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Hypotensive disorder

disease
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Also known as hypotensionhypotension (disease)

Summary

Hypotensive disorder (MONDO:0005468) is a disease (an umbrella term covering 5 Mondo subtypes) with 7 cohort genes (18 GWAS associations across 33 studies) and 371 clinical trials. Top therapeutic interventions include norepinephrine, ephedrine, and phenylephrine.

At a glance

  • Umbrella term: 5 Mondo subtypes
  • Cohort genes: 7
  • GWAS associations: 18
  • ClinVar variants: 29
  • Clinical trials: 371

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namehypotensive disorder
Mondo IDMONDO:0005468
EFOEFO:0005251
MeSHD007022
ICD-10-CMI95
ICD-111663360295
SNOMED CT45007003
UMLSC0020649
MedGen5715
Is cancer (heuristic)no

Also known as: hypotension · hypotension (disease)

Data availability: 29 ClinVar variants · 18 GWAS associations (33 studies) · 1 HPO phenotype.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › arterial disorder › hypotensive disorder

Related subtypes (29): vertebral artery insufficiency, splenic artery aneurysm, basilar artery insufficiency, arteriosclerosis disorder, subclavian artery aneurysm, pulmonary artery choriocarcinoma, pulmonary artery leiomyosarcoma, coronary artery disorder, hypertensive disorder, carotid artery disorder, pulmonary embolism, peripheral arterial disease, large artery stroke, aortic disorder, cervical artery dissection, anterior spinal artery syndrome, fibromuscular dysplasia, retinal arterial tortuosity, Sneddon syndrome, celiac trunk compression syndrome, pediatric arterial ischemic stroke, absence of the pulmonary artery, arterial occlusion, aberrant subclavian artery, anterior spinal artery stroke, arteritis, pulmonary artery disease, fibromuscular dysplasia, multifocal, carotid web

Subtypes (5): supine hypotensive syndrome, acute hypotension, orthostatic hypotension, postprandial hypotension, neurally mediated hypotension

Genetics & variants

GWAS landscape

18 GWAS associations across 33 studies. Top hits map to 10 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs5564631742e-14FOXO1G2.7
rs5290288268e-14SDC2G2.35
rs5563221981e-12SLC1A5 - HNRNPMP2T3.74
rs1919645472e-12NKAIN2G2.62
rs5308666002e-11LINC02196C2.94
rs5386808952e-11RYR2C2.75
rs3757640763e-11RYR3C3.2
rs5556978823e-11NLRP1 - WSCD1A2.48
rs1920726963e-11MGAT5BA2.73
rs5429040134e-11RNASE11 - OR6S1A3.41
rs1380292916e-09HNRNPA1P57 - LDHAP3?
chr4:468667781e-08T2.47
rs1413381964e-08LINC02473 - HNRNPA1P65?
chr1:1606047124e-08A2.28
chr4:447168824e-08T2.46
rs1171290971e-06LINC02441 - LINC02369T4.03
rs133884596e-06LRRTM4-AS1, LRRTM4T2.85
rs105214678e-06PCSK5G2.94

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90478054Verma A202438,699374,548Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90478062Verma A202422,869398,730Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473625UK Biobank Whole-Genome Sequencing Consortium202521,266437,174Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90667797UK Biobank Whole-Genome Sequencing Consortium202521,266437,174Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90478053Verma A20249,298102,629Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480816Verma A20249,298102,629Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90080083Backman JD20217,547378,733Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084069Backman JD20217,547378,733Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90436183Zhou W20185,827387,905Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90478061Verma A20245,728108,420Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR1
Tier 3: regulatory1
Tier 4: intronic/intergenic16

MAF distribution

BucketVariants
common (>=0.05)4
low_freq (0.01-0.05)0
rare (<0.01)10
unknown4

Functional consequences

ConsequenceCount
intron_variant11
unknown3
intergenic_variant2
regulatory_region_variant1
splice_polypyrimidine_tract_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs5564631741340630384G>A,C0intron_variantFOXO12e-14Tier 4: intronic/intergenic
rs529028826896501995G>A0intron_variantSDC28e-14Tier 4: intronic/intergenic
rs5563221981946795091T>A,C0intergenic_variantSLC1A5 - HNRNPMP21e-12Tier 4: intronic/intergenic
rs1919645476124559100G>A0.001intron_variantNKAIN22e-12Tier 4: intronic/intergenic
rs53086660056848067C>A,T0intron_variantLINC021962e-11Tier 4: intronic/intergenic
rs5386808951237803501C>A,G,T0.001intron_variantRYR22e-11Tier 4: intronic/intergenic
rs3757640761533644292C>G,T0.001intron_variantRYR33e-11Tier 4: intronic/intergenic
rs555697882176056319A>G0.001intron_variantNLRP1 - WSCD13e-11Tier 4: intronic/intergenic
rs1920726961776944613A>G,T0intron_variantMGAT5B3e-11Tier 4: intronic/intergenic
rs5429040131420631249A>C,G,T0.001regulatory_region_variantRNASE11 - OR6S14e-11Tier 3: regulatory
rs138029291241495938C>G0.05intron_variantHNRNPA1P57 - LDHAP36e-09Tier 4: intronic/intergenic
chr4:468667781e-08Tier 4: intronic/intergenic
rs141338196424672638G>Aintergenic_variantLINC02473 - HNRNPA1P654e-08Tier 4: intronic/intergenic
chr1:1606047124e-08Tier 4: intronic/intergenic
chr4:447168824e-08Tier 4: intronic/intergenic
rs11712909712128054737C>A,G,T0.06splice_polypyrimidine_tract_variantLINC02441 - LINC023691e-06Tier 2: splice/UTR
rs13388459276988371C>A,T0.14intron_variantLRRTM4-AS1, LRRTM46e-06Tier 4: intronic/intergenic
rs10521467976036575A>G0.12intron_variantPCSK58e-06Tier 4: intronic/intergenic

ClinVar germline variants

29 retrieved; paginated sample, class counts are floors:

9 not provided, 9 benign, 5 benign/likely benign, 4 likely benign, 2 uncertain significance

ClinVarVariant (HGVS)GeneClassificationReview
120234NM_017637.6(BNC2):c.2051C>T (p.Pro684Leu)BNC2Uncertain significancecriteria provided, single submitter
523536NM_030662.4(MAP2K2):c.514A>G (p.Lys172Glu)MAP2K2Uncertain significancecriteria provided, multiple submitters, no conflicts
132789NM_001818.5(AKR1C4):c.447+9T>GAKR1C4Benigncriteria provided, single submitter
120226NM_017637.6(BNC2):c.1002A>G (p.Pro334=)BNC2Likely benigncriteria provided, single submitter
120228NM_017637.6(BNC2):c.1240C>G (p.Leu414Val)BNC2Benigncriteria provided, multiple submitters, no conflicts
120229NM_017637.6(BNC2):c.1545A>G (p.Ser515=)BNC2Benigncriteria provided, multiple submitters, no conflicts
120230NM_017637.6(BNC2):c.171G>T (p.Gln57His)BNC2Benigncriteria provided, single submitter
120232NM_017637.6(BNC2):c.1868C>A (p.Pro623His)BNC2Benign/Likely benigncriteria provided, multiple submitters, no conflicts
120233NM_017637.6(BNC2):c.1947C>T (p.Thr649=)BNC2Benign/Likely benigncriteria provided, multiple submitters, no conflicts
120236NM_017637.6(BNC2):c.2478A>G (p.Leu826=)BNC2Benigncriteria provided, multiple submitters, no conflicts
120237NM_017637.6(BNC2):c.2739C>T (p.Arg913=)BNC2Likely benigncriteria provided, single submitter
120238NM_017637.6(BNC2):c.2768C>T (p.Ala923Val)BNC2Benign/Likely benigncriteria provided, multiple submitters, no conflicts
120239NM_017637.6(BNC2):c.2789A>G (p.Asp930Gly)BNC2Likely benigncriteria provided, multiple submitters, no conflicts
120240NM_017637.6(BNC2):c.2920A>G (p.Ile974Val)BNC2Benigncriteria provided, multiple submitters, no conflicts
120241NM_017637.6(BNC2):c.501C>T (p.Val167=)BNC2Likely benigncriteria provided, single submitter
120242NM_017637.6(BNC2):c.519C>T (p.Ser173=)BNC2Benign/Likely benigncriteria provided, multiple submitters, no conflicts
120243NM_017637.6(BNC2):c.84A>T (p.Ala28=)BNC2Benigncriteria provided, multiple submitters, no conflicts
120244NM_017637.6(BNC2):c.916C>G (p.Pro306Ala)BNC2Benigncriteria provided, single submitter
120245NM_017637.6(BNC2):c.936C>T (p.Phe312=)BNC2Benigncriteria provided, multiple submitters, no conflicts
132786NM_001300.6(KLF6):c.603G>A (p.Arg201=)KLF6Benign/Likely benigncriteria provided, multiple submitters, no conflicts
132790NM_003739.6(AKR1C3):c.643G>A (p.Ala215Thr)AKR1C3not providedno classification provided
120227NM_017637.6(BNC2):c.1239T>C (p.Asp413=)BNC2not providedno classification provided
120231NM_017637.6(BNC2):c.1738G>A (p.Gly580Arg)BNC2not providedno classification provided
120235NM_017637.6(BNC2):c.2202C>T (p.Gly734=)BNC2not providedno classification provided
132783NM_001300.6(KLF6):c.*46A>TKLF6not providedno classification provided
132784NM_001300.6(KLF6):c.*62G>AKLF6not providedno classification provided
132785NM_001300.6(KLF6):c.496C>T (p.Pro166Ser)KLF6not providedno classification provided
132787NM_001300.6(KLF6):c.800+21C>TKLF6not providedno classification provided
132788NM_001300.6(KLF6):c.800+34G>AKLF6not providedno classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
BNC2Orphanet:93110Posterior urethral valve
AKR1C4Orphanet:44308746,XY difference of sex development due to testicular 17,20-desmolase deficiency
MAP2K2Orphanet:1340Cardiofaciocutaneous syndrome
MAP2K2Orphanet:638Neurofibromatosis-Noonan syndrome

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only2
multi_evidence5

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
LRRTM4HGNC:19411ENSG00000176204Q86VH4Leucine-rich repeat transmembrane neuronal protein 4gwas
KLF6HGNC:2235ENSG00000067082Q99612Krueppel-like factor 6clinvar
BNC2HGNC:30988ENSG00000173068Q6ZN30Zinc finger protein basonuclin-2clinvar
AKR1C3HGNC:386ENSG00000196139P42330Aldo-keto reductase family 1 member C3clinvar
AKR1C4HGNC:387ENSG00000198610P17516Aldo-keto reductase family 1 member C4clinvar
MAP2K2HGNC:6842ENSG00000126934P36507Dual specificity mitogen-activated protein kinase kinase 2clinvar
PCSK5HGNC:8747ENSG00000099139Q92824Proprotein convertase subtilisin/kexin type 5gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
LRRTM4Leucine-rich repeat transmembrane neuronal protein 4May play a role in the development and maintenance of the vertebrate nervous system.
KLF6Krueppel-like factor 6Transcriptional activator.
BNC2Zinc finger protein basonuclin-2Probable transcription factor specific for skin keratinocytes.
AKR1C3Aldo-keto reductase family 1 member C3Cytosolic aldo-keto reductase that catalyzes NADPH-dependent reduction of ketosteroids to hydroxysteroids.
AKR1C4Aldo-keto reductase family 1 member C4Cytosolic aldo-keto reductase that catalyzes NADPH-dependent reduction of ketosteroids to hydroxysteroids.
MAP2K2Dual specificity mitogen-activated protein kinase kinase 2Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases.
PCSK5Proprotein convertase subtilisin/kexin type 5Serine endoprotease that processes various proproteins by cleavage at paired basic amino acids, recognizing the RXXX[KR]R consensus motif.

Protein-family classification

Druggable: 4 · Difficult: 2 · Unknown: 1 · Druggable fraction: 0.57

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
Protease15.2×0.283
Kinase14.0×0.283
Enzyme (other)23.4×0.283
Transcription factor22.4×0.283
Other/Unknown10.3×0.997

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
LRRTM4Other/UnknownnoLeu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRR_dom_sf
KLF6Transcription factornoZnf_C2H2_type, Znf_C2H2_sf
BNC2Transcription factornoZnf_C2H2_type, Disconnected-like
AKR1C3Enzyme (other)yes1.1.1.188Aldo/ket_reductase_CS, AKR, NADP_OxRdtase_dom
AKR1C4Enzyme (other)yes1.1.1.357Aldo/ket_reductase_CS, AKR, NADP_OxRdtase_dom
MAP2K2Kinaseyes2.7.12.2Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
PCSK5Proteaseyes3.4.21.B26Peptidase_S8/S53_dom, EGF, P_dom

Expression context

Cohort genes with no expression data: 0.

7 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)7
unknown0

Top tissues across cohort

TissueCohort genes
sural nerve2
gall bladder2
cortical plate1
oocyte1
secondary oocyte1
lower lobe of lung1
nipple1
upper leg skin1
germinal epithelium of ovary1
parietal pleura1
jejunal mucosa1
pancreatic ductal cell1
liver1
right lobe of liver1
left testis1
mucosa of transverse colon1
right testis1
buccal mucosa cell1
saphenous vein1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
LRRTM4144broadmarkersecondary oocyte, oocyte, cortical plate
KLF6301ubiquitousmarkernipple, lower lobe of lung, upper leg skin
BNC2229ubiquitousmarkergerminal epithelium of ovary, sural nerve, parietal pleura
AKR1C3285ubiquitousmarkerjejunal mucosa, pancreatic ductal cell, gall bladder
AKR1C474tissue_specificmarkerright lobe of liver, liver, gall bladder
MAP2K2291ubiquitousmarkermucosa of transverse colon, right testis, left testis
PCSK5264ubiquitousmarkerbuccal mucosa cell, saphenous vein, sural nerve

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

SymbolInteractor count
MAP2K23,789
PCSK52,359
KLF62,158
AKR1C31,765
LRRTM41,671
AKR1C41,180
BNC21,104

Intra-cohort edges

ABSources
AKR1C3AKR1C4biogrid_interaction, intact

Structural data

PDB: 3 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
AKR1C3P4233067
MAP2K2P365073
AKR1C4P175161

