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Atlas / Disease / Chagas cardiomyopathy

Chagas cardiomyopathy

disease
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Also known as Trypanosoma cruzi cardiomyopathyTrypanosoma cruzi caused cardiomyopathy

Summary

Chagas cardiomyopathy (MONDO:0005491) is a disease with 3 cohort genes (32 GWAS associations across 3 studies) and 16 clinical trials. Top therapeutic interventions include bisoprolol, enalapril, and amiodarone hydrochloride.

At a glance

  • Cohort genes: 3
  • GWAS associations: 32
  • Clinical trials: 16

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameChagas cardiomyopathy
Mondo IDMONDO:0005491
EFOEFO:0005529
MeSHD002598
SNOMED CT998008
UMLSC0007930
MedGen868
GARD0024193
Is cancer (heuristic)no

Also known as: Trypanosoma cruzi cardiomyopathy · Trypanosoma cruzi caused cardiomyopathy

Data availability: 32 GWAS associations (3 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › Chagas cardiomyopathy

Related subtypes (11): Keshan disease, intrinsic cardiomyopathy, extrinsic cardiomyopathy, idiopathic cardiomyopathy, familial cardiomyopathy, non-compaction cardiomyopathy, Uhl anomaly, Tako-tsubo cardiomyopathy, cardiomyopathy due to anthracyclines, doxorubicin induced cardiomyopathy, autoimmune cardiomyopathy

Genetics & variants

GWAS landscape

32 GWAS associations across 3 studies. Top hits map to 22 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs24582983e-08NAALADL1G0.9
rs625599103e-08ANKRD18B, CYP4F26PT1.6
rs342381874e-08PPIAP14 - LINC01892G0.37
rs1156565807e-08NPR3 - LINC02120G0.31
rs41490181e-07SLCO1B1?
rs1154449782e-07SIGLEC8G0.34
rs27644723e-07PSMC1P12 - TBX15T0.7
rs110207513e-07IZUMO1R - GPR83T0.46
rs107592405e-07RNU6-492P - KLF4C0.92
rs115864466e-07RIIAD1 - RNU6-662PG0.55
rs1168006296e-07IPCEF1T0.4
rs2872283718e-07C0.72
rs169779998e-07AGBL1G0.3
rs104721569e-07LINC02100A1.1
rs123191131e-06CAPZA3 - RPL7P6?
rs1825033381e-06ILRUN?
rs171106311e-06DIO2-AS1G0.44
rs359558413e-06SPTB?
rs78299874e-06PDGFRL?
rs125427434e-06NRG1?
rs22629094e-06ZNF208?
rs44933634e-06ACO2P1 - LINC02885?
rs104680924e-06LINC02895?
rs24800544e-06KAZN?
rs69102334e-06Metazoa_SRP - BAK1?
rs101327605e-06TRAV3 - TRAV4?
rs783563565e-06MITF?
rs351310646e-06CAPN11 - RN7SL811P?
rs107697836e-06SYT9?
rs731995257e-06TIAM1?

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90104564Sabino EC20222,3830Genome-wide association study for Chagas Cardiomyopathy identify a new risk locus on chromosome 18 associated with an immune-related protein and transcriptional signature.
GCST90026454Casares-Marfil D20219811,328A genome-wide association study identifies novel susceptibility loci in chronic Chagas cardiomyopathy.
GCST002285Deng X20132070Genome wide association study (GWAS) of Chagas cardiomyopathy in Trypanosoma cruzi seropositive subjects.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding1
Tier 2: splice/UTR0
Tier 3: regulatory1
Tier 4: intronic/intergenic30

MAF distribution

BucketVariants
common (>=0.05)28
low_freq (0.01-0.05)0
rare (<0.01)0
unknown4

Functional consequences

ConsequenceCount
intron_variant20
intergenic_variant8
regulatory_region_variant1
unknown1
non_coding_transcript_exon_variant1
missense_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs24582981165047341T>G0.26intron_variantNAALADL13e-08Tier 4: intronic/intergenic
rs62559910933594707G>A,T0.05intron_variantANKRD18B, CYP4F26P3e-08Tier 4: intronic/intergenic
rs34238187185052220C>G,T0.05intron_variantPPIAP14 - LINC018924e-08Tier 4: intronic/intergenic
rs115656580532862370A>Gintron_variantNPR3 - LINC021207e-08Tier 4: intronic/intergenic
rs41490181221138627T>G0.05intron_variantSLCO1B11e-07Tier 4: intronic/intergenic
rs1154449781951454137A>Gintron_variantSIGLEC82e-07Tier 4: intronic/intergenic
rs27644721118760136T>A,C,G0.05intergenic_variantPSMC1P12 - TBX153e-07Tier 4: intronic/intergenic
rs110207511194370564C>G,T0.05intergenic_variantIZUMO1R - GPR833e-07Tier 4: intronic/intergenic
rs107592409107479876A>C0.46intron_variantRNU6-492P - KLF45e-07Tier 4: intronic/intergenic
rs115864461151740012A>G0.05regulatory_region_variantRIIAD1 - RNU6-662P6e-07Tier 3: regulatory
rs1168006296154277027C>T0.05intron_variantIPCEF16e-07Tier 4: intronic/intergenic
rs2872283718e-07Tier 4: intronic/intergenic
rs169779991586802711C>Gintron_variantAGBL18e-07Tier 4: intronic/intergenic
rs10472156518718887C>A,G,T0.27intron_variantLINC021009e-07Tier 4: intronic/intergenic
rs123191131218871624G>A,C,T0.05intergenic_variantCAPZA3 - RPL7P61e-06Tier 4: intronic/intergenic
rs182503338634614497T>G0.05intron_variantILRUN1e-06Tier 4: intronic/intergenic
rs171106311480411016T>G0.05intron_variantDIO2-AS11e-06Tier 4: intronic/intergenic
rs359558411464852643G>A0.05intron_variantSPTB3e-06Tier 4: intronic/intergenic
rs7829987817604713T>G0.05non_coding_transcript_exon_variantPDGFRL4e-06Tier 4: intronic/intergenic
rs12542743832460839T>C0.05intron_variantNRG14e-06Tier 4: intronic/intergenic
rs22629091921952468A>C0.05intergenic_variantZNF2084e-06Tier 4: intronic/intergenic
rs44933632234748420G>A0.05intergenic_variantACO2P1 - LINC028854e-06Tier 4: intronic/intergenic
rs104680921538142690A>C,G,T0.05intergenic_variantLINC028954e-06Tier 4: intronic/intergenic
rs2480054114466039A>G,T0.05intron_variantKAZN4e-06Tier 4: intronic/intergenic
rs6910233633566949G>A,T0.05intron_variantMetazoa_SRP - BAK14e-06Tier 4: intronic/intergenic
rs101327601421728267C>A,G,T0.05intergenic_variantTRAV3 - TRAV45e-06Tier 4: intronic/intergenic
rs78356356369774942A>G0.05intron_variantMITF5e-06Tier 4: intronic/intergenic
rs35131064644204326C>T0.05intergenic_variantCAPN11 - RN7SL811P6e-06Tier 4: intronic/intergenic
rs10769783117374960A>G,T0.05intron_variantSYT96e-06Tier 4: intronic/intergenic
rs731995252131512535G>A,T0.05intron_variantTIAM17e-06Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SLCO1B1Orphanet:3111Rotor syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only3

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SLCO1B1HGNC:10959ENSG00000134538Q9Y6L6Solute carrier organic anion transporter family member 1B1gwas
SYT9HGNC:19265ENSG00000170743Q86SS6Synaptotagmin-9gwas
ILRUNHGNC:21215ENSG00000196821Q9H6K1Protein ILRUNgwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SLCO1B1Solute carrier organic anion transporter family member 1B1Mediates the Na(+)-independent uptake of organic anions.
SYT9Synaptotagmin-9May be involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain or may serve as Ca(2+) sensors in the process of vesicular trafficking and exocytosis.
ILRUNProtein ILRUNNegative regulator of innate antiviral response.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

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
Transporter125.9×0.114
Antibody/Immunoglobulin19.7×0.149
Other/Unknown10.6×0.914

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SLCO1B1TransporteryesKazal_dom, OATP, MFS_dom
SYT9Other/UnknownnoC2_dom, Synaptotagmin, C2_domain_sf
ILRUNAntibody/ImmunoglobulinyesUBA-like_sf, Ig-like_fold, Nbr1_FW

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)

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

Top tissues across cohort

TissueCohort genes
liver1
male germ line stem cell (sensu Vertebrata) in testis1
right lobe of liver1
cerebellar vermis1
globus pallidus1
medial globus pallidus1
gastrocnemius1
muscle of leg1
tendon of biceps brachii1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SLCO1B129tissue_specificmarkerright lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
SYT9153broadyesmedial globus pallidus, globus pallidus, cerebellar vermis
ILRUN290ubiquitousmarkergastrocnemius, tendon of biceps brachii, muscle of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
SLCO1B11,380
SYT9800
ILRUN599

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
SLCO1B1Q9Y6L69
ILRUNQ9H6K11

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
SYT9Q86SS675.27

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Defective SLCO1B1 causes hyperbilirubinemia, Rotor type (HBLRR)15710.0×0.004SLCO1B1
Metabolism of porphyrins1713.8×0.011SLCO1B1
Atorvastatin ADME1713.8×0.011SLCO1B1
Organic anion transport by SLCO transporters1519.1×0.012SLCO1B1
Heme degradation1407.9×0.012SLCO1B1
Recycling of bile acids and salts1300.5×0.013SLCO1B1
Bile acid and bile salt metabolism1248.3×0.014SLCO1B1
Transport of vitamins, nucleosides, and related molecules1135.9×0.020SLCO1B1
Protein-protein interactions at synapses1132.8×0.020SYT9
Drug ADME1114.2×0.020SLCO1B1
SLC transporter disorders1102.0×0.020SLCO1B1
Neurexins and neuroligins198.5×0.020SYT9
Disorders of transmembrane transporters169.6×0.025SLCO1B1
Metabolism of steroids168.8×0.025SLCO1B1
Cargo recognition for clathrin-mediated endocytosis152.4×0.030SYT9
Clathrin-mediated endocytosis142.6×0.035SYT9
SLC-mediated transmembrane transport129.6×0.047SLCO1B1
Neuronal System122.1×0.060SYT9
Membrane Trafficking118.5×0.067SYT9
Vesicle-mediated transport117.4×0.068SYT9
Metabolism of lipids115.8×0.071SLCO1B1
Transport of small molecules112.6×0.085SLCO1B1
Disease16.5×0.153SLCO1B1
Metabolism15.8×0.165SLCO1B1

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
positive regulation of vesicle fusion1936.2×0.007SYT9
heme catabolic process1510.7×0.007SLCO1B1
negative regulation of defense response to virus1432.1×0.007ILRUN
calcium-dependent activation of synaptic vesicle fusion1432.1×0.007SYT9
sodium-independent organic anion transport1374.5×0.007SLCO1B1
negative regulation of DNA binding1374.5×0.007ILRUN
regulation of calcium ion-dependent exocytosis1312.1×0.007SYT9
negative regulation of protein localization to nucleus1280.9×0.007ILRUN
obsolete organic anion transport1267.5×0.007SLCO1B1
bile acid and bile salt transport1216.1×0.008SLCO1B1
negative regulation of type I interferon production1165.2×0.010ILRUN
negative regulation of tumor necrosis factor production183.8×0.017ILRUN
macroautophagy180.2×0.017ILRUN
monoatomic ion transport152.0×0.024SLCO1B1
xenobiotic metabolic process149.7×0.024SLCO1B1
vesicle-mediated transport132.1×0.035SYT9
chemical synaptic transmission125.8×0.041SYT9
innate immune response111.2×0.087ILRUN

Therapeutics

Drugs indicated for this disease

0 approved, 4 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
EnalaprilPhase 3 (in late-stage trials)
FilgrastimPhase 3 (in late-stage trials)
SacubitrilPhase 3 (in late-stage trials)
ValsartanPhase 3 (in late-stage trials)

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
SLCO1B1CANDESARTAN CILEXETIL

Top cohort targets by molecule count

SymbolMoleculesMax phase
SLCO1B1574
SYT900
ILRUN00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
CANDESARTAN CILEXETIL4SLCO1B1
TELMISARTAN4SLCO1B1
SIMVASTATIN4SLCO1B1
TELITHROMYCIN4SLCO1B1
PRAVASTATIN4SLCO1B1
MOMETASONE FUROATE4SLCO1B1
ATAZANAVIR4SLCO1B1
HYDROXYZINE PAMOATE4SLCO1B1
ERYTHROMYCIN ETHYLSUCCINATE4SLCO1B1
OLMESARTAN MEDOXOMIL4SLCO1B1
DICLOXACILLIN SODIUM4SLCO1B1
BETA CAROTENE4SLCO1B1
NONOXYNOL 94SLCO1B1
ATORVASTATIN4SLCO1B1
VINBLASTINE4SLCO1B1
CYCLOSPORINE4SLCO1B1
RITONAVIR4SLCO1B1
CARBENOXOLONE SODIUM4SLCO1B1
CLARITHROMYCIN4SLCO1B1
DIGOXIN4SLCO1B1
LOSARTAN4SLCO1B1
ERYTHROMYCIN ESTOLATE4SLCO1B1
TACROLIMUS ANHYDROUS4SLCO1B1
RIFAMPIN4SLCO1B1
ATORVASTATIN CALCIUM4SLCO1B1
SIROLIMUS4SLCO1B1
SULFASALAZINE4SLCO1B1
PACLITAXEL4SLCO1B1
RIFAMYCIN4SLCO1B1
GEMFIBROZIL4SLCO1B1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

SymbolAssaysType breakdown
SLCO1B1242Functional:106, ADMET:82, Binding:53, Toxicity:1

Cohort genes with high screening signal

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

SymbolChEMBL assays
SLCO1B1242

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

SymbolCPIC guidelines
SLCO1B11

Chemical tractability of cohort targets

30 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)
CANDESARTAN CILEXETIL4SLCO1B1
TELMISARTAN4SLCO1B1
SIMVASTATIN4SLCO1B1
TELITHROMYCIN4SLCO1B1
PRAVASTATIN4SLCO1B1
MOMETASONE FUROATE4SLCO1B1
ATAZANAVIR4SLCO1B1
HYDROXYZINE PAMOATE4SLCO1B1
ERYTHROMYCIN ETHYLSUCCINATE4SLCO1B1
OLMESARTAN MEDOXOMIL4SLCO1B1
DICLOXACILLIN SODIUM4SLCO1B1
BETA CAROTENE4SLCO1B1
NONOXYNOL 94SLCO1B1
ATORVASTATIN4SLCO1B1
VINBLASTINE4SLCO1B1
CYCLOSPORINE4SLCO1B1
RITONAVIR4SLCO1B1
CARBENOXOLONE SODIUM4SLCO1B1
CLARITHROMYCIN4SLCO1B1
DIGOXIN4SLCO1B1
LOSARTAN4SLCO1B1
ERYTHROMYCIN ESTOLATE4SLCO1B1
TACROLIMUS ANHYDROUS4SLCO1B1
RIFAMPIN4SLCO1B1
ATORVASTATIN CALCIUM4SLCO1B1
SIROLIMUS4SLCO1B1
SULFASALAZINE4SLCO1B1
PACLITAXEL4SLCO1B1
RIFAMYCIN4SLCO1B1
GEMFIBROZIL4SLCO1B1

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1SLCO1B1
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug1ILRUN
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1SYT9

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
SYT90—
ILRUN0—

Clinical trials & evidence

Clinical trials

Clinical trials: 16.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified8
PHASE35
PHASE41
PHASE2/PHASE31
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT01557140PHASE4COMPLETEDA Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT00323973PHASE3COMPLETEDChagas Cardiomyopathy Bisoprolol Intervention Study: Charity
NCT00349271PHASE3TERMINATEDCell Therapy in Chagas Cardiomyopathy
NCT02516293PHASE2/PHASE3COMPLETEDCardiac Rehabilitation in Chagas Heart Failure
NCT02517632PHASE3COMPLETEDPhysical Exercise Program in Chronic Chagas Heart Disease
NCT03193749PHASE3UNKNOWNA Trial Testing Amiodarone in Chagas Cardiomiopathy
NCT04853758PHASE3UNKNOWNAngiotensin Receptor-Neprilysin Inhibition in Chagas Cardiomyopathy With Reduced Ejection Fraction: ANSWER-HF.
NCT01863576EARLY_PHASE1COMPLETEDEffects of Omega-3 Supplementation on the Cytokine and Lipid Profiles in Patients With Chronic Chagas Cardiomyopathy
NCT05519046Not specifiedRECRUITINGCardiac Contractility Modulation in Chagas Heart Disease
NCT01340963Not specifiedCOMPLETEDThe Signal-averaged ElectrocArdiogram in Long Term Follow-up of Chronic CHagas Disease - RIO de Janeiro Cohort
NCT01722942Not specifiedUNKNOWNAmiodarone Against ICD Therapy in Chagas Cardiomyopathy for Primary Prevention of Death
NCT02099903Not specifiedUNKNOWNRenal Denervation in Patients With Heart Failure Secondary to Chagas Disease
NCT03524768Not specifiedCOMPLETEDMicrovascular Endothelial Function in a Cohort of Patients With the Cardiac Form of Chronic Chagas Disease.
NCT04090489Not specifiedCOMPLETEDCongenital Chagas Disease: Long Term Follow up of Treated Children. Preliminary Report or Cardiological Evaluation in Chagas Disease Treated Children
NCT04239144Not specifiedCOMPLETEDSympathetic Denervation by Video-assisted Thoracoscopy in Control of Cardiac Arrhythmias in Patients With Chagas Disease
NCT06806722Not specifiedCOMPLETEDCardiac Mechanics by Speckle Tracking as a Prognostic Predictor in Patients With Chagas Cardiomyopathy

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
BISOPROLOL43
ENALAPRIL43
AMIODARONE HYDROCHLORIDE42
FILGRASTIM41
SACUBITRIL41
OMEGA-3 FATTY ACIDS31

About this page

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

Generated
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Sources 70

This page pulls from 70 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot