
HP:0000961	Cyanosis	Very frequent (80-99%)
HP:0001627	Abnormal heart morphology	Very frequent (80-99%)
HP:0001649	Tachycardia	Very frequent (80-99%)
HP:0001654	Abnormal heart valve morphology	Very frequent (80-99%)
HP:0031653	Abnormal heart valve physiology	Very frequent (80-99%)
HP:0001511	Intrauterine growth retardation	Frequent (30-79%)
HP:0001629	Ventricular septal defect	Frequent (30-79%)
HP:0001640	Cardiomegaly	Frequent (30-79%)
HP:0001659	Aortic regurgitation	Frequent (30-79%)
HP:0001667	Right ventricular hypertrophy	Frequent (30-79%)
HP:0002789	Tachypnea	Frequent (30-79%)
HP:0011660	Anomalous origin of one pulmonary artery from ascending aorta	Frequent (30-79%)
HP:0012020	Right aortic arch	Frequent (30-79%)
HP:0000778	Hypoplasia of the thymus	Occasional (5-29%)
HP:0000849	Adrenocortical abnormality	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001636	Tetralogy of Fallot	Occasional (5-29%)
HP:0001642	Pulmonic stenosis	Occasional (5-29%)
HP:0001643	Patent ductus arteriosus	Occasional (5-29%)
HP:0001999	Abnormal facial shape	Occasional (5-29%)
HP:0002089	Pulmonary hypoplasia	Occasional (5-29%)
HP:0002101	Abnormal lung lobation	Occasional (5-29%)
HP:0004415	Pulmonary artery stenosis	Occasional (5-29%)
HP:0004935	Pulmonary artery atresia	Occasional (5-29%)
HP:0005301	Persistent left superior vena cava	Occasional (5-29%)
HP:0006704	Abnormal coronary artery morphology	Occasional (5-29%)
HP:0011611	Interrupted aortic arch	Occasional (5-29%)
HP:0011640	Single coronary artery origin	Occasional (5-29%)
HP:0025575	Abnormal superior vena cava morphology	Occasional (5-29%)
HP:0031014	Arteria lusoria	Occasional (5-29%)
HP:0045060	Aplasia/hypoplasia involving bones of the extremities	Occasional (5-29%)
HP:0100598	Pulmonary edema	Occasional (5-29%)
HP:0001669	Transposition of the great arteries	Very rare (<1-4%)
HP:0004971	Pulmonary artery hypoplasia	Very rare (<1-4%)
HP:0031635	Anomalous origin of the left common carotid artery from the brachiocephalic artery	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	persistent truncus arteriosus
Mondo ID	MONDO:0018072
MeSH	D014339
Orphanet	3384
ICD-10-CM	Q20.0
ICD-11	1832500366
NCIT	C98880
UMLS	C0041207
MedGen	52867
GARD	0016627
NORD	1800
Is cancer (heuristic)	no

Also known as: common aorticopulmonary trunk · common arterial trunk · common truncus arteriosus · persistent truncus arteriosus · persistent truncus arteriosus (disease) · TAC · Truncus Arteriosus · truncus arteriosus

Data availability: 5 ClinVar variants · 1 GenCC gene-disease record · 3 cell lines.

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 › persistent truncus arteriosus

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, 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, TFAP2B-related congenital heart disease spectrum disorder, PLD1-related congenital heart disease

Subtypes (2): common arterial trunk with aortic dominance, common arterial trunk with pulmonary dominance and interrupted aortic arch

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:

