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Atlas / Disease / Aortic valve calcification

Aortic valve calcification

disease
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Also known as aortic valve calcification (disease)

Summary

Aortic valve calcification (MONDO:0005463) is a disease with 15 cohort genes (70 GWAS associations across 8 studies) and 23 clinical trials. Top therapeutic interventions include colchicine, menatetrenone, and menaquinone 6.

At a glance

  • Cohort genes: 15
  • GWAS associations: 70
  • Clinical trials: 23

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameaortic valve calcification
Mondo IDMONDO:0005463
EFOEFO:0005239
SNOMED CT250978003
UMLSC0428791
MedGen140899
Is cancer (heuristic)no

Also known as: aortic valve calcification · aortic valve calcification (disease)

Data availability: 70 GWAS associations (8 studies) · 1 HPO phenotype.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › heart valve disorder › aortic valve disorder › aortic valve calcification

Related subtypes (4): aortic valve insufficiency, aortic valve prolapse, familial bicuspid aortic valve, aortic valve stenosis

Genetics & variants

GWAS landscape

70 GWAS associations across 8 studies. Top hits map to 34 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs104558723e-61LPAG
rs67026194e-40LINC01708G
rs111662762e-24LINC01708T1.15
rs75431306e-24LINC01708A1.14
rs728544622e-22TEX41A
rs18007971e-19STEAP1B, IL6, IL6-AS1A
rs75430391e-16LINC01708T1.24
rs10168191e-14PRRX1G
rs6821123e-14IPO9-AS1, NAV1A
rs14743477e-14IL6C1.1
rs107706127e-13TCP1P3 - LINC02468A
rs133111555e-12MTCYBP42 - TOMM7A1.1
rs17060033e-11RPL23AP93 - TMEM44-AS1G
rs22463634e-11TEX41A1.11
rs1118259501e-10ARHGEF26-AS1T
rs20775223e-10LINC01364 - RNA5SP52C
rs1745513e-10FADS2, FADS1T
rs621390614e-10ACTR2 - SPRED2C
rs122701468e-10MYEOV - LINC02956G
rs113308581e-09MECOMA
rs1872294352e-09PIDD1, RPLP2C
rs177669602e-09HMGA2 - MIR6074G
rs1504298852e-09TMEM170ACT
rs46466424e-09ALDH1A2A
rs31039336e-09MUC4A
rs115708917e-09LPLC
rs20698321e-08IL6A1.16
rs15223871e-08PPIAP16 - FLNBA1.08
rs178108521e-08SLC2A6 - MYMKG
rs1475583772e-08PDGFRAG

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90310293Theriault S202414,819941,863Integrative genomic analyses identify candidate causal genes for calcific aortic valve stenosis involving tissue-specific regulation.
GCST90271563Small AM202312,395287,787Multiancestry Genome-Wide Association Study of Aortic Stenosis Identifies Multiple Novel Loci in the Million Veteran Program.
GCST90271566Small AM202312,395287,787Multiancestry Genome-Wide Association Study of Aortic Stenosis Identifies Multiple Novel Loci in the Million Veteran Program.
GCST009870Theriault S20195,115354,072Genetic Association Analyses Highlight IL6, ALPL, and NAV1 As 3 New Susceptibility Genes Underlying Calcific Aortic Valve Stenosis.
GCST90271564Small AM20231,44579,299Multiancestry Genome-Wide Association Study of Aortic Stenosis Identifies Multiple Novel Loci in the Million Veteran Program.
GCST005785Theriault S20181,0091,017A transcriptome-wide association study identifies PALMD as a susceptibility gene for calcific aortic valve stenosis.
GCST90271565Small AM202361131,458Multiancestry Genome-Wide Association Study of Aortic Stenosis Identifies Multiple Novel Loci in the Million Veteran Program.
GCST001865Thanassoulis G201300Genetic associations with valvular calcification and aortic stenosis.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding2
Tier 2: splice/UTR2
Tier 3: regulatory2
Tier 4: intronic/intergenic44

