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Atlas / Disease / Stroke disorder

Stroke disorder

disease
On this page

Also known as cerebrovascular accidentcerebrovascular accident, (CVA)CVACVA, cerebrovascular accidentstrokestroke syndromesyndrome, strokeundetermined stroke

Summary

Stroke disorder (MONDO:0005098) is a disease with 75 cohort genes (327 GWAS associations across 133 studies) and 5,951 clinical trials. Top therapeutic interventions include aspirin, alteplase, and tenecteplase.

At a glance

  • Cohort genes: 75
  • GWAS associations: 327
  • ClinVar variants: 9
  • Clinical trials: 5,951

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namestroke disorder
Mondo IDMONDO:0005098
EFOEFO:0000712
MeSHD020521
DOIDDOID:0051061
NCITC3390
SNOMED CT230690007
UMLSC0038454
MedGen52522
Anatomy (UBERON)UBERON:0003499
Is cancer (heuristic)no

Also known as: cerebrovascular accident · cerebrovascular accident, (CVA) · CVA · CVA, cerebrovascular accident · stroke · stroke syndrome · syndrome, stroke · undetermined stroke

Data availability: 9 ClinVar variants · 327 GWAS associations (133 studies) · 1 HPO phenotype · 3 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › cerebrovascular disorder › stroke disorder

Related subtypes (23): cerebral arteritis, intracranial thrombosis, occlusion precerebral artery, vascular dementia, internal carotid artery stenosis, carotid artery disorder, brain ischemia, brain infarction, cerebral amyloid angiopathy, vascular brain injury, basal ganglia cerebrovascular disorder, intracranial arterial disease, intracranial vasospasm, subclavian steal syndrome, pseudotumor cerebri, cerebral sinovenous thrombosis, HTRA1-related autosomal dominant cerebral small vessel disease, familial porencephaly, microangiopathy and leukoencephalopathy, pontine, autosomal dominant, cathepsin a-related arteriopathy-strokes-leukoencephalopathy, precerebral artery stenosis, cerebral artery stenosis, APP-related brain and vascular amyloidosis

Subtypes (4): large artery stroke, spinal cord ischemia, ischemic stroke, hemorrhagic stroke

Genetics & variants

GWAS landscape

327 GWAS associations across 133 studies. Top hits map to 30 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs562664641e-300ABCG5?
rs2476171e-149HERPUD1 - CETP?
rs60254e-137F5T2.93
rs9641842e-108ZPR1?
rs7800944e-91GCKR?
rs80828125e-67THEMIS3P - AKR1B1P6?
rs5295657e-63ABOC1.38
rs13330491e-56CDKN2B-AS1?
rs6293011e-49CELSR2?
rs7655472e-44LPL - RPL30P9?
rs348724713e-40TCF7L2C0.17
rs2613322e-35ALDH1A2, LIPC-AS1, LIPC?
rs17289181e-31PPM1G - NRBP1?
rs44448787e-28F11-AS1A1.23
rs1428273011e-27TCF7L2CTTCTTTCTTTCT0.16
rs40076423e-27CDKN2B-AS1T0.13
rs1745477e-25FADS1, FADS2?
rs17999631e-24F2A1.95
rs44206381e-22APOC1?
rs76325058e-22SEMA5B?
rs5623385e-21APOB - TDRD15?
rs70282683e-20CDKN2B-AS1A0.12
rs76540932e-19FGG - LRATT1.22
rs557304994e-19LPAT0.19
rs13330477e-19CDKN2B-AS1T0.06
rs29808533e-18TRIB1 - TRIB1AL?
rs6715e-18ALDH2A0.11
rs753257329e-18WDR70P1 - TM4SF4?
rs20747551e-17BAZ1B?
rs347131151e-17CDKN2B-AS1CTT0.11

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90042671Jiang L202161,995335,148A generalized linear mixed model association tool for biobank-scale data.
GCST90078258Backman JD202160,161359,437Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90042683Jiang L202160,152358,865A generalized linear mixed model association tool for biobank-scale data.
GCST90078273Backman JD202158,930364,757Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST007248Malik R201845,570775,530Genome-Wide Meta-analysis identifies three novel loci associated with stroke.
GCST009639Wang L201940,585406,111Additional common loci associated with stroke and obesity identified using pleiotropic analytical approach.
GCST005838Malik R201840,585406,111Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.
GCST006906Malik R201840,585406,111Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.
GCST90081457Backman JD202118,075272,229Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST007613Zhu Z201912,55046,368Genetic overlap of chronic obstructive pulmonary disease and cardiovascular disease-related traits: a large-scale genome-wide cross-trait analysis.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding3
Tier 2: splice/UTR3
Tier 3: regulatory2
Tier 4: intronic/intergenic42

MAF distribution

BucketVariants
common (>=0.05)47
low_freq (0.01-0.05)2
rare (<0.01)1
unknown0

Functional consequences

ConsequenceCount
intron_variant30
intergenic_variant10
missense_variant3
3_prime_UTR_variant3
non_coding_transcript_exon_variant2
regulatory_region_variant2

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs56266464243827852G>A,C0.05intron_variantABCG51e-300Tier 4: intronic/intergenic
rs2476171656956804C>A0.05intergenic_variantHERPUD1 - CETP1e-149Tier 4: intronic/intergenic
rs60251169549811C>A,G,T0.025missense_variantF54e-137Tier 1: coding
rs96418411116778201G>C0.053_prime_UTR_variantZPR12e-108Tier 2: splice/UTR
rs780094227518370T>A,C,G0.05intron_variantGCKR4e-91Tier 4: intronic/intergenic
rs8082812188522684C>A0.05intergenic_variantTHEMIS3P - AKR1B1P65e-67Tier 4: intronic/intergenic
rs5295659133274084C>A,G,T0.341intron_variantABO7e-63Tier 4: intronic/intergenic
rs1333049922125504G>A,C0.05intergenic_variantCDKN2B-AS11e-56Tier 4: intronic/intergenic
rs6293011109275684G>A,C,T0.053_prime_UTR_variantCELSR21e-49Tier 2: splice/UTR
rs765547820008763G>A,C,T0.05intergenic_variantLPL - RPL30P92e-44Tier 4: intronic/intergenic
rs3487247110112994312T>C0.291intron_variantTCF7L23e-40Tier 4: intronic/intergenic
rs2613321558435126A>G0.05non_coding_transcript_exon_variantALDH1A2, LIPC-AS1, LIPC2e-35Tier 4: intronic/intergenic
rs1728918227412596A>C,G,T0.05intron_variantPPM1G - NRBP11e-31Tier 4: intronic/intergenic
rs44448784186292729C>A,G,T0.401intron_variantF11-AS17e-28Tier 4: intronic/intergenic
rs142827301101130366660.207intron_variantTCF7L21e-27Tier 4: intronic/intergenic
rs4007642922093300A>C,T0.484intron_variantCDKN2B-AS13e-27Tier 4: intronic/intergenic
rs1745471161803311T>C0.05intron_variantFADS1, FADS27e-25Tier 4: intronic/intergenic
rs17999631146739505G>A0.0153_prime_UTR_variantF21e-24Tier 2: splice/UTR
rs44206381944919689A>G0.05intergenic_variantAPOC11e-22Tier 4: intronic/intergenic
rs76325053123019460A>G0.05intron_variantSEMA5B8e-22Tier 4: intronic/intergenic
rs562338221065449A>C,G,T0.05intron_variantAPOB - TDRD155e-21Tier 4: intronic/intergenic
rs7028268922048415G>A,C0.371intron_variantCDKN2B-AS13e-20Tier 4: intronic/intergenic
rs76540934154623920A>T0.232intergenic_variantFGG - LRAT2e-19Tier 4: intronic/intergenic
rs557304996160584578C>T0.082intron_variantLPA4e-19Tier 4: intronic/intergenic
rs1333047922124505A>C,G,T0.481intergenic_variantCDKN2B-AS17e-19Tier 4: intronic/intergenic
rs29808538125466108A>C0.05intergenic_variantTRIB1 - TRIB1AL3e-18Tier 4: intronic/intergenic
rs67112111803962G>A0.238missense_variantALDH25e-18Tier 1: coding
rs753257323149472926A>G0.05regulatory_region_variantWDR70P1 - TM4SF49e-18Tier 3: regulatory
rs2074755773462836T>A,C,G0.05intron_variantBAZ1B1e-17Tier 4: intronic/intergenic
rs34713115922049484C>CTT,CTTTCTGCACACTGCATAAAGAGTCCTAAAAGACTCTT0.431intron_variantCDKN2B-AS11e-17Tier 4: intronic/intergenic

ClinVar germline variants

9 retrieved; paginated sample, class counts are floors:

4 pathogenic, 2 likely pathogenic, 2 uncertain significance, 1 likely benign

ClinVarVariant (HGVS)GeneClassificationReview
9589NC_012920.1(MT-TL1):m.3243A>GMT-TL1Pathogenicreviewed by expert panel
585600NM_000435.3(NOTCH3):c.227G>A (p.Cys76Tyr)NOTCH3Pathogeniccriteria provided, single submitter
9219NM_000435.3(NOTCH3):c.505C>T (p.Arg169Cys)NOTCH3Pathogeniccriteria provided, multiple submitters, no conflicts
13653NM_006218.4(PIK3CA):c.3140A>T (p.His1047Leu)PIK3CAPathogeniccriteria provided, multiple submitters, no conflicts
812744NM_000435.3(NOTCH3):c.1136G>C (p.Cys379Ser)NOTCH3Likely pathogeniccriteria provided, single submitter
1804036NM_001256071.3(RNF213):c.114C>G (p.Asn38Lys)RNF213Likely pathogeniccriteria provided, single submitter
374128NM_016203.4(PRKAG2):c.590C>G (p.Pro197Arg)PRKAG2Uncertain significancecriteria provided, multiple submitters, no conflicts
523426NM_001256071.3(RNF213):c.11659A>G (p.Lys3887Glu)RNF213Uncertain significancecriteria provided, single submitter
805948NC_012920.1(MT-ND4):m.12015T>CMT-ND4Likely benigncriteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 64 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
RUNX1Orphanet:102724Acute myeloid leukemia with t(8;21)(q22;q22) translocation
RUNX1Orphanet:521Chronic myeloid leukemia
RUNX1Orphanet:71290Familial platelet disorder with associated myeloid malignancy
RUNX1Orphanet:98850Aggressive systemic mastocytosis
SEMA3AOrphanet:130Brugada syndrome
SEMA3AOrphanet:478Kallmann syndrome
SLC7A7Orphanet:470Lysinuric protein intolerance
SMARCA4Orphanet:1465Coffin-Siris syndrome
SMARCA4Orphanet:231108Rhabdoid tumor predisposition syndrome
SMARCA4Orphanet:370396Small cell carcinoma of the ovary
SMARCA4Orphanet:466962SMARCA4-deficient sarcoma of thorax
SPARCOrphanet:216820Osteogenesis imperfecta type 4
SPI1Orphanet:33110Autosomal non-syndromic agammaglobulinemia
SPINK2Orphanet:399805Male infertility with azoospermia or oligozoospermia due to single gene mutation
HNF1AOrphanet:319303Chromophobe renal cell carcinoma
HNF1AOrphanet:324575Hyperinsulinism due to HNF1A deficiency
HNF1AOrphanet:404511Clear cell papillary renal cell carcinoma
HNF1AOrphanet:552MODY
TGFBIOrphanet:98956Epithelial basement membrane dystrophy
TGFBIOrphanet:98960Thiel-Behnke corneal dystrophy
TGFBIOrphanet:98961Reis-Bücklers corneal dystrophy
TGFBIOrphanet:98962Granular corneal dystrophy type I
TGFBIOrphanet:98963Granular corneal dystrophy type II
TGFBIOrphanet:98964Lattice corneal dystrophy type I
UQCRFS1Orphanet:1460Isolated complex III deficiency
XKOrphanet:59306McLeod neuroacanthocytosis syndrome
RNF213Orphanet:2573Moyamoya disease
WNK1Orphanet:88940Pseudohypoaldosteronism type 2C
WNK1Orphanet:970Hereditary sensory and autonomic neuropathy type 2
NINOrphanet:319675Microcephalic primordial dwarfism, Dauber type
NINOrphanet:808Seckel syndrome
IL36RNOrphanet:163927Pustulosis palmaris et plantaris
IL36RNOrphanet:163931Acrodermatitis continua of Hallopeau
IL36RNOrphanet:247353Generalized pustular psoriasis
IL36RNOrphanet:404546DITRA
SFXN4Orphanet:391348Growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome
PARK7Orphanet:2828Young-onset Parkinson disease
PARK7Orphanet:90020Parkinson-dementia complex of Guam
CPAPOrphanet:2512Autosomal recessive primary microcephaly
CPAPOrphanet:808Seckel syndrome
CHD3Orphanet:599082CHD3-related developmental delay-speech delay-intellectual disability-abnormalities of vision-facial dysmorphism syndrome
SLC39A13Orphanet:157965SLC39A13-related spondylodysplastic Ehlers-Danlos syndrome
PHACTR1Orphanet:697160Infantile epileptic spasms syndrome
ADAMTS2Orphanet:1901Dermatosparaxis Ehlers-Danlos syndrome
COL4A1Orphanet:36383COL4A1/2-related familial vascular leukoencephalopathy
COL4A1Orphanet:477749Pontine autosomal dominant microangiopathy with leukoencephalopathy
COL4A1Orphanet:481986Familial schizencephaly
COL4A1Orphanet:73229HANAC syndrome
COL4A1Orphanet:75326Familial isolated retinal arteriolar tortuosity
COL4A1Orphanet:899Walker-Warburg syndrome