2 pathogenic, 1 benign/likely benign, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
30206	NM_005257.6(GATA6):c.1457_1458del (p.Glu486fs)	GATA6	Pathogenic	criteria provided, single submitter
30207	NM_005257.6(GATA6):c.1396A>C (p.Asn466His)	GATA6	Pathogenic	no assertion criteria provided
791	NM_001136271.3(NKX2-6):c.451T>C (p.Phe151Leu)	NKX2-6	Likely pathogenic	criteria provided, single submitter
9008	NM_004387.4(NKX2-5):c.73C>T (p.Arg25Cys)	NKX2-5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
129132	NM_005257.6(GATA6):c.969CCA[9] (p.His333del)	GATA6	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 24 · 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
PLXND1	Supportive	Autosomal recessive	persistent truncus arteriosus	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PLXND1	Orphanet:3384	Common arterial trunk
PLXND1	Orphanet:570	Moebius syndrome
NKX2-5	Orphanet:101351	Familial isolated congenital asplenia
NKX2-5	Orphanet:1479	Atrial septal defect-atrioventricular conduction defects syndrome
NKX2-5	Orphanet:1627	Deletion 5q35 syndrome
NKX2-5	Orphanet:2248	Hypoplastic left heart syndrome
NKX2-5	Orphanet:3303	Tetralogy of Fallot
NKX2-5	Orphanet:334	Hereditary atrial fibrillation
NKX2-5	Orphanet:402075	Familial bicuspid aortic valve
NKX2-5	Orphanet:871	Hereditary progressive cardiac conduction defect
NKX2-5	Orphanet:95712	Thyroid ectopia
NKX2-5	Orphanet:95713	Athyreosis
NKX2-5	Orphanet:99103	Atrial septal defect, ostium secundum type
NKX2-6	Orphanet:3303	Tetralogy of Fallot
NKX2-6	Orphanet:334	Hereditary atrial fibrillation
NKX2-6	Orphanet:3384	Common arterial trunk
GATA6	Orphanet:2140	Congenital diaphragmatic hernia
GATA6	Orphanet:2255	Pancreatic hypoplasia-diabetes-congenital heart disease syndrome
GATA6	Orphanet:3303	Tetralogy of Fallot
GATA6	Orphanet:334	Hereditary atrial fibrillation
GATA6	Orphanet:665044	Common arterial trunk with aortic dominance
GATA6	Orphanet:665058	Common arterial trunk with pulmonary dominance and interrupted aortic arch
GATA6	Orphanet:99067	Complete atrioventricular septal defect with ventricular hypoplasia
GATA6	Orphanet:99103	Atrial septal defect, ostium secundum type

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PLXND1	HGNC:9107	ENSG00000004399	Q9Y4D7	Plexin-D1	gencc
NKX2-5	HGNC:2488	ENSG00000183072	P52952	Homeobox protein Nkx-2.5	clinvar
NKX2-6	HGNC:32940	ENSG00000180053	A6NCS4	Homeobox protein Nkx-2.6	clinvar
GATA6	HGNC:4174	ENSG00000141448	Q92908	Transcription factor GATA-6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PLXND1	Plexin-D1	Cell surface receptor for SEMA4A and for class 3 semaphorins, such as SEMA3A, SEMA3C and SEMA3E.
NKX2-5	Homeobox protein Nkx-2.5	Transcription factor required for the development of the heart and the spleen.
NKX2-6	Homeobox protein Nkx-2.6	Acts as a transcriptional activator.
GATA6	Transcription factor GATA-6	Transcriptional activator.

Protein-family classification

Druggable: 1 · Difficult: 3 · Unknown: 0 · Druggable fraction: 0.25

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	3	6.2×	0.013
Antibody/Immunoglobulin	1	7.3×	0.130

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PLXND1	Antibody/Immunoglobulin	yes		Semap_dom, Plexin_repeat, IPT_dom
NKX2-5	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
NKX2-6	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
GATA6	Transcription factor	no		Znf_GATA, GATA_N, Znf_NHR/GATA

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)	1
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right atrium auricular region	2
right coronary artery	1
right lung	1
upper lobe of left lung	1
apex of heart	1
cardiac atrium	1
minor salivary gland	1
saliva-secreting gland	1
germinal epithelium of ovary	1
jejunal mucosa	1
parietal pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PLXND1	278	ubiquitous	marker	upper lobe of left lung, right coronary artery, right lung
NKX2-5	98	broad	yes	apex of heart, right atrium auricular region, cardiac atrium
NKX2-6	13	tissue_specific	yes	right atrium auricular region, minor salivary gland, saliva-secreting gland
GATA6	204	ubiquitous	marker	germinal epithelium of ovary, parietal pleura, jejunal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NKX2-5	2,355
PLXND1	1,454
NKX2-6	543
GATA6	49

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NKX2-5	P52952	4
PLXND1	Q9Y4D7	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NKX2-6	A6NCS4	64.31
GATA6	Q92908	53.48

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Cardiogenesis	2	282.0×	2e-04	NKX2-5, GATA6
POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation	1	380.7×	0.008	GATA6
YAP1- and WWTR1 (TAZ)-stimulated gene expression	1	253.8×	0.008	NKX2-5
Formation of definitive endoderm	1	237.9×	0.008	GATA6
Physiological factors	1	223.9×	0.008	NKX2-5
Other semaphorin interactions	1	200.3×	0.008	PLXND1
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	1	200.3×	0.008	GATA6
NOTCH3 Intracellular Domain Regulates Transcription	1	146.4×	0.009	PLXND1
Surfactant metabolism	1	122.8×	0.010	GATA6
RND2 GTPase cycle	1	86.5×	0.013	PLXND1
Factors involved in megakaryocyte development and platelet production	1	22.1×	0.045	GATA6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
atrial cardiac muscle cell development	2	2808.7×	2e-05	NKX2-5, NKX2-6
atrioventricular node development	2	1404.3×	3e-05	NKX2-5, GATA6
epithelial cell differentiation	3	131.7×	3e-05	NKX2-5, NKX2-6, GATA6
ventricular cardiac muscle cell development	2	766.0×	7e-05	NKX2-5, NKX2-6
negative regulation of epithelial cell apoptotic process	2	601.9×	1e-04	NKX2-5, NKX2-6
epithelial cell apoptotic process	2	421.3×	2e-04	NKX2-5, NKX2-6
pharyngeal system development	2	401.2×	2e-04	NKX2-5, NKX2-6
embryonic heart tube development	2	383.0×	2e-04	NKX2-5, NKX2-6
outflow tract septum morphogenesis	2	324.1×	2e-04	NKX2-5, GATA6
cardiac muscle cell proliferation	2	290.6×	2e-04	NKX2-5, GATA6
epithelial cell proliferation	2	156.0×	7e-04	NKX2-5, NKX2-6
positive regulation of epithelial cell proliferation	2	122.1×	1e-03	NKX2-5, NKX2-6
negative regulation of apoptotic process	3	26.1×	1e-03	NKX2-5, NKX2-6, GATA6
Purkinje myocyte differentiation	1	4213.0×	0.002	NKX2-5
septum secundum development	1	4213.0×	0.002	NKX2-5
negative regulation of transforming growth factor beta2 production	1	4213.0×	0.002	GATA6
tube morphogenesis	1	4213.0×	0.002	GATA6
negative regulation of sebum secreting cell proliferation	1	4213.0×	0.002	GATA6
regulation of antimicrobial humoral response	1	2106.5×	0.003	GATA6
right ventricular cardiac muscle tissue morphogenesis	1	2106.5×	0.003	NKX2-5
endodermal cell fate determination	1	2106.5×	0.003	GATA6
synaptic target recognition	1	2106.5×	0.003	PLXND1
atrioventricular node cell fate commitment	1	2106.5×	0.003	NKX2-5
sebaceous gland cell differentiation	1	1404.3×	0.003	GATA6
cardiac ventricle formation	1	1404.3×	0.003	NKX2-5
apoptotic process involved in heart morphogenesis	1	1404.3×	0.003	NKX2-5
proepicardium development	1	1404.3×	0.003	NKX2-5
pulmonary myocardium development	1	1404.3×	0.003	NKX2-5
ventricular cardiac myofibril assembly	1	1404.3×	0.003	NKX2-5
positive regulation of cardiac muscle myoblast proliferation	1	1404.3×	0.003	GATA6

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 4 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
PLXND1	0	0
NKX2-5	0	0
NKX2-6	0	0
GATA6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	1	PLXND1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	NKX2-5, NKX2-6, GATA6

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)
PLXND1	0	—
NKX2-5	0	—
NKX2-6	0	—
GATA6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05452720	Not specified	RECRUITING	MASA Valve Early Feasibility Study
NCT05809310	Not specified	RECRUITING	Effects Branch PA Stenting d-TGA, ToF and TA
NCT06768008	Not specified	RECRUITING	An Integrated Prenatal and Postnatal Treatment Model for the Treatment of Newborns With Critical Congenital Heart Disease
NCT06771687	Not specified	RECRUITING	High Intensity Interval Training in Patients With a Right Ventricle to Pulmonary Artery Conduit
NCT04452188	Not specified	COMPLETED	Targeting Normoxia in Neonates With Cyanotic Congenital Heart Disease in the Intra-operative and Immediate Post-operative Period
NCT04788082	Not specified	WITHDRAWN	Clinical Impact of Rapid Prototyping 3D Models for Surgical Management