Tricuspid atresia

Summary

Tricuspid atresia (MONDO:0011514) is a disease with 1 cohort gene and 10 clinical trials. Top therapeutic interventions include bosentan, sildenafil, and liothyronine i 131.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 2
• Phenotypes (HPO): 10
• Clinical trials: 10

Clinical features

Epidemiology

Prevalence records

19 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000		Europe	Validated
Prevalence at birth	1-9 / 100 000	5.5625	Europe	Validated
Prevalence at birth	1-9 / 100 000	5.9	Belgium	Validated
Prevalence at birth	1-9 / 100 000	9	France	Validated
Prevalence at birth	1-9 / 100 000	3	Germany	Validated
Prevalence at birth	1-5 / 10 000	10.5	Ireland	Validated
Prevalence at birth	1-9 / 100 000	6.5	Italy	Validated
Prevalence at birth	1-9 / 100 000	4	Netherlands	Validated
Prevalence at birth	1-9 / 100 000	3.3	Norway	Validated
Prevalence at birth	1-9 / 100 000	1.5	Poland	Validated
Prevalence at birth	1-9 / 100 000	1.9	Spain	Validated
Prevalence at birth	1-5 / 10 000	11.1	Portugal	Validated
Prevalence at birth	1-5 / 10 000	12.6	Switzerland	Validated
Prevalence at birth	1-9 / 100 000	5	United Kingdom	Validated
Prevalence at birth	1-9 / 100 000	9.7	Ukraine	Validated
Prevalence at birth	1-9 / 100 000	4.6	Taiwan, Province of China	Validated
Prevalence at birth	1-9 / 100 000	8	Malta	Validated
Prevalence at birth	1-9 / 100 000	6	Czech Republic	Validated
Prevalence at birth	1-9 / 100 000	3	Slovakia	Validated

Signs & symptoms

Clinical features (HPO)

10 HPO clinical features (Orphanet curated; top 10 by frequency):

HPO ID	Term	Frequency
HP:0011662	Tricuspid atresia	Obligate (100%)
HP:0000961	Cyanosis	Very frequent (80-99%)
HP:0001629	Ventricular septal defect	Very frequent (80-99%)
HP:0001631	Atrial septal defect	Frequent (30-79%)
HP:0001655	Patent foramen ovale	Frequent (30-79%)
HP:0001669	Transposition of the great arteries	Frequent (30-79%)
HP:0004762	Hypoplasia of right ventricle	Frequent (30-79%)
HP:0005301	Persistent left superior vena cava	Frequent (30-79%)
HP:0001680	Coarctation of aorta	Occasional (5-29%)
HP:0004935	Pulmonary artery atresia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	tricuspid atresia
Mondo ID	MONDO:0011514
MeSH	D018785
OMIM	605067
Orphanet	1209
DOID	DOID:0080169
ICD-11	845891723
NCIT	C85202
SNOMED CT	63042009
UMLS	C0243002
MedGen	67034
GARD	0005274
MedDRA	10049767
Is cancer (heuristic)	no

Also known as: congenital agenesis of the tricuspid valve · congenital atresia of tricuspid valve · tricuspid atresia · tricuspid atresia (disease) · tricuspid valve atresia

Data availability: 2 ClinVar variants · 1 HPO phenotype · 9 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › congenital heart disease › tricuspid atresia

Related subtypes (22): congenital heart defects, multiple types, heart septal defect, tetralogy of fallot, heart defects-limb shortening syndrome, 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, TFAP2B-related congenital heart disease spectrum disorder, PLD1-related congenital heart disease

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

2 retrieved; paginated sample, class counts are floors:

2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
816915	NM_002332.3(LRP1):c.1576C>G (p.Leu526Val)	LRP1	Uncertain significance	criteria provided, single submitter
816916	NM_002332.3(LRP1):c.13559C>G (p.Ser4520Cys)	LRP1	Uncertain significance	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
LRP1	Orphanet:2340	Keratosis follicularis spinulosa decalvans
LRP1	Orphanet:79100	Atrophoderma vermiculata

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
LRP1	HGNC:6692	ENSG00000123384	Q07954	Prolow-density lipoprotein receptor-related protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LRP1	Prolow-density lipoprotein receptor-related protein 1	Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells.

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)
LRP1	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF

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
ascending aorta	1
descending thoracic aorta	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LRP1	293	ubiquitous	marker	stromal cell of endometrium, descending thoracic aorta, ascending aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LRP1	2,662

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LRP1	Q07954	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
Scavenging of heme from plasma	1	878.5×	0.007	LRP1
Binding and Uptake of Ligands by Scavenger Receptors	1	543.8×	0.007	LRP1
Metabolism of fat-soluble vitamins	1	380.7×	0.007	LRP1
Visual phototransduction	1	259.6×	0.007	LRP1
Retinoid metabolism and transport	1	248.3×	0.007	LRP1
Metabolism of vitamins and cofactors	1	116.5×	0.013	LRP1
Sensory Perception	1	95.2×	0.014	LRP1
Vesicle-mediated transport	1	34.8×	0.032	LRP1
Metabolism	1	11.6×	0.086	LRP1

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
positive regulation of transcytosis	1	16852.0×	0.001	LRP1
positive regulation of lipid transport	1	8426.0×	0.001	LRP1
positive regulation of reverse cholesterol transport	1	8426.0×	0.001	LRP1
astrocyte activation involved in immune response	1	4213.0×	0.001	LRP1
negative regulation of platelet-derived growth factor receptor-beta signaling pathway	1	4213.0×	0.001	LRP1
regulation of extracellular matrix disassembly	1	3370.4×	0.001	LRP1
positive regulation of lysosomal protein catabolic process	1	3370.4×	0.001	LRP1
amyloid-beta clearance by transcytosis	1	2407.4×	0.002	LRP1
amyloid-beta clearance by cellular catabolic process	1	2106.5×	0.002	LRP1
positive regulation of amyloid-beta clearance	1	2106.5×	0.002	LRP1
regulation of extracellular matrix organization	1	1872.4×	0.002	LRP1
transcytosis	1	1685.2×	0.002	LRP1
negative regulation of smooth muscle cell migration	1	1532.0×	0.002	LRP1
enzyme-linked receptor protein signaling pathway	1	1296.3×	0.002	LRP1
lipoprotein transport	1	991.3×	0.002	LRP1
amyloid-beta clearance	1	936.2×	0.002	LRP1
aorta morphogenesis	1	887.0×	0.002	LRP1
apoptotic cell clearance	1	887.0×	0.002	LRP1
positive regulation of endocytosis	1	802.5×	0.002	LRP1
lysosomal transport	1	702.2×	0.002	LRP1
positive regulation of cholesterol efflux	1	624.1×	0.002	LRP1
negative regulation of SMAD protein signal transduction	1	601.9×	0.002	LRP1
retinoid metabolic process	1	495.6×	0.003	LRP1
cellular response to amyloid-beta	1	391.9×	0.004	LRP1
negative regulation of Wnt signaling pathway	1	343.9×	0.004	LRP1
receptor internalization	1	324.1×	0.004	LRP1
positive regulation of protein localization to plasma membrane	1	271.8×	0.004	LRP1
phagocytosis	1	240.7×	0.005	LRP1
receptor-mediated endocytosis	1	221.7×	0.005	LRP1
transport across blood-brain barrier	1	179.3×	0.006	LRP1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LRP1	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	LRP1

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)
LRP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 10.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE2	3
PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04467671	PHASE2	RECRUITING	Two-Year Study of the Safety and Efficacy of the Second-Generation Tissue Engineered Vascular Grafts
NCT00507819	PHASE2	COMPLETED	Sildenafil After the Fontan Operation
NCT01292551	PHASE2	COMPLETED	Study of Placebo or Bosentan to Treat Patients With Single Ventricle Physiology.
NCT00004828	PHASE1	COMPLETED	Liothyronine in Children With Single Ventricle Congenital Cardiac Malformations Undergoing the Fontan Procedure
NCT00573066	PHASE1	COMPLETED	Understanding Dexmedetomidine In Infants Post-Operative From Cardiac Surgery
NCT04106479	Not specified	RECRUITING	NIRS in Congenital Heart Defects - Correlation With Echocardiography
NCT00571233	Not specified	COMPLETED	Biomarker Study for Heart Failure in Children With Single Ventricle Physiology
NCT00974025	Not specified	COMPLETED	Impact of Vitamin C on Endothelial Function and Exercise Capacity in Fontan-Palliated Patients
NCT01107990	Not specified	TERMINATED	Global and Regional Myocardial Strain and Power Output In Patients With Single Ventricles Using Novel MRI Techniques
NCT04176458	Not specified	TERMINATED	Methacetin Breath Test in Patients With Liver Disease Secondary to Heart Disease

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BOSENTAN	4	1
SILDENAFIL	4	1
LIOTHYRONINE I 131	1	1