Cohort genes → proteins

75 cohort genes, 74 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only74
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
RUNX1HGNC:10471ENSG00000159216Q01196Runt-related transcription factor 1gwas
SEMA3AHGNC:10723ENSG00000075213Q14563Semaphorin-3Agwas
SLC22A3HGNC:10967ENSG00000146477O75751Solute carrier family 22 member 3gwas
SLC7A7HGNC:11065ENSG00000155465Q9UM01Y+L amino acid transporter 1gwas
SMARCA4HGNC:11100ENSG00000127616P51532SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4gwas
SORT1HGNC:11186ENSG00000134243Q99523Sortilingwas
SPARCHGNC:11219ENSG00000113140P09486SPARCgwas
SPI1HGNC:11241ENSG00000066336P17947Transcription factor PU.1gwas
SPINK2HGNC:11245ENSG00000128040P20155Serine protease inhibitor Kazal-type 2gwas
SUPT3HHGNC:11466ENSG00000196284O75486Transcription initiation protein SPT3 homologgwas
HNF1AHGNC:11621ENSG00000135100P20823Hepatocyte nuclear factor 1-alphagwas
TCF21HGNC:11632ENSG00000118526O43680Transcription factor 21gwas
TGFBIHGNC:11771ENSG00000120708Q15582Transforming growth factor-beta-induced protein ig-h3gwas
UQCRFS1HGNC:12587ENSG00000169021P47985Cytochrome b-c1 complex subunit Rieske, mitochondrialgwas
UVRAGHGNC:12640ENSG00000198382Q9P2Y5UV radiation resistance-associated gene proteingwas
XKHGNC:12811ENSG00000047597P51811Endoplasmic reticulum membrane adapter protein XKgwas
ZBTB14HGNC:12860ENSG00000198081O43829Zinc finger and BTB domain-containing protein 14gwas
ZNF160HGNC:12948ENSG00000170949Q9HCG1Zinc finger protein 160gwas
HDAC9HGNC:14065ENSG00000048052Q9UKV0Histone deacetylase 9gwas
WDR12HGNC:14098ENSG00000138442Q9GZL7Ribosome biogenesis protein WDR12gwas
ICA1LHGNC:14442ENSG00000163596Q8NDH6Islet cell autoantigen 1-like proteingwas
RNF213HGNC:14539ENSG00000173821Q63HN8E3 ubiquitin-protein ligase RNF213clinvar
WNK1HGNC:14540ENSG00000060237Q9H4A3Serine/threonine-protein kinase WNK1gwas
LRP10HGNC:14553ENSG00000197324Q7Z4F1Low-density lipoprotein receptor-related protein 10gwas
ADAMTS12HGNC:14605ENSG00000151388P58397A disintegrin and metalloproteinase with thrombospondin motifs 12gwas
NINHGNC:14906ENSG00000100503Q8N4C6Nineingwas
WFDC1HGNC:15466ENSG00000103175Q9HC57WAP four-disulfide core domain protein 1gwas
ALDH1A2HGNC:15472ENSG00000128918O94788Retinal dehydrogenase 2gwas
IL1F10HGNC:15552ENSG00000136697Q8WWZ1Interleukin-1 family member 10gwas
IL36RNHGNC:15561ENSG00000136695Q9UBH0Interleukin-36 receptor antagonist proteingwas
ULK4HGNC:15784ENSG00000168038Q96C45Serine/threonine-protein kinase ULK4gwas
RASD1HGNC:15828ENSG00000108551Q9Y272Dexamethasone-induced Ras-related protein 1gwas
ABCC13HGNC:16022ENSG00000243064ATP binding cassette subfamily C member 13 (pseudogene)gwas
SFXN4HGNC:16088ENSG00000183605Q6P4A7Sideroflexin-4gwas
PARK7HGNC:16369ENSG00000116288Q99497Parkinson disease protein 7gwas
DAPP1HGNC:16500ENSG00000070190Q9UN19Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositidegwas
MRPL52HGNC:16655ENSG00000172590Q86TS9Large ribosomal subunit protein mL52gwas
CPAPHGNC:17272ENSG00000151849Q9HC77Centrosomal P4.1-associated proteingwas
TRIM29HGNC:17274ENSG00000137699Q14134Tripartite motif-containing protein 29gwas
SLC44A2HGNC:17292ENSG00000129353Q8IWA5Choline transporter-like protein 2gwas
CDC5LHGNC:1743ENSG00000096401Q99459Cell division cycle 5-like proteingwas
TSPAN5HGNC:17753ENSG00000168785P62079Tetraspanin-5gwas
ERRFI1HGNC:18185ENSG00000116285Q9UJM3ERBB receptor feedback inhibitor 1gwas
BTBD7HGNC:18269ENSG00000011114Q9P203BTB/POZ domain-containing protein 7gwas
KCNG3HGNC:18306ENSG00000171126Q8TAE7Voltage-gated potassium channel regulatory subunit KCNG3gwas
GTSCR1HGNC:18406ENSG00000263417Q86UQ5Gilles de la Tourette syndrome chromosomal region candidate gene 1 proteingwas
CHD3HGNC:1918ENSG00000170004Q12873ATP-dependent chromatin remodeler CHD3gwas
RBM23HGNC:20155ENSG00000100461Q86U06Probable RNA-binding protein 23gwas
REM2HGNC:20248ENSG00000139890Q8IYK8GTP-binding protein REM 2gwas
CLDN17HGNC:2038ENSG00000156282P56750Claudin-17gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
RUNX1Runt-related transcription factor 1Forms the heterodimeric complex core-binding factor (CBF) with CBFB.
SEMA3ASemaphorin-3AInvolved in the development of the olfactory system and in neuronal control of puberty.
SLC22A3Solute carrier family 22 member 3Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics.
SLC7A7Y+L amino acid transporter 1Heterodimer with SLC3A2, that functions as an antiporter which operates as an efflux route by exporting cationic amino acids from inside the cells in exchange with neutral amino acids plus sodium ions and may participate in nitric oxide sy…
SMARCA4SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
SORT1SortilinFunctions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface.
SPARCSPARCAppears to regulate cell growth through interactions with the extracellular matrix and cytokines.
SPI1Transcription factor PU.1Pioneer transcription factor, which controls hematopoietic cell fate by decompacting stem cell heterochromatin and allowing other transcription factors to enter otherwise inaccessible genomic sites.
SPINK2Serine protease inhibitor Kazal-type 2As a strong inhibitor of acrosin, it is required for normal spermiogenesis.
SUPT3HTranscription initiation protein SPT3 homologProbable transcriptional activator.
HNF1AHepatocyte nuclear factor 1-alphaTranscriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver.
TCF21Transcription factor 21Involved in epithelial-mesenchymal interactions in kidney and lung morphogenesis that include epithelial differentiation and branching morphogenesis.
TGFBITransforming growth factor-beta-induced protein ig-h3Plays a role in cell adhesion.
UQCRFS1Cytochrome b-c1 complex subunit Rieske, mitochondrialComponent of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation.
UVRAGUV radiation resistance-associated gene proteinVersatile protein that is involved in regulation of different cellular pathways implicated in membrane trafficking.
XKEndoplasmic reticulum membrane adapter protein XKRecruits the lipid transfer protein VPS13A from lipid droplets to the endoplasmic reticulum (ER) membrane.
ZBTB14Zinc finger and BTB domain-containing protein 14Transcriptional activator of the dopamine transporter (DAT), binding its promoter at the consensus sequence 5’-CCTGCACAGTTCACGGA-3'.
ZNF160Zinc finger protein 160May be involved in transcriptional regulation.
HDAC9Histone deacetylase 9Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
WDR12Ribosome biogenesis protein WDR12Component of the PeBoW complex, which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome.
RNF213E3 ubiquitin-protein ligase RNF213Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity.
WNK1Serine/threonine-protein kinase WNK1Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx.
LRP10Low-density lipoprotein receptor-related protein 10Probable receptor, which is involved in the internalization of lipophilic molecules and/or signal transduction.
ADAMTS12A disintegrin and metalloproteinase with thrombospondin motifs 12Metalloprotease that may play a role in the degradation of COMP.
NINNineinCentrosomal protein required in the positioning and anchorage of the microtubule minus-end in epithelial cells.
WFDC1WAP four-disulfide core domain protein 1Has growth inhibitory activity.
ALDH1A2Retinal dehydrogenase 2Catalyzes the NAD-dependent oxidation of aldehyde substrates, such as all-trans-retinal and all-trans-13,14-dihydroretinal, to their corresponding carboxylic acids, all-trans-retinoate and all-trans-13,14-dihydroretinoate, respectively.
IL1F10Interleukin-1 family member 10Cytokine with immunomodulatory activity.
IL36RNInterleukin-36 receptor antagonist proteinInhibits the activity of interleukin-36 (IL36A,IL36B and IL36G) by binding to receptor IL1RL2 and preventing its association with the coreceptor IL1RAP for signaling.
ULK4Serine/threonine-protein kinase ULK4May be involved in the remodeling of cytoskeletal components, such as alpha-tubulin, and in this way regulates neurite branching and elongation, as well as cell motility.
RASD1Dexamethasone-induced Ras-related protein 1Small GTPase.
SFXN4Sideroflexin-4Mitochondrial amino-acid transporter.
PARK7Parkinson disease protein 7Multifunctional protein with controversial molecular function which plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease.
DAPP1Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositideMay act as a B-cell-associated adapter that regulates B-cell antigen receptor (BCR)-signaling downstream of PI3K.
CPAPCentrosomal P4.1-associated proteinPlays an important role in cell division and centrosome function by participating in centriole duplication.
TRIM29Tripartite motif-containing protein 29Plays a crucial role in the regulation of macrophage activation in response to viral or bacterial infections within the respiratory tract.
SLC44A2Choline transporter-like protein 2Choline/H+ antiporter, mainly in mitochondria.
CDC5LCell division cycle 5-like proteinDNA-binding protein involved in cell cycle control.
TSPAN5Tetraspanin-5Part of TspanC8 subgroup, composed of 6 members that interact with the transmembrane metalloprotease ADAM10.
ERRFI1ERBB receptor feedback inhibitor 1Negative regulator of EGFR signaling in skin morphogenesis.
BTBD7BTB/POZ domain-containing protein 7Acts as a mediator of epithelial dynamics and organ branching by promoting cleft progression.
KCNG3Voltage-gated potassium channel regulatory subunit KCNG3Regulatory subunit of the voltage-gated potassium (Kv) channel which, when coassembled with KCNB1, modulates the kinetics parameters of the heterotetrameric channel namely the inactivation and deactivation rate.
CHD3ATP-dependent chromatin remodeler CHD3ATP-dependent chromatin-remodeling factor that binds and distorts nucleosomal DNA.
RBM23Probable RNA-binding protein 23RNA-binding protein that acts both as a transcription coactivator and pre-mRNA splicing factor.
REM2GTP-binding protein REM 2Binds GTP saturably and exhibits a low intrinsic rate of GTP hydrolysis.
CLDN17Claudin-17Channel-forming tight junction protein with selectivity for anions, including chloride and hydrogencarbonate, and for solutes smaller than 9 Angstrom in diameter.
ADGRL4Adhesion G protein-coupled receptor L4Endothelial orphan receptor that acts as a key regulator of angiogenesis.
SLC39A13Zinc transporter ZIP13Functions as a zinc transporter transporting Zn(2+) from the Golgi apparatus to the cytosol and thus influences the zinc level at least in areas of the cytosol.
FOXQ1Forkhead box protein Q1Plays a role in hair follicle differentiation.
PHACTR1Phosphatase and actin regulator 1Binds actin monomers (G actin) and plays a role in multiple processes including the regulation of actin cytoskeleton dynamics, actin stress fibers formation, cell motility and survival, formation of tubules by endothelial cells, and regula…

Protein-family classification

Druggable: 17 · Difficult: 19 · Unknown: 39 · Druggable fraction: 0.23

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
Transcription factor141.5×0.647
Protease41.9×0.745
Transporter22.1×0.836
Ion channel11.5×0.852
Scaffold/PPI51.1×0.852
Kinase31.1×0.852
Other/Unknown390.9×0.960
Enzyme (other)50.8×0.960
Antibody/Immunoglobulin10.4×0.960
GPCR10.3×0.960

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
RUNX1Transcription factornoAML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
SEMA3AAntibody/ImmunoglobulinyesSemap_dom, Ig_sub, Ig-like_dom
SLC22A3TransporteryesOrgcat_transp/SVOP, Sugar_transporter_CS, MFS
SLC7A7TransporteryesAA/rel_permease1, AminoAcid_Transporter
SMARCA4Other/UnknownnoSNF2_N, Bromodomain, Helicase_C-like
SORT1Scaffold/PPInoVPS10, WD40/YVTN_repeat-like_dom_sf, Sortilin_C
SPARCOther/UnknownnoOsteonectin_CS, Kazal_dom, Fol_N
SPI1Other/UnknownnoEts_dom, WH-like_DNA-bd_sf, WH_DNA-bd_sf
SPINK2Other/UnknownnoKazal_dom, Kazal_dom_sf, SPINK2
SUPT3HOther/UnknownnoTFIID_TAF13, Histone-fold
HNF1ATranscription factornoHD, HNF1b_C, HNF1a_C
TCF21Transcription factornobHLH_dom, HLH_DNA-bd_sf, E-box_TF_Regulators
TGFBIOther/UnknownnoFAS1_domain, EMI_domain, TGFBI/POSTN
UQCRFS1Other/UnknownnoRieske_TM, Rieske_Fe-S_prot_C, Ubiquinol_cyt_c_Rdtase_Fe-S-su
UVRAGEnzyme (other)yes2.7.1.137C2_dom, UV_resistance/autophagy_Atg14, C2_domain_sf
XKOther/UnknownnoXK-rel, XK-related_adapter
ZBTB14Transcription factornoBTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
ZNF160Transcription factornoKRAB, Znf_C2H2_type, KRAB_dom_sf
HDAC9Enzyme (other)yes3.5.1.98HDACs, Ureohydrolase_dom_sf, His_deacetylse_dom
WDR12Scaffold/PPInoWD40_rpt, NLE, WD40/YVTN_repeat-like_dom_sf
ICA1LScaffold/PPInoIslet_autoAg_Ica1_C, AH_dom, Islet_autoAg_Ica1/Ica1-like
RNF213Transcription factornoZnf_RING, AAA+_ATPase, Znf_RING/FYVE/PHD
WNK1KinaseyesProt_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
LRP10Other/UnknownnoCUB_dom, LDrepeatLR_classA_rpt, LDLR_class-A_CS
ADAMTS12ProteaseyesTSP1_rpt, Peptidase_M12B, Peptidase_M12B_N
NINOther/UnknownnoEF_hand_dom, EF-hand-dom_pair
WFDC1Other/UnknownnoWAP_dom, Elafin-like_sf, WFDC1
ALDH1A2Enzyme (other)yes1.2.1.36Aldehyde_DH_dom, Ald_DH_CS_CYS, Ald_DH/histidinol_DH
IL1F10Other/UnknownnoIL-1_fam, IL-1RA/IL-36, IL1/FGF
IL36RNOther/UnknownnoIL-1_fam, IL-1RA/IL-36, IL1/FGF
ULK4KinaseyesProt_kinase_dom, Kinase-like_dom_sf, ARM-like
RASD1Other/UnknownnoSmall_GTPase, Small_GTP-bd, P-loop_NTPase
ABCC13Other/Unknownno
SFXN4Other/UnknownnoMtc
PARK7Enzyme (other)yes3.5.1.124DJ-1/PfpI, DJ-1, Class_I_gatase-like
DAPP1Scaffold/PPInoSH2, PH_domain, PH-like_dom_sf
MRPL52Other/UnknownnoRibosomal_mL52
CPAPOther/UnknownnoCENPJ_C_dom, TCP10L/CENPJ, Tcp10_C_sf
TRIM29Transcription factornoZnf_B-box, E3_ubiq-ligase_TRIM/RNF, TRIM8/14/16/25/29/45/65_CC
SLC44A2Other/UnknownnoCholine_transptr-like
CDC5LTranscription factornoSANT/Myb, Homeodomain-like_sf, Myb_dom
TSPAN5Other/UnknownnoTetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin
ERRFI1KinaseyesCdc42-bd-like, EGFR_SigReg_Kinase
BTBD7Other/UnknownnoBTB/POZ_dom, SKP1/BTB/POZ_sf, BACK
KCNG3Ion channelyesBTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv
GTSCR1Other/Unknownno
CHD3Transcription factornoSNF2_N, Chromo/chromo_shadow_dom, Helicase_C-like
RBM23Other/UnknownnoRRM_dom, RBM39_SF, Nucleotide-bd_a/b_plait_sf
REM2Enzyme (other)yes3.4.23.15Small_GTPase, Sigma_54_int_dom_ATP-bd_1, P-loop_NTPase
CLDN17Other/UnknownnoPMP22/EMP/MP20/Claudin, Claudin, Claudin_CS

Expression context

Cohort genes with no expression data: 0.

64 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)75
unknown0

Top tissues across cohort

TissueCohort genes
sperm8
cortical plate7
secondary oocyte6
primordial germ cell in gonad6
stromal cell of endometrium5
mucosa of transverse colon5
ganglionic eminence4
granulocyte4
male germ line stem cell (sensu Vertebrata) in testis4
amniotic fluid4
adrenal tissue4
calcaneal tendon4
endothelial cell4
buccal mucosa cell4
apex of heart4
monocyte3
right lobe of liver3
right lung3
pericardium3
corpus callosum3

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
RUNX1253ubiquitousmarkerolfactory segment of nasal mucosa, epithelium of bronchus, mucosa of paranasal sinus
SEMA3A194ubiquitousmarkerstromal cell of endometrium, cortical plate, colonic epithelium
SLC22A3189broadmarkerthoracic aorta, ascending aorta, descending thoracic aorta
SLC7A7215ubiquitousmarkersecondary oocyte, monocyte, mononuclear cell
SMARCA4295ubiquitousmarkerganglionic eminence, cortical plate, cervix squamous epithelium
SORT1291ubiquitousmarkerinferior vagus X ganglion, corpus epididymis, subthalamic nucleus
SPARC306ubiquitousmarkertibia, stromal cell of endometrium, periodontal ligament
SPI1170broadmarkergranulocyte, monocyte, leukocyte
SPINK2177broadmarkercorpus epididymis, cauda epididymis, seminal vesicle
SUPT3H206ubiquitousyesprimordial germ cell in gonad, sperm, male germ line stem cell (sensu Vertebrata) in testis
HNF1A81tissue_specificyesright lobe of liver, mucosa of transverse colon, liver
TCF21175broadmarkerprimordial germ cell in gonad, right lung, upper lobe of left lung
TGFBI278ubiquitousmarkeramniotic fluid, synovial joint, pericardium
UQCRFS1134ubiquitousmarkergastrocnemius, heart left ventricle, mucosa of transverse colon
UVRAG279ubiquitousmarkeradrenal tissue, corpus callosum, calcaneal tendon
XK221broadmarkertrabecular bone tissue, jejunal mucosa, colonic mucosa
ZBTB14240ubiquitousyescalcaneal tendon, tendon, lymph node
ZNF160294ubiquitousmarkerrenal medulla, endothelial cell, pylorus
HDAC9277ubiquitousmarkeroocyte, monocyte, secondary oocyte
WDR12288ubiquitousmarkerventricular zone, ganglionic eminence, cortical plate
ICA1L244ubiquitousmarkerbronchial epithelial cell, bronchus, Brodmann (1909) area 23
RNF213252ubiquitousmarkergranulocyte, metanephros cortex, pancreatic ductal cell
WNK1297ubiquitousmarkermedial globus pallidus, globus pallidus, inferior vagus X ganglion
LRP10284ubiquitousmarkerstromal cell of endometrium, decidua, right coronary artery
ADAMTS12170broadmarkeradrenal tissue, male germ line stem cell (sensu Vertebrata) in testis, stromal cell of endometrium
NIN253ubiquitousmarkeroviduct epithelium, buccal mucosa cell, cardiac muscle of right atrium
WFDC1241broadmarkersaphenous vein, right coronary artery, seminal vesicle
ALDH1A2226broadmarkergerminal epithelium of ovary, decidua, sperm
IL1F1032yesskin of leg, zone of skin, skin of abdomen
IL36RN106tissue_specificyesamniotic fluid, upper arm skin, gingiva

Protein interactions among cohort

Intra-cohort edges: 23.

Hub genes (top 10 by interactor count)

SymbolInteractor count
SMARCA48,138
CDC5L5,930
PARK75,722
CHD35,202
RUNX14,994
ALDH1A24,289
UQCRFS14,001
SPI13,823
WDR123,702
RASD13,278

Intra-cohort edges

ABSources
ADAMTS12ADAMTS7string_interaction
ADAMTS7PHACTR1string_interaction
ADAMTS7SORT1string_interaction
ALDH1A2TCF21string_interaction
COL4A1TGFBIstring_interaction
COX7A2LUQCRFS1intact, string_interaction
CTTNBP2NLSPINK2biogrid_interaction
HDAC9SMARCA4string_interaction
HDAC9WNK1intact
HNF1AZBTB14string_interaction
ICA1LNBEAL1string_interaction
ICA1LWDR12string_interaction
ICA1LZCCHC14string_interaction
MARS2UQCRFS1intact
MICAL2PHACTR1string_interaction
NBEAL1WDR12string_interaction
NKX2-5SMARCA4string_interaction
NKX2-5TCF21string_interaction
PHACTR1SORT1string_interaction
PHACTR1WDR12string_interaction
RUNX1SPI1biogrid_interaction, string_interaction
SLC44A2TSPAN15string_interaction
TSPAN15TSPAN5intact

Structural data

PDB: 36 · AlphaFold-only: 38 · No structure: 1

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
PARK7Q9949788
MRPL52Q86TS973
CDC5LQ9945937
SPI1P1794735
SMARCA4P5153231
SORT1Q9952317
TGFBIQ1558210
ALDH1A2O947887
ERRFI1Q9UJM37
HNF1AP208236
CPAPQ9HC776
PHACTR1Q9C0D06
RUNX1Q011965
SLC7A7Q9UM015
UQCRFS1P479855
WNK1Q9H4A35
MICAL2O948515
SPARCP094864
SUPT3HO754864
RNF213Q63HN84
COL4A1P024624
NKX2-5P529524
SLC22A3O757513
UVRAGQ9P2Y53
WDR12Q9GZL73
IL36RNQ9UBH03
TSPAN15O958583
SPINK2P201552
HDAC9Q9UKV02
ULK4Q96C452

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
FAR2Q96K1294.15
ADTRPQ96IZ290.99
KLHL32Q96NJ590.01
MARS2Q96GW989.66
TSPAN5P6207989.48
SFXN4Q6P4A785.33
SEMA3AQ1456384.50
SLC44A2Q8IWA583.62
LPAL2Q1660982.18
XKP5181181.89
RASD1Q9Y27280.75
KCNG3Q8TAE780.07
COX7A2LO1454879.89
CLDN17P5675077.86
SLC39A13Q96H7276.33
NBEAL1Q6ZS3075.20
NANOS3P6032371.75
ADAMTS2O9545071.59
RFTN2Q52LD869.19
ZNF160Q9HCG168.98
ICA1LQ8NDH668.89
WFDC1Q9HC5768.08
LRP10Q7Z4F167.84
CTTNBP2NLQ9P2B467.43
TCF21O4368066.67
ADAMTS12P5839764.56
NINQ8N4C664.47
ADAMTS7Q9UKP464.26
CDKN2AIPQ9NXV663.54
CHD3Q1287363.21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 495. Enrichment computed across 139 evidence-associated genes (85 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 85 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Defective F8 cleavage by thrombin289.6×0.067F2, F8
Chylomicron clearance253.7×0.067LDLR, LIPC
Amplification and propagation of coagulation cascade322.4×0.067F2, F5, F8
Regulation of clotting cascade411.0×0.067F2, F5, F8, PROCR
Initiation of coagulation cascade316.8×0.071F2, F5, F8
Interleukin-36 pathway238.4×0.093IL1F10, IL36RN
R-HSA-140837233.6×0.105F2, KNG1
Defective B3GALTL causes PpS310.9×0.116ADAMTS12, ADAMTS2, ADAMTS7
O-glycosylation of TSR domain-containing proteins310.6×0.116ADAMTS12, ADAMTS2, ADAMTS7
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)46.9×0.116SMARCA4, HDAC9, CHD3, GATA3
Respiratory electron transport55.6×0.116UQCRFS1, SFXN4, COX7A2L, MT-ND4, COXFA4
Platelet degranulation55.2×0.116SPARC, F5, F8, FGG, KNG1
R-HSA-140877222.4×0.131F2, KNG1
Fibrin formation220.7×0.143F2, FGG
Gamma-carboxylation, transport, and amino-terminal cleavage of proteins1134.3×0.160F2
Defective factor VIII causes hemophilia A1134.3×0.160F2
Defective F8 accelerates dissociation of the A2 domain1134.3×0.160F8
Defective F8 binding to the cell membrane1134.3×0.160F8
Defective F8 secretion1134.3×0.160F8
SLC-mediated transport of organic cations217.9×0.160RUNX1, SLC22A3
R-HSA-549132217.9×0.160RUNX1, SLC22A3
Plasma lipoprotein assembly, remodeling, and clearance38.1×0.160LDLR, LIPC, LPA
Diseases associated with O-glycosylation of proteins37.6×0.160ADAMTS12, ADAMTS2, ADAMTS7
Metabolism of serotonin167.2×0.244ALDH2
Transport of glycerol from adipocytes to the liver by Aquaporins167.2×0.244AQP7
Defective amino acid transport by SLC7A7 causes lysinuric protein intolerance (LPI)167.2×0.244SLC7A7
Defective F8 binding to von Willebrand factor167.2×0.244F8
RUNX3 regulates RUNX1-mediated transcription144.8×0.244RUNX1
R-HSA-9651496144.8×0.244F2
Defective factor IX causes thrombophilia144.8×0.244F8

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 119 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
pro-T cell differentiation2141.6×0.023SPI1, GATA3
myeloid leukocyte differentiation294.4×0.023RUNX1, SPI1
pulmonary myocardium development294.4×0.023NKX2-5, PITX2
regulation of membrane protein ectodomain proteolysis294.4×0.023TSPAN5, TSPAN15
negative regulation of platelet aggregation335.4×0.023SH2B3, UBASH3B, PRKG1
negative regulation of blood coagulation330.4×0.023ADTRP, F2, KNG1
blood coagulation68.8×0.023F2, F5, F8, AP3B1, KNG1, PROCR
ureter maturation270.8×0.041ALDH1A2, GATA3
regulation of cardiac muscle cell proliferation256.6×0.054RUNX1, NKX2-5
extracellular matrix organization66.2×0.054TGFBI, ADAMTS12, ADAMTS2, ADAMTS7, FOXF2, MMP14
embryonic heart tube left/right pattern formation247.2×0.059NKX2-5, PITX2
negative regulation of leukocyte cell-cell adhesion247.2×0.059WNK1, ADTRP
chondrocyte differentiation410.1×0.059RUNX1, TGFBI, ADAMTS12, ADAMTS7
positive regulation of miRNA transcription49.8×0.059SMARCA4, SPI1, GATA3, NOTCH3
type IV hypersensitivity1141.6×0.080GATA3
positive regulation of acute inflammatory response to antigenic stimulus1141.6×0.080PARK7
Purkinje myocyte differentiation1141.6×0.080NKX2-5
septum secundum development1141.6×0.080NKX2-5
determination of bilateral symmetry1141.6×0.080ALDH1A2
response to muscle inactivity1141.6×0.080PIK3CA
nitroglycerin metabolic process1141.6×0.080ALDH2
subthalamic nucleus development1141.6×0.080PITX2
astral microtubule nucleation1141.6×0.080CPAP
negative regulation of transporter activity1141.6×0.080CTTNBP2NL
intermediate-density lipoprotein particle remodeling1141.6×0.080LIPC
cellular response to glyoxal1141.6×0.080PARK7
protein kinase C deactivation1141.6×0.080ULK4
host-mediated perturbation of viral transcription1141.6×0.080PSMC3
glycolate biosynthetic process1141.6×0.080PARK7
detoxification of mercury ion1141.6×0.080PARK7

Therapeutics

Drugs indicated for this disease

18 approved, 54 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
AlteplaseApproved (phase 4)
ApixabanApproved (phase 4)
AspirinApproved (phase 4)
AtenololApproved (phase 4)
Candesartan CilexetilApproved (phase 4)
CelecoxibApproved (phase 4)
DipyridamoleApproved (phase 4)
EplerenoneApproved (phase 4)
EvolocumabApproved (phase 4)
NadololApproved (phase 4)
Olmesartan MedoxomilApproved (phase 4)
RamiprilApproved (phase 4)
RivaroxabanApproved (phase 4)
SimvastatinApproved (phase 4)
TelmisartanApproved (phase 4)
TicagrelorApproved (phase 4)
TorsemideApproved (phase 4)
ValsartanApproved (phase 4)
AbciximabPhase 3 (in late-stage trials)
CitalopramPhase 3 (in late-stage trials)
CiticolinePhase 3 (in late-stage trials)
ClevidipinePhase 3 (in late-stage trials)
ClopidogrelPhase 3 (in late-stage trials)
CromolynPhase 3 (in late-stage trials)
DabigatranPhase 3 (in late-stage trials)
Dabigatran EtexilatePhase 3 (in late-stage trials)
DalfampridinePhase 3 (in late-stage trials)
Dalteparin SodiumPhase 3 (in late-stage trials)
DesmoteplasePhase 3 (in late-stage trials)
DexborneolPhase 3 (in late-stage trials)
DonepezilPhase 3 (in late-stage trials)
EdoxabanPhase 3 (in late-stage trials)
EpinephrinePhase 3 (in late-stage trials)
Estrogens, ConjugatedPhase 3 (in late-stage trials)
EtomidatePhase 3 (in late-stage trials)
FluoxetinePhase 3 (in late-stage trials)
FospropofolPhase 3 (in late-stage trials)
HeparinPhase 3 (in late-stage trials)
HydroxyureaPhase 3 (in late-stage trials)
ImatinibPhase 3 (in late-stage trials)
IncobotulinumtoxinaPhase 3 (in late-stage trials)
InosinePhase 3 (in late-stage trials)
LevodopaPhase 3 (in late-stage trials)
LidocainePhase 3 (in late-stage trials)
Lipoic Acid, AlphaPhase 3 (in late-stage trials)
Lithium CarbonatePhase 3 (in late-stage trials)
Magnesium Sulfate AnhydrousPhase 3 (in late-stage trials)
MelatoninPhase 3 (in late-stage trials)
MethylprednisolonePhase 3 (in late-stage trials)
ModafinilPhase 3 (in late-stage trials)
NerinetidePhase 3 (in late-stage trials)
NiacinPhase 3 (in late-stage trials)
NiacinamidePhase 3 (in late-stage trials)
NitroglycerinPhase 3 (in late-stage trials)
NorepinephrinePhase 3 (in late-stage trials)
OnabotulinumtoxinaPhase 3 (in late-stage trials)
PhenylephrinePhase 3 (in late-stage trials)
PlasminogenPhase 3 (in late-stage trials)
PrednisolonePhase 3 (in late-stage trials)
PropofolPhase 3 (in late-stage trials)
RemifentanilPhase 3 (in late-stage trials)
RiboflavinPhase 3 (in late-stage trials)
RosuvastatinPhase 3 (in late-stage trials)
Salicylic AcidPhase 3 (in late-stage trials)
Sodium ChloridePhase 3 (in late-stage trials)
SovatelitidePhase 3 (in late-stage trials)
Succinic AcidPhase 3 (in late-stage trials)
SuxamethoniumPhase 3 (in late-stage trials)
TenecteplasePhase 3 (in late-stage trials)
UrapidilPhase 3 (in late-stage trials)
UrokinasePhase 3 (in late-stage trials)
WarfarinPhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acetazolamide, Acetylcysteine, Amantadine, Armodafinil, Atorvastatin, Cilostazol, Cycloserine, Dapsone, Deferiprone, Dextroamphetamine, Drotrecogin Alfa (Activated), Edaravone, Enalapril, Enoxaparin Sodium, Epoetin Alfa, Eptifibatide, Escitalopram, Exenatide, Filgrastim, Fingolimod, Ghrelin, Glyburide, Guanfacine, Hydralazine, Insulin Human, Isosorbide Mononitrate, Labetalol, Levosimendan, Mannitol, Maraviroc, Minocycline, Nebivolol, Nicardipine, Nimodipine, Nitric Oxide, Ocriplasmin, Olmesartan, Oxygen, Pioglitazone, Platelets, Primidone, Propranolol, Reteplase, Ropinirole, Rotigotine, Sodium Acetate, Tadalafil, Tirofiban.

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 5 · Phased (≥1): 7 · Undrugged: 68

Druggability breadth: 47 of 139 evidence-associated genes (34%) 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
RUNX1APOMORPHINE HYDROCHLORIDE
SLC22A3PROGESTERONE
HDAC9CELECOXIB
MARS2CHLORAMPHENICOL

Top cohort targets by molecule count

SymbolMoleculesMax phase
HDAC9284
SLC22A3204
RUNX124
SMARCA422
SORT113
PARK712
MARS214
SEMA3A00
SLC7A700
SPARC00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
APOMORPHINE HYDROCHLORIDE4RUNX1
PROGESTERONE4SLC22A3
COLCHICINE4SLC22A3
IMIPRAMINE4SLC22A3
CLONIDINE4SLC22A3
ESTRADIOL4SLC22A3
IBRUTINIB4SLC22A3
PRAZOSIN4SLC22A3
NILOTINIB4SLC22A3
BITHIONOL4SLC22A3
ONDANSETRON4SLC22A3
IRINOTECAN4SLC22A3
PENTAMIDINE4SLC22A3
MITOXANTRONE4SLC22A3
DESIPRAMINE4SLC22A3
PHENOXYBENZAMINE4SLC22A3
CHLORHEXIDINE4SLC22A3
FAMOTIDINE4SLC22A3
IMATINIB4SLC22A3
CELECOXIB4HDAC9
PHENYLBUTANOIC ACID4HDAC9
SODIUM PHENYLBUTYRATE4HDAC9
ROMIDEPSIN4HDAC9
BELINOSTAT4HDAC9
PANOBINOSTAT4HDAC9
VORINOSTAT4HDAC9
GIVINOSTAT4HDAC9
CHLORAMPHENICOL4MARS2
CORTICOSTERONE3SLC22A3
REMINERTANT3SORT1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

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

SymbolAssaysType breakdown
HDAC91,625Binding:1612, ADMET:8, Functional:4, Toxicity:1
SMARCA4230Binding:207, ADMET:12, Functional:11
WNK1165Binding:165
PARK762Binding:62
SLC22A333Binding:17, Functional:11, ADMET:5
ALDH1A232Binding:32
KCNG321Binding:