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
PCSK5Q9282476.31
LRRTM4Q86VH474.45
KLF6Q9961259.24
BNC2Q6ZN3054.10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 60. Enrichment computed across 7 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Synthesis of bile acids and bile salts via 24-hydroxycholesterol2351.4×5e-04AKR1C3, AKR1C4
Synthesis of bile acids and bile salts via 27-hydroxycholesterol2304.5×5e-04AKR1C3, AKR1C4
Bile acid and bile salt metabolism2198.6×7e-04AKR1C3, AKR1C4
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol2182.7×7e-04AKR1C3, AKR1C4
Synthesis of bile acids and bile salts2163.1×7e-04AKR1C3, AKR1C4
Metabolism of fat-soluble vitamins2152.3×7e-04AKR1C3, AKR1C4
Visual phototransduction2103.8×0.001AKR1C3, AKR1C4
Retinoid metabolism and transport299.3×0.001AKR1C3, AKR1C4
Metabolism of steroids255.0×0.003AKR1C3, AKR1C4
Metabolism of vitamins and cofactors246.6×0.004AKR1C3, AKR1C4
Sensory Perception238.1×0.006AKR1C3, AKR1C4
NGF processing1571.0×0.008PCSK5
Signaling by MAP2K mutants1571.0×0.008MAP2K2
Negative feedback regulation of MAPK pathway1380.7×0.011MAP2K2
Prolonged ERK activation events1285.5×0.014MAP2K2
MAPK1 (ERK2) activation1228.4×0.016MAP2K2
Frs2-mediated activation1190.3×0.017MAP2K2
Uptake and function of anthrax toxins1190.3×0.017MAP2K2
Uptake and actions of bacterial toxins1163.1×0.019MAP2K2
Synthesis of Prostaglandins (PG) and Thromboxanes (TX)1152.3×0.020AKR1C3
RAF-independent MAPK1/3 activation1126.9×0.022MAP2K2
Signalling to ERKs1120.2×0.022MAP2K2
Assembly of active LPL and LIPC lipase complexes1120.2×0.022PCSK5
Arachidonate metabolism1114.2×0.022AKR1C3
Signal transduction by L11103.8×0.022MAP2K2
Metabolism of lipids212.6×0.022AKR1C3, AKR1C4
RA biosynthesis pathway195.2×0.023AKR1C3
Signaling by RAS mutants184.6×0.025MAP2K2
Signaling by Retinoic Acid181.6×0.025AKR1C3
RAF activation167.2×0.029MAP2K2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
cellular response to jasmonic acid stimulus21203.7×7e-05AKR1C3, AKR1C4
progesterone metabolic process2481.5×2e-04AKR1C3, AKR1C4
daunorubicin metabolic process2437.7×2e-04AKR1C3, AKR1C4
doxorubicin metabolic process2370.4×2e-04AKR1C3, AKR1C4
prostaglandin metabolic process2240.7×4e-04AKR1C3, AKR1C4
retinoid metabolic process2141.6×0.001AKR1C3, AKR1C4
steroid metabolic process296.3×0.002AKR1C3, AKR1C4
macromolecule metabolic process12407.4×0.003AKR1C3
cellular response to prostaglandin stimulus12407.4×0.003AKR1C3
cellular response to corticosteroid stimulus12407.4×0.003AKR1C3
negative regulation of retinoic acid biosynthetic process11203.7×0.006AKR1C3
farnesol catabolic process1802.5×0.007AKR1C3
negative regulation of low-density lipoprotein particle receptor catabolic process1802.5×0.007PCSK5
regulation of retinoic acid receptor signaling pathway1802.5×0.007AKR1C3
renin secretion into blood stream1601.9×0.007PCSK5
viral life cycle1601.9×0.007PCSK5
plasma lipoprotein particle remodeling1601.9×0.007PCSK5
peptide biosynthetic process1601.9×0.007PCSK5
regulation of Golgi inheritance1601.9×0.007MAP2K2
respiratory tube development1481.5×0.007PCSK5
peptidyl-serine autophosphorylation1481.5×0.007MAP2K2
epithelial cell proliferation involved in lung morphogenesis1481.5×0.007MAP2K2
cytokine precursor processing1481.5×0.007PCSK5
regulation of testosterone biosynthetic process1481.5×0.007AKR1C3
testosterone biosynthetic process1401.2×0.008AKR1C3
prostanoid biosynthetic process1343.9×0.008AKR1C3
regulation of axon regeneration1343.9×0.008MAP2K2
trachea formation1343.9×0.008MAP2K2
mesenchyme development1343.9×0.008BNC2
cellular response to prostaglandin D stimulus1343.9×0.008AKR1C3

Therapeutics

Drugs indicated for this disease

0 approved, 11 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
Drotrecogin Alfa (Activated)Phase 3 (in late-stage trials)
EphedrinePhase 3 (in late-stage trials)
HydrocortisonePhase 3 (in late-stage trials)
IcatibantPhase 3 (in late-stage trials)
LevocarnitinePhase 3 (in late-stage trials)
MidodrinePhase 3 (in late-stage trials)
NorepinephrinePhase 3 (in late-stage trials)
OndansetronPhase 3 (in late-stage trials)
PhenylephrinePhase 3 (in late-stage trials)
RopivacainePhase 3 (in late-stage trials)
Sodium ChloridePhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Bupivacaine, Droxidopa, Epinephrine, Fentanyl, Fospropofol, Ivabradine, Lanadelumab, Mannitol, Metaraminol, Midazolam, Nitroprusside, Propofol, Propranolol.

Drug target analysis

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

Druggability breadth: 4 of 7 evidence-associated genes (57%) 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
AKR1C3DICLOFENAC SODIUM
AKR1C4FLURBIPROFEN
MAP2K2VEMURAFENIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
MAP2K2524
AKR1C3224
AKR1C424
LRRTM400
KLF600
BNC200
PCSK500

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
DICLOFENAC SODIUM4AKR1C3
DIAZEPAM4AKR1C3
BIMATOPROST4AKR1C3
GLIMEPIRIDE4AKR1C3
NAPROXEN4AKR1C3
DEXIBUPROFEN4AKR1C3
BERBERINE4AKR1C3
GLICLAZIDE4AKR1C3
MECLOFENAMIC ACID4AKR1C3
IBUPROFEN4AKR1C3
FLURBIPROFEN4AKR1C3, AKR1C4
INDOMETHACIN4AKR1C3, AKR1C4
MEFENAMIC ACID4AKR1C3
MEDROXYPROGESTERONE ACETATE4AKR1C3
VEMURAFENIB4MAP2K2
SELUMETINIB4MAP2K2
TRAMETINIB4MAP2K2
COBIMETINIB4MAP2K2
BINIMETINIB4MAP2K2
DASATINIB4MAP2K2
FEDRATINIB4MAP2K2
AXITINIB4MAP2K2
RUXOLITINIB4MAP2K2
NERATINIB4MAP2K2
VANDETANIB4MAP2K2
BOSUTINIB4MAP2K2
GILTERITINIB4MAP2K2
NINTEDANIB4MAP2K2
SUNITINIB4MAP2K2
BUPARLISIB3AKR1C3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

SymbolAssaysType breakdown
MAP2K2615Binding:581, Functional:33, ADMET:1
AKR1C3204Binding:197, ADMET:7
AKR1C432Binding:29, ADMET:3
PCSK54Binding:4

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
AKR1C31.1.1.188, 1.1.1.21, 1.1.1.213, 1.1.1.239, 1.1.1.357, 1.1.1.51, 1.1.1.62, 1.1.1.64, 1.3.1.20prostaglandin-F synthase, aldose reductase, 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific), 3alpha(17beta)-hydroxysteroid dehydrogenase (NAD+), 3alpha-hydroxysteroid 3-dehydrogenase, 3(or 17)beta-hydroxysteroid dehydrogenase, 17beta-estradiol 17-dehydrogenase, testosterone 17beta-dehydrogenase (NADP+), trans-1,2-dihydrobenzene-1,2-diol dehydrogenase
AKR1C41.1.1.3573alpha-hydroxysteroid 3-dehydrogenase
MAP2K22.7.12.2mitogen-activated protein kinase kinase
PCSK53.4.21.B26

Cohort genes with high screening signal

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

SymbolChEMBL assays
AKR1C3204
MAP2K2615

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.

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

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)
DICLOFENAC SODIUM4AKR1C3
DIAZEPAM4AKR1C3
BIMATOPROST4AKR1C3
GLIMEPIRIDE4AKR1C3
NAPROXEN4AKR1C3
DEXIBUPROFEN4AKR1C3
BERBERINE4AKR1C3
GLICLAZIDE4AKR1C3
MECLOFENAMIC ACID4AKR1C3
IBUPROFEN4AKR1C3
FLURBIPROFEN4AKR1C3, AKR1C4
INDOMETHACIN4AKR1C3, AKR1C4
MEFENAMIC ACID4AKR1C3
MEDROXYPROGESTERONE ACETATE4AKR1C3
VEMURAFENIB4MAP2K2
SELUMETINIB4MAP2K2
TRAMETINIB4MAP2K2
COBIMETINIB4MAP2K2
BINIMETINIB4MAP2K2
DASATINIB4MAP2K2
FEDRATINIB4MAP2K2
AXITINIB4MAP2K2
RUXOLITINIB4MAP2K2
NERATINIB4MAP2K2
VANDETANIB4MAP2K2
BOSUTINIB4MAP2K2
GILTERITINIB4MAP2K2
NINTEDANIB4MAP2K2
SUNITINIB4MAP2K2
BUPARLISIB3AKR1C3

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)3AKR1C3, AKR1C4, MAP2K2
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug1PCSK5
EDifficult family or no structure, no drug3LRRTM4, KLF6, BNC2

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
LRRTM40—
KLF60—
BNC20—
PCSK54—

Clinical trials & evidence

Clinical trials

Clinical trials: 371.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified256
PHASE450
PHASE222
PHASE320
PHASE2/PHASE311
PHASE16
PHASE1/PHASE24
EARLY_PHASE12

Top trials by phase / activity

NCTPhaseStatusTitle
NCT02004834PHASE4ACTIVE_NOT_RECRUITINGLevobupivacaine and Lidocaine for Paravertebral Block Causes Greater Hemodynamic Oscillations Than Levobupivacaine
NCT02323399PHASE4RECRUITINGStudy to Determine the Pharmacokinetics and Pharmacodynamic Effects of Phenylephrine on BP Via IV
NCT04705896PHASE4RECRUITINGAlbumin To Enhance Recovery After Acute Kidney Injury
NCT05836610PHASE4RECRUITINGHydrocortisone Therapy Optimization During Hypothermia Treatment in Asphyxiated Neonates
NCT05839652PHASE4RECRUITINGTreatment of Orthostatic Hypotension in SCI
NCT06248593PHASE4RECRUITINGContinuous Infusion of Norepinephrine vs Phenylephrine During Spinal Anesthesia for Cesarean Section (INPEACE)
NCT06257316PHASE4NOT_YET_RECRUITINGAppropriate Dosage of Vasopressor in Neonates and Infants
NCT06832566PHASE4NOT_YET_RECRUITINGRamadan Fasting Outcomes in Patients With Secondary Adrenal Insufficiency Before and After the Treatment of Hypotension.
NCT00115726PHASE4COMPLETEDTrial Assessing the Effect of Preoperative Furosemide on Intraoperative Blood Pressure
NCT00173706PHASE4UNKNOWNEvaluation of the Effects of L-Carnitine Injection in Patients Undergoing Hemodialysis
NCT00694343PHASE4COMPLETEDEfficacy of Voluven® for the Prevention of Hypotension During Spinal Anesthesia for Cesarean Section
NCT00777166PHASE4COMPLETEDCardiac Effects of Oxytocin Administrated During Cesarean Section, Signs of Myocardial Ischemia
NCT00781157PHASE4COMPLETEDPhenylephrine for Spinal Induced Hypotension
NCT00846651PHASE4COMPLETEDSpinal Anesthesia Induced Hypotension During Cesarean Section
NCT00922844PHASE4TERMINATEDThe Effect of Sevoflurane Versus Isoflurane on Vasopressor Need
NCT00991627PHASE4COMPLETEDDifferent Approaches to Maternal Hypotension During Cesarean Section
NCT00996190PHASE4COMPLETEDBest Regimen for Phenylephrine Administration During Cesarean Section
NCT01067391PHASE4COMPLETEDEffect of Tadalafil (Cialis) on the Cardiovascular System of Spinal Cord Injury (SCI) Males
NCT01414842PHASE4COMPLETEDHFR A-equilibrium on Cardiovascular Stability
NCT01415284PHASE4UNKNOWNED50 Determination of Hydroxyethylstarch for Treatment of Hypotension During Cesarean Section Under Spinal Anesthesia
NCT01418118PHASE4COMPLETEDAssessment of the Effects of Pressors on Graft Blood Flow After Free Tissue Transfer Surgery
NCT01481740PHASE4COMPLETEDPreventing Hypotension in Parturients With an Elevated Body Mass Index (BMI)
NCT01549223PHASE4COMPLETEDOxytocin And Uterotonic Agent Use For Cesarean Delivery
NCT02135146PHASE4COMPLETEDEvaluating Fluid Strategies in Thoracic Surgery Patients Utilizing a Goal Directed Approach
NCT02393196PHASE4UNKNOWNColloid Preload Versus Colloid Coload During Cesarean Deliveries
NCT02477501PHASE4COMPLETEDEphedrine vs. Nor Epinephrine Infusion in Preventing Hypotension After Spinal Anesthesia for Cesarean Section
NCT02737813PHASE4COMPLETEDCardiac Output Changes During Hyperbaric and Isobaric Bupivacaine in Patients Undergoing Cesarean Section
NCT02771158PHASE4WITHDRAWNMidodrine During Recovery From Septic Shock
NCT02802683PHASE4COMPLETEDHemodynamic Impact of Hyperbaric Versus Isobaric for Spinal Anesthesia During Cesarean Delivery
NCT02854787PHASE4COMPLETEDIntravenous Bolus of Phenylephrine vs. Norepinephrine in Preventing Hypotension After Spinal Anesthesia
NCT02913768PHASE4COMPLETEDReduction in Spinal-induced Hypotension With Ondansetron in Parturients Undergoing Caesarean Section
NCT02969239PHASE4UNKNOWNNorepinephrine and Phenylephrine for Maternal Cardiac Output During Spinal Anesthesia for Elective Cesarean Delivery
NCT03595319PHASE4UNKNOWNMedian Sevoflurane Concentration for Hypotension Between Young and Elderlypatients: Adaptive Clinical Trial
NCT03602014PHASE4COMPLETEDDose Response to the Norepinephrine Precursor Droxidopa in Hypotensive Individuals With Spinal Cord Injury
NCT03664037PHASE4COMPLETEDDexamethasone Blunts the Hypotensive Effect of Spinal Anesthesia in Geriatric Patients Undergoing Lower Limb Orthopedic Surgeries
NCT03704909PHASE4COMPLETEDManging Post Spinal Hypotension During Elective Cesarean Section
NCT03706755PHASE4COMPLETEDComparison of Two Doses of Norepinephrine in Preventing Hypotension After Spinal Anesthesia
NCT03973411PHASE4UNKNOWNOndansetron in the Prevention of Hypotension in Patients Undergoing Spinal Anesthesia
NCT04529005PHASE4COMPLETEDAngiotensin II in the Perioperative Management of Hypotension in Kidney Transplant Recipients
NCT04575675PHASE4COMPLETEDDapagliflozin on Hypotensive Heart Failure Patients After Sacubitril/Valsartan Therapy

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
NOREPINEPHRINE420
EPHEDRINE417
PHENYLEPHRINE417
DOPAMINE413
MIDODRINE410
ONDANSETRON49
VASOPRESSIN44
GRANISETRON43
LACTIC ACID43
BUPIVACAINE42
DOBUTAMINE42
DROXIDOPA42
EPINEPHRINE42
ISOFLURANE42
LEVOBUPIVACAINE42
OXYTOCIN42
PRILOCAINE42
RAMOSETRON42
TERLIPRESSIN42
ANGIOTENSIN II41
ARTICAINE41
ATROPINE41
CHLOROPROCAINE41
DAPAGLIFLOZIN41
DEFEROXAMINE41
DEXAMETHASONE PHOSPHORIC ACID41
DEXTROSE41
DROTRECOGIN ALFA (ACTIVATED)41
ESMOLOL41
FLUDROCORTISONE ACETATE41

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 71

This page pulls from 71 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncicd10cmicd11intactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot