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Atlas / Disease / Tricuspid valve insufficiency

Tricuspid valve insufficiency

disease
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Also known as insufficiency, tricuspidtricuspid insufficiencytricuspid valve regurgitation

Summary

Tricuspid valve insufficiency (MONDO:0002870) is a disease with 3 cohort genes and 64 clinical trials.

At a glance

  • Cohort genes: 3
  • ClinVar variants: 5
  • Clinical trials: 64

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nametricuspid valve insufficiency
Mondo IDMONDO:0002870
MeSHD014262
DOIDDOID:4080
ICD-11770887951
NCITC50842
SNOMED CT111287006
UMLSC0040961
MedGen11911
Anatomy (UBERON)UBERON:0002134
Is cancer (heuristic)no

Also known as: insufficiency, tricuspid · tricuspid insufficiency · tricuspid valve regurgitation

Data availability: 5 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › heart valve disorder › tricuspid valve disorder › tricuspid valve insufficiency

Related subtypes (3): tricuspid valve stenosis, congenital tricuspid malformation, cleft leaflet of tricuspid valve

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 uncertain significance, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVarVariant (HGVS)GeneClassificationReview
26785146;XX;ins(5;6)(p13;p24p25)dnPathogeniccriteria provided, single submitter
13329NM_002834.5(PTPN11):c.184T>G (p.Tyr62Asp)PTPN11Pathogenicreviewed by expert panel
374162NM_002474.3(MYH11):c.4360G>C (p.Asp1454His)MYH11Likely pathogeniccriteria provided, single submitter
9034NM_001308093.3(GATA4):c.1276G>A (p.Asp426Asn)GATA4Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
26788946;XX;inv(14)(q24.1q32.1)dnUncertain significancecriteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 16 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
GATA4Orphanet:2510718p23.1 microdeletion syndrome
GATA4Orphanet:25151046,XY partial gonadal dysgenesis
GATA4Orphanet:3303Tetralogy of Fallot
GATA4Orphanet:334Hereditary atrial fibrillation
GATA4Orphanet:576232Partial atrioventricular septal defect with ventricular hypoplasia
GATA4Orphanet:99067Complete atrioventricular septal defect with ventricular hypoplasia
GATA4Orphanet:99068Complete atrioventricular septal defect-tetralogy of Fallot
GATA4Orphanet:99103Atrial septal defect, ostium secundum type
MYH11Orphanet:2241Megacystis-microcolon-intestinal hypoperistalsis syndrome
MYH11Orphanet:229Familial aortic dissection
MYH11Orphanet:91387Familial thoracic aortic aneurysm and aortic dissection
MYH11Orphanet:98829Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)
PTPN11Orphanet:2499Metachondromatosis
PTPN11Orphanet:500Noonan syndrome with multiple lentigines
PTPN11Orphanet:648Noonan syndrome
PTPN11Orphanet:86834Juvenile myelomonocytic leukemia

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence3

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
GATA4HGNC:4173ENSG00000136574P43694Transcription factor GATA-4clinvar
MYH11HGNC:7569ENSG00000133392P35749Myosin-11clinvar
PTPN11HGNC:9644ENSG00000179295Q06124Tyrosine-protein phosphatase non-receptor type 11clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
GATA4Transcription factor GATA-4Transcriptional activator that binds to the consensus sequence 5’-AGATAG-3’ and plays a key role in cardiac development and function.
MYH11Myosin-11Muscle contraction.
PTPN11Tyrosine-protein phosphatase non-receptor type 11Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus.

Protein-family classification

Druggable: 1 · Difficult: 2 · Unknown: 0 · Druggable fraction: 0.33

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.

FamilyGenesFoldFDR
Phosphatase128.0×0.106
Scaffold/PPI15.8×0.246
Transcription factor12.8×0.321

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
GATA4Transcription factornoZnf_GATA, GATA_N, Znf_NHR/GATA
MYH11Scaffold/PPInoIQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail
PTPN11Phosphataseyes3.1.3.48PTP_cat, Tyr_Pase_dom, SH2

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)3
unknown0

Top tissues across cohort

TissueCohort genes
duodenum1
heart left ventricle1
right atrium auricular region1
lower esophagus1
lower esophagus muscularis layer1
right coronary artery1
dorsal motor nucleus of vagus nerve1
globus pallidus1
medial globus pallidus1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
GATA485broadmarkerright atrium auricular region, heart left ventricle, duodenum
MYH11143broadmarkerright coronary artery, lower esophagus, lower esophagus muscularis layer
PTPN11295ubiquitousmarkermedial globus pallidus, dorsal motor nucleus of vagus nerve, globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
PTPN116,009
GATA44,994
MYH113,818

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
PTPN11Q06124115
GATA4P436943
MYH11P357491

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 82. Enrichment computed across 3 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.

PathwayCohort genesFoldFDRSample cohort genes
MET activates PTPN111761.3×0.011PTPN11
Formation of lateral plate mesoderm1761.3×0.011GATA4
Co-inhibition by BTLA1761.3×0.011PTPN11
STAT5 Activation1543.8×0.011PTPN11
Netrin mediated repulsion signals1423.0×0.011PTPN11
MAPK1 (ERK2) activation1380.7×0.011PTPN11
STAT5 activation downstream of FLT3 ITD mutants1380.7×0.011PTPN11
MAPK3 (ERK1) activation1346.1×0.011PTPN11
Signaling by Leptin1346.1×0.011PTPN11
Interleukin-6 signaling1317.2×0.011PTPN11
Activated NTRK2 signals through FRS2 and FRS31317.2×0.011PTPN11
PECAM1 interactions1292.8×0.011PTPN11
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)1292.8×0.011GATA4
Regulation of IFNG signaling1271.9×0.011PTPN11
Prolactin receptor signaling1253.8×0.011PTPN11
YAP1- and WWTR1 (TAZ)-stimulated gene expression1253.8×0.011GATA4
Signaling by FLT3 ITD and TKD mutants1253.8×0.011PTPN11
Spry regulation of FGF signaling1237.9×0.011PTPN11
Transcriptional regulation of testis differentiation1237.9×0.011GATA4
Formation of definitive endoderm1237.9×0.011GATA4
Signal regulatory protein family interactions1223.9×0.011PTPN11
Sema4D in semaphorin signaling1223.9×0.011MYH11
Platelet sensitization by LDL1223.9×0.011PTPN11
Physiological factors1223.9×0.011GATA4
Regulation of RUNX1 Expression and Activity1223.9×0.011PTPN11
GAB1 signalosome1211.5×0.011PTPN11
PI-3K cascade:FGFR31211.5×0.011PTPN11
Tie2 Signaling1200.3×0.011PTPN11
RHO GTPases activate CIT1200.3×0.011MYH11
RHO GTPases Activate ROCKs1200.3×0.011MYH11

GO biological processes 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.

GO termCohort genesFoldFDRSample cohort genes
atrioventricular canal development21021.3×1e-04GATA4, PTPN11
negative regulation of cortisol secretion15617.3×0.006PTPN11
negative regulation of growth hormone secretion15617.3×0.006PTPN11
atrial septum secundum morphogenesis12808.7×0.006GATA4
microvillus organization12808.7×0.006PTPN11
intestinal epithelial cell migration12808.7×0.006PTPN11
cerebellar cortex formation11872.4×0.006PTPN11
skeletal muscle myosin thick filament assembly11872.4×0.006MYH11
embryonic heart tube anterior/posterior pattern specification11872.4×0.006GATA4
atrioventricular valve formation11404.3×0.006GATA4
regulation of type I interferon-mediated signaling pathway11404.3×0.006PTPN11
cardiac muscle tissue regeneration11404.3×0.006GATA4
atrial septum primum morphogenesis11123.5×0.006GATA4
ERBB signaling pathway11123.5×0.006PTPN11
atrioventricular node development1936.2×0.007GATA4
cell growth involved in cardiac muscle cell development1802.5×0.007GATA4
negative regulation of neutrophil activation1802.5×0.007PTPN11
transdifferentiation1702.2×0.007GATA4
cardiac ventricle morphogenesis1624.1×0.007GATA4
positive regulation of hormone secretion1561.7×0.007PTPN11
embryonic foregut morphogenesis1561.7×0.007GATA4
genitalia development1561.7×0.007PTPN11
positive regulation of lipopolysaccharide-mediated signaling pathway1510.7×0.007PTPN11
regulation of protein export from nucleus1510.7×0.007PTPN11
elastic fiber assembly1510.7×0.007MYH11
Bergmann glial cell differentiation1510.7×0.007PTPN11
intestinal epithelial cell differentiation1510.7×0.007GATA4
endocardial cushion development1468.1×0.007GATA4
cardiac right ventricle morphogenesis1468.1×0.007GATA4
negative regulation of cell adhesion mediated by integrin1432.1×0.008PTPN11

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

SymbolExample approved molecule
PTPN11ESTRAMUSTINE PHOSPHATE

Top cohort targets by molecule count

SymbolMoleculesMax phase
PTPN1184
GATA400
MYH1100

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
ESTRAMUSTINE PHOSPHATE4PTPN11
ENOXOLONE2PTPN11
CEFSULODIN2PTPN11
BATOPROTAFIB2PTPN11
VOCIPROTAFIB2PTPN11
JAB-30681PTPN11
PF-072848921PTPN11
BBP-3981PTPN11

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

SymbolAssaysType breakdown
PTPN11588Binding:585, Functional:2, ADMET:1
GATA45Binding:5

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
PTPN113.1.3.48protein-tyrosine-phosphatase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

SymbolChEMBL assays
PTPN11588

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

8 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.

CompoundMax phaseCohort target (bioactivity)
ESTRAMUSTINE PHOSPHATE4PTPN11
ENOXOLONE2PTPN11
CEFSULODIN2PTPN11
BATOPROTAFIB2PTPN11
VOCIPROTAFIB2PTPN11
JAB-30681PTPN11
PF-072848921PTPN11
BBP-3981PTPN11

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1PTPN11
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug2GATA4, MYH11

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

SymbolChEMBL assaysDrugged partners (top 3)
GATA45—
MYH110—

Clinical trials & evidence

Clinical trials

Clinical trials: 64.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified64

Top trials by phase / activity

NCTPhaseStatusTitle
NCT03779490Not specifiedACTIVE_NOT_RECRUITINGTranscatheter Repair of Tricuspid Regurgitation With Edwards Cardioband TR System Post Market Study (TriBAND)
NCT04097145Not specifiedRECRUITINGEdwards PASCAL Transcatheter Valve Repair System Pivotal Clinical Trial
NCT04221490Not specifiedACTIVE_NOT_RECRUITING2019-06 TRISCEND Study
NCT04436653Not specifiedRECRUITINGTHE TRAVEL TRIAL: Transcatheter Right Atrial-ventricular Valve rEplacement With LuX-Valve
NCT04482062Not specifiedACTIVE_NOT_RECRUITINGTRISCEND II Pivotal Trial
NCT04483089Not specifiedACTIVE_NOT_RECRUITINGAn Observational Real-world Study Evaluating Severe Tricuspid Regurgitation Patients Treated With the Abbott TriClip™ Device (bRIGHT)
NCT04577248Not specifiedRECRUITINGThe Prospecive OBSERVational Munich Interventional MITRAl-Valve Registry
NCT04614402Not specifiedACTIVE_NOT_RECRUITINGTranscatheter Repair of Tricuspid Regurgitation With Edwards PASCAL Transcatheter Valve Repair System
NCT04653428Not specifiedRECRUITINGGerman Registry for Transcatheter Tricuspid Valve Interventions
NCT04735003Not specifiedRECRUITINGTranscatheter Interventions for Tricuspid Insufficiency in Italy
NCT05114850Not specifiedRECRUITINGRetrospective Prospective Multicentric Clinical Follow up of Patients After Being Treated With TricValve®
NCT05194423Not specifiedRECRUITINGTHE TRAVEL II TRIAL: Transcatheter Right Atrial-ventricular Valve rEplacement With LuX-Valve Via Jugular Vein
NCT05577078Not specifiedNOT_YET_RECRUITINGTriBEL Registry: National Belgian Registry of Percutaneous Tricuspid Valve Repair Using a Transcatheter Edge-to-edge Repair Technique
NCT05742906Not specifiedRECRUITINGCorMatrix Cor TRICUSPID ECM Valve Replacement - Pivotal Study
NCT05760989Not specifiedACTIVE_NOT_RECRUITINGTRISCEND JAPAN Study
NCT05820516Not specifiedRECRUITINGPatients With Severe TrIcuspid Regurgitation After triCvALve System Implantation
NCT05913908Not specifiedRECRUITINGEFS of the DUO System for Tricuspid Regurgitation
NCT06196684Not specifiedACTIVE_NOT_RECRUITINGEarly Safety and Clinical Efficacy of Mitral Allograft in Tricuspid Surgery
NCT06235385Not specifiedRECRUITINGEuropean Association of Cardiovascular Imaging Multiple and Mixed Valvular Disease Study
NCT06377449Not specifiedRECRUITINGInfluence of Lung Ultrasonography on the Prognosis and Postoperative Outcomes in Cardiac Surgical Patients
NCT06458907Not specifiedNOT_YET_RECRUITINGPivotal Trial to Evaluate the Safety and Effectiveness of the P&F TricValve® Transcatheter Bicaval Valve System
NCT06506942Not specifiedRECRUITINGThe TRICURE EFS Study
NCT06569602Not specifiedRECRUITINGReal World European Investigation of Safety and Clinical Efficacy of the EVOQUE System (TRISCEND III EU)
NCT06581471Not specifiedRECRUITINGThe TRICURE EU Pivotal Study
NCT06611579Not specifiedRECRUITINGClinical Study of the inQB8 TTVR System (The MonarQ Study)
NCT06700239Not specifiedNOT_YET_RECRUITINGThe STTAR-US Study: A Pivotal Study of Transcatheter Tricuspid Annular Repair in the US
NCT07068633Not specifiedNOT_YET_RECRUITINGKorea VHD Echo Study: Surveillance of Aortic, Mitral & Tricuspid Patients - Insights From Real-world Practice
NCT07267117Not specifiedRECRUITINGCohort Observing Mechanisms, Progression and Sequelae of Valvular Heart Disease
NCT07342036Not specifiedRECRUITINGProspective Study of Lead-associated Tricuspid Regurgitation in Patients Undergoing New Transvalvular Lead Insertion
NCT07464106Not specifiedRECRUITINGEvaluation of the Impact of Interventional Treatments for Symptomatic, Severe Tricuspid Valve Insufficiency on Renal Integrity and Function, as Well as on Physical Function and Activity in Older Adults.
NCT07516444Not specifiedNOT_YET_RECRUITINGVDyne Transcatheter Tricuspid Valve Replacement Study to Evaluate Safety and Clinical Efficacy in Patients With Symptomatic Severe Tricuspid Valve Regurgitation (TRIVITA Pivotal Trial)
NCT07578129Not specifiedNOT_YET_RECRUITINGPASCAL Precision-GDMT Registry
NCT01246141Not specifiedCOMPLETEDThe Comparison of Tricuspid Replacement and Repair in Patients With Combined Heart Valve Disease
NCT01246947Not specifiedCOMPLETEDTricuspid Annuloplasty for Moderate Tricuspid Regurgitation Associated With Miral Operation
NCT01334801Not specifiedCOMPLETEDBiomarkers in Aortic Stenosis - B.A.S.S.
NCT01444222Not specifiedCOMPLETEDBehaviour of Tricuspid Valve Regurgitation in Volume and/or Pressure Loaded Right Heart
NCT01532921Not specifiedCOMPLETEDEASE TRICUSPID Expertise-based Assessment Study on Clinical Efficacy of Contour 3D® in TRICUSPID Valve Annuloplasty
NCT01537458Not specifiedCOMPLETEDLong-term Outcome After Isolated Tricuspid Valve Repair
NCT01580436Not specifiedUNKNOWNProphylactic Tricuspid Valve Annuloplasty in Patients Undergoing Mitral Valve Surgery
NCT01585779Not specifiedCOMPLETEDContour 3D®/TriAd® Tricuspid Annuloplasty Ring Post-Market Clinical Trial

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

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This page pulls from 72 datasets indexed by BioBTree:

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