MAF distribution

BucketVariants
common (>=0.05)46
low_freq (0.01-0.05)2
rare (<0.01)0
unknown2

Functional consequences

ConsequenceCount
intron_variant37
non_coding_transcript_exon_variant4
intergenic_variant2
regulatory_region_variant2
missense_variant2
3_prime_UTR_variant1
splice_polypyrimidine_tract_variant1
synonymous_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs104558726160589086A>G0.05intron_variantLPA3e-61Tier 4: intronic/intergenic
rs6702619199580690T>G0.05intron_variantLINC017084e-40Tier 4: intronic/intergenic
rs11166276199579683C>G,T0.49intron_variantLINC017082e-24Tier 4: intronic/intergenic
rs7543130199584229C>A0.05intron_variantLINC017086e-24Tier 4: intronic/intergenic
rs728544622144962572A>G0.05intron_variantTEX412e-22Tier 4: intronic/intergenic
rs1800797722726602A>C,G,T0.05non_coding_transcript_exon_variantSTEAP1B, IL6, IL6-AS11e-19Tier 4: intronic/intergenic
rs7543039199584092C>T0.486intron_variantLINC017081e-16Tier 4: intronic/intergenic
rs10168191170676633C>G0.05intron_variantPRRX11e-14Tier 4: intronic/intergenic
rs6821121201777640G>A,C,T0.05intron_variantIPO9-AS1, NAV13e-14Tier 4: intronic/intergenic
rs1474347722728505C>A,G0.05intron_variantIL67e-14Tier 4: intronic/intergenic
rs107706121220077705A>G,T0.05intron_variantTCP1P3 - LINC024687e-13Tier 4: intronic/intergenic
rs13311155722750170A>C,G,T0.41intergenic_variantMTCYBP42 - TOMM75e-12Tier 4: intronic/intergenic
rs17060033194579238G>A,C,T0.05intron_variantRPL23AP93 - TMEM44-AS13e-11Tier 4: intronic/intergenic
rs22463632145025715G>A,C0.25intron_variantTEX414e-11Tier 4: intronic/intergenic
rs1118259503154030503T>TTCAintron_variantARHGEF26-AS11e-10Tier 4: intronic/intergenic
rs2077522187452063C>T0.05intron_variantLINC01364 - RNA5SP523e-10Tier 4: intronic/intergenic
rs1745511161806212T>A,C0.05intron_variantFADS2, FADS13e-10Tier 4: intronic/intergenic
rs62139061265271671T>C0.05non_coding_transcript_exon_variantACTR2 - SPRED24e-10Tier 4: intronic/intergenic
rs122701461169348673A>G,T0.05intron_variantMYEOV - LINC029568e-10Tier 4: intronic/intergenic
rs113308583169484791AT>A0.05intron_variantMECOM1e-09Tier 4: intronic/intergenic
rs18722943511805953G>C,T0.05intron_variantPIDD1, RPLP22e-09Tier 4: intronic/intergenic
rs177669601266013637G>T0.05intergenic_variantHMGA2 - MIR60742e-09Tier 4: intronic/intergenic
rs1504298851675464355C>CT,CTT0.05intron_variantTMEM170A2e-09Tier 4: intronic/intergenic
rs46466421557954718A>G0.053_prime_UTR_variantALDH1A24e-09Tier 2: splice/UTR
rs31039333195758569A>C,G,T0.05intron_variantMUC46e-09Tier 4: intronic/intergenic
rs11570891819965299C>G,T0.05splice_polypyrimidine_tract_variantLPL7e-09Tier 2: splice/UTR
rs2069832722727814A>C,G,T0.428intron_variantIL61e-08Tier 4: intronic/intergenic
rs1522387357960369A>C,G0.05regulatory_region_variantPPIAP16 - FLNB1e-08Tier 3: regulatory
rs178108529133499953G>A,T0.05intron_variantSLC2A6 - MYMK1e-08Tier 4: intronic/intergenic
rs147558377454247456C>G0.05intron_variantPDGFRA2e-08Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 11 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
ARHGAP24Orphanet:656Hereditary steroid-resistant nephrotic syndrome
MECOMOrphanet:402020Acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2)
MECOMOrphanet:71289Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome
ALPLOrphanet:247623Perinatal lethal hypophosphatasia
ALPLOrphanet:247638Prenatal benign hypophosphatasia
ALPLOrphanet:247651Infantile hypophosphatasia
ALPLOrphanet:247667Childhood-onset hypophosphatasia
ALPLOrphanet:247676Adult hypophosphatasia
ALPLOrphanet:247685Odontohypophosphatasia
IL6Orphanet:85414Systemic-onset juvenile idiopathic arthritis
PRRX1Orphanet:990Agnathia-holoprosencephaly-situs inversus syndrome

Cohort genes → proteins

15 cohort genes, 14 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only15

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SNTG2HGNC:13741ENSG00000172554Q9NY99Gamma-2-syntrophingwas
PALMDHGNC:15846ENSG00000099260Q9NP74Palmdelphingwas
NAV1HGNC:15989ENSG00000134369Q8NEY1Neuron navigator 1gwas
ACTR2HGNC:169ENSG00000138071P61160Actin-related protein 2gwas
ARHGAP24HGNC:25361ENSG00000138639Q8N264Rho GTPase-activating protein 24gwas
DENND4CHGNC:26079ENSG00000137145Q5VZ89DENN domain-containing protein 4Cgwas
MIMS1HGNC:28346ENSG00000177150Q96ND0Protein FAM210Agwas
FBRSL1HGNC:29308ENSG00000112787Q9HCM7Fibrosin-1-like proteingwas
MECOMHGNC:3498ENSG00000085276Q03112Histone-lysine N-methyltransferase MECOMgwas
ALPLHGNC:438ENSG00000162551P05186Alkaline phosphatase, tissue-nonspecific isozymegwas
TEX41HGNC:48667ENSG00000226674testis expressed 41gwas
IL6HGNC:6018ENSG00000136244P05231Interleukin-6gwas
LPAHGNC:6667ENSG00000198670P08519Apolipoprotein(a)gwas
ME3HGNC:6985ENSG00000151376Q16798NADP-dependent malic enzyme, mitochondrialgwas
PRRX1HGNC:9142ENSG00000116132P54821Paired mesoderm homeobox protein 1gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SNTG2Gamma-2-syntrophinAdapter protein that binds to and probably organizes the subcellular localization of a variety of proteins.
NAV1Neuron navigator 1May be involved in neuronal migration.
ACTR2Actin-related protein 2ATP-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF).
ARHGAP24Rho GTPase-activating protein 24Rho GTPase-activating protein involved in cell polarity, cell morphology and cytoskeletal organization.
DENND4CDENN domain-containing protein 4CGuanine nucleotide exchange factor (GEF) activating RAB10.
MIMS1Protein FAM210AMay play a role in the structure and strength of both muscle and bone.
MECOMHistone-lysine N-methyltransferase MECOMFunctions as a transcriptional regulator binding to DNA sequences in the promoter region of target genes and regulating positively or negatively their expression.
ALPLAlkaline phosphatase, tissue-nonspecific isozymeAlkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis.
IL6Interleukin-6Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism.
LPAApolipoprotein(a)Apo(a) is the main constituent of lipoprotein(a) (Lp(a)).
ME3NADP-dependent malic enzyme, mitochondrialCatalyzes the oxidative decarboxylation of (S)-malate to pyruvate using NADP(+) as a cofactor.
PRRX1Paired mesoderm homeobox protein 1Master transcription factor of stromal fibroblasts for myofibroblastic lineage progression.

Protein-family classification

Druggable: 2 · Difficult: 4 · Unknown: 9 · Druggable fraction: 0.13

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
Phosphatase15.6×0.535
Scaffold/PPI22.3×0.535
Protease12.4×0.558
Transcription factor21.1×0.558
Other/Unknown91.1×0.558

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SNTG2Scaffold/PPInoPDZ, Syntrophin, PDZ_sf
PALMDOther/UnknownnoParalemmin
NAV1Other/UnknownnoAAA+_ATPase, P-loop_NTPase, Nav/unc-53
ACTR2Other/UnknownnoActin, Actin/actin-like_CS, ATPase_NBD
ARHGAP24Scaffold/PPInoRhoGAP_dom, PH_domain, Rho_GTPase_activation_prot
DENND4COther/UnknownnocDENN_dom, dDENN_dom, uDENN_dom
MIMS1Other/UnknownnoFAM210A/B-like_dom, FAM210A/B-like
FBRSL1Other/UnknownnoAUTS2
MECOMTranscription factornoSET_dom, Znf_C2H2_type, Znf_C2H2_sf
ALPLPhosphataseyes3.1.3.1Alkaline_phosphatase, Alkaline_phosphatase_core_sf, Alkaline_phosphatase_AS
TEX41Other/Unknownno
IL6Other/UnknownnoIL-6-like, 4_helix_cytokine-like_core, IL6/GCSF/MGF_CS
LPAProteaseyesKringle, Trypsin_dom, Peptidase_S1A
ME3Other/UnknownnoMalic_OxRdtase, Malic_N_dom, Malic_NAD-bd
PRRX1Transcription factornoHD, OAR_dom, Homeodomain-like_sf

Expression context

Cohort genes with no expression data: 0.

15 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)15
unknown0

Top tissues across cohort

TissueCohort genes
calcaneal tendon3
male germ line stem cell (sensu Vertebrata) in testis2
sural nerve2
apex of heart2
heart right ventricle2
left ventricle myocardium2
renal medulla2
right testis1
synovial joint1
endothelial cell1
lateral globus pallidus1
leukocyte1
monocyte1
mononuclear cell1
metanephros cortex1
pons1
jejunal mucosa1
skin of hip1
amniotic fluid1
cortical plate1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SNTG2166broadmarkersural nerve, male germ line stem cell (sensu Vertebrata) in testis, right testis
PALMD268broadmarkersynovial joint, heart right ventricle, apex of heart
NAV1252ubiquitousmarkerendothelial cell, lateral globus pallidus, left ventricle myocardium
ACTR2303ubiquitousmarkermonocyte, mononuclear cell, leukocyte
ARHGAP24263ubiquitousmarkerrenal medulla, pons, metanephros cortex
DENND4C282ubiquitousmarkerjejunal mucosa, skin of hip, calcaneal tendon
MIMS1250ubiquitousmarkerleft ventricle myocardium, amniotic fluid, heart right ventricle
FBRSL1248ubiquitousmarkerpancreatic ductal cell, oviduct epithelium, cortical plate
MECOM276ubiquitousmarkercardia of stomach, renal medulla, pylorus
ALPL200broadmarkerright adrenal gland, right adrenal gland cortex, left adrenal gland cortex
TEX41181broadmarkercalcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis, sural nerve
IL6200ubiquitousmarkercartilage tissue, vena cava, gall bladder
LPA100tissue_specificmarkerliver, right lobe of liver, adrenal tissue
ME3259ubiquitousmarkerapex of heart, left ovary, adenohypophysis
PRRX1266ubiquitousmarkercalcaneal tendon, tendon, urethra

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
IL69,239
ACTR24,733
MECOM2,442
ALPL2,146
PRRX12,036
ME31,562
NAV11,465
ARHGAP241,406
SNTG21,253
LPA1,200

Structural data

PDB: 8 · AlphaFold-only: 6 · No structure: 1

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
IL6P0523117
LPAP0851916
ACTR2P611605
ALPLP051865
ME3Q167985
SNTG2Q9NY991
DENND4CQ5VZ891
MECOMQ031121

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
ARHGAP24Q8N26466.68
PRRX1P5482166.38
PALMDQ9NP7465.92
MIMS1Q96ND064.73
NAV1Q8NEY150.18
FBRSL1Q9HCM746.19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 61. Enrichment computed across 15 evidence-associated genes (9 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 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
LDL remodeling1211.5×0.112LPA
MAPK1 (ERK2) activation1126.9×0.112IL6
CD163 mediating an anti-inflammatory response1126.9×0.112IL6
MAPK3 (ERK1) activation1115.3×0.112IL6
Interleukin-6 signaling1105.7×0.112IL6
Kidney development190.6×0.112MECOM
Formation of the nephric duct170.5×0.115MECOM
Plasma lipoprotein remodeling152.9×0.115LPA
Pyruvate metabolism145.3×0.115ME3
Parasite infection138.5×0.115ACTR2
Leishmania phagocytosis138.5×0.115ACTR2
RHO GTPases Activate WASPs and WAVEs135.2×0.115ACTR2
Formation of the dystrophin-glycoprotein complex (DGC)134.3×0.115SNTG2
Fcgamma receptor (FCGR) dependent phagocytosis130.9×0.115ACTR2
EPHB-mediated forward signaling129.5×0.115ACTR2
Transcriptional Regulation by VENTX129.5×0.115IL6
ADORA2B mediated anti-inflammatory cytokines production128.2×0.115IL6
Interleukin-10 signaling125.9×0.115IL6
Plasma lipoprotein assembly, remodeling, and clearance125.4×0.115LPA
PTEN Regulation125.4×0.115MECOM
FCGR3A-mediated phagocytosis120.8×0.115ACTR2
Regulation of actin dynamics for phagocytic cup formation120.5×0.115ACTR2
Regulation of PTEN gene transcription119.8×0.115MECOM
Post-translational modification: synthesis of GPI-anchored proteins118.7×0.115ALPL
EPH-Ephrin signaling118.4×0.115ACTR2
Leishmania infection118.1×0.115ACTR2
Parasitic Infection Pathways118.1×0.115ACTR2
Activation of STAT3 by cadherin engagement118.1×0.115IL6
PKMTs methylate histone lysines117.9×0.115MECOM
Non-integrin membrane-ECM interactions117.1×0.116SNTG2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 12 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
pyridoxal 5’-phosphate metabolic process11404.3×0.024ALPL
regulation of neuron projection regeneration11404.3×0.024PRRX1
meiotic chromosome movement towards spindle pole1702.2×0.024ACTR2
cytosolic transport1702.2×0.024ACTR2
meiotic cytokinesis1702.2×0.024ACTR2
response to vitamin B61702.2×0.024ALPL
regulation of astrocyte activation1702.2×0.024IL6
glucagon secretion1702.2×0.024IL6
futile creatine cycle1702.2×0.024ALPL
neutrophil apoptotic process1468.1×0.024IL6
hepatic immune response1468.1×0.024IL6
positive regulation of interleukin-21 production1468.1×0.024IL6
regulation of vascular endothelial growth factor production1351.1×0.024IL6
negative regulation of Rac protein signal transduction1351.1×0.024ARHGAP24
response to macrophage colony-stimulating factor1351.1×0.024ALPL
regulation of glucagon secretion1351.1×0.024IL6
inhibition of non-skeletal tissue mineralization1351.1×0.024ALPL
regulation of microglial cell activation1351.1×0.024IL6
negative regulation of primary miRNA processing1351.1×0.024IL6
response to glucocorticoid254.0×0.024ALPL, IL6
developmental process involved in reproduction1280.9×0.026ALPL
spindle localization1280.9×0.026ACTR2
positive regulation of apoptotic DNA fragmentation1234.1×0.026IL6
asymmetric cell division1200.6×0.026ACTR2
vascular endothelial growth factor production1200.6×0.026IL6
regulation of Rab protein signal transduction1200.6×0.026DENND4C
response to peptidoglycan1200.6×0.026IL6
cementum mineralization1200.6×0.026ALPL
negative regulation of ruffle assembly1200.6×0.026ARHGAP24
positive regulation of type B pancreatic cell apoptotic process1200.6×0.026IL6

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 12

Druggability breadth: 6 of 15 evidence-associated genes (40%) 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
ALPLSULCONAZOLE NITRATE
IL6PREDNISOLONE

Top cohort targets by molecule count

SymbolMoleculesMax phase
ALPL74
IL634
ACTR212
SNTG200
PALMD00
NAV100
ARHGAP2400
DENND4C00
MIMS100
FBRSL100

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
SULCONAZOLE NITRATE4ALPL
THEOPHYLLINE4ALPL
LEVAMISOLE4ALPL
MICONAZOLE NITRATE4ALPL
LEVAMISOLE HYDROCHLORIDE4ALPL
PREDNISOLONE4IL6
TALMAPIMOD2ACTR2
ISOQUERCETIN2ALPL
(-)-EPICATECHIN2ALPL
FOSDAGROCORAT2IL6
BI 6530481IL6

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

SymbolAssaysType breakdown
ALPL58Binding:50, Functional:4, ADMET:3, Toxicity:1
ACTR223Binding:23
IL616Binding:16
ME313Binding:13
PRRX111Binding:11
MECOM1Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
ALPL3.1.3.1alkaline phosphatase

Pharmacogenomics

Cohort genes with a PharmGKB record: 14; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

11 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)
SULCONAZOLE NITRATE4ALPL
THEOPHYLLINE4ALPL
LEVAMISOLE4ALPL
MICONAZOLE NITRATE4ALPL
LEVAMISOLE HYDROCHLORIDE4ALPL
PREDNISOLONE4IL6
TALMAPIMOD2ACTR2
ISOQUERCETIN2ALPL
(-)-EPICATECHIN2ALPL
FOSDAGROCORAT2IL6
BI 6530481IL6

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)2ALPL, IL6
BPhased (≥1) drug, not yet approved1ACTR2
CDruggable family + PDB, no drug1LPA
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug11SNTG2, PALMD, NAV1, ARHGAP24, DENND4C, MIMS1, FBRSL1, MECOM, TEX41, ME3 (+1 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
SNTG20—
PALMD0—
NAV10—
ARHGAP240—
DENND4C0—
MIMS10—
FBRSL10—
MECOM1—
TEX410—
LPA0—
ME313—
PRRX111—

Clinical trials & evidence

Clinical trials

Clinical trials: 23.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified21
PHASE32

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05162742PHASE3ACTIVE_NOT_RECRUITINGColchicine and Inflammation in Aortic Stenosis
NCT00785109PHASE3COMPLETEDVitamin K Supplement for Inhibition of the Progress in Aortic Valve Calcification
NCT04149600Not specifiedACTIVE_NOT_RECRUITINGIdentification of Genetic Causes of Calcific Aortic Valve Disease
NCT04655248Not specifiedACTIVE_NOT_RECRUITINGACURATE neo2™ Post Market Clinical Follow up Study
NCT05712161Not specifiedACTIVE_NOT_RECRUITINGUse of DurAVR™ THV System in Subjects With Severe Aortic Stenosis: Early Feasibility Study
NCT05851209Not specifiedNOT_YET_RECRUITINGBiomarkers and Mechanisms of Disease Progression and Outcome of Aortic Stenosis in Humans
NCT06510855Not specifiedACTIVE_NOT_RECRUITINGDurAVR™ THV EU-EFS
NCT06688448Not specifiedRECRUITINGValvular Assessment of New Generation Aortic Replacement Devices
NCT07520591Not specifiedNOT_YET_RECRUITINGValvosoft Outcomes Registry for Real-World Evidence
NCT01383720Not specifiedCOMPLETEDREpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus™ Valve SystEm
NCT01683474Not specifiedUNKNOWNSafety and Performance of TAVI of Venus MedTech Aortic Valve Prosthesis
NCT01755806Not specifiedCOMPLETEDComparison of Aortic Root Dimension Changes During Cardiac Cycle Between the Patients With and Without Aortic Valve Calcification Using ECG-gated 64-slice and Dual-source 256-slice Computed Tomography Scanners: Results of a Multicenter Study
NCT02221921Not specifiedUNKNOWNSafety and Efficacy Study of MicroPort’s Transcatheter Aortic Valve and Delivery System for TAVI
NCT02516800Not specifiedUNKNOWNPrevalence and Significance of Mutations in Genes Encoding NaPi-co-transporters in the Development of CAVD
NCT04056832Not specifiedUNKNOWNLeft Ventricular Reverse Remodeling In Aortic Valve Replacement With Single Strip Pericardium Versus Mechanical Valve
NCT04429035Not specifiedUNKNOWNSLOW-Slower Progress of caLcificatiOn With Vitamin K2
NCT04557345Not specifiedCOMPLETEDEvaluation of the Inflammatory Response in Post-operated Aortic Valve Replacement Patients.
NCT05182307Not specifiedUNKNOWNDurAVR™ THV System: First-In-Human Study
NCT05235568Not specifiedCOMPLETEDVALVOSOFT® Pivotal Study
NCT05975567Not specifiedUNKNOWNDeploying Novel Imaging Modalities Towards a Three-dimensional (3D) CARDIOvascular PATHology
NCT06136689Not specifiedUNKNOWNRole of Aortic Valve Composition in Pathophysiology and Diagnosis of Aortic Stenosis
NCT06192706Not specifiedUNKNOWNClinical Investigation for the Foldax Tria Aortic Heart Valve- India
NCT06959862Not specifiedWITHDRAWNACURATE Enhance Post Market Study

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
COLCHICINE41
MENATETRENONE31
MENAQUINONE 621
MENAQUINONE-201

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
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 68

This page pulls from 68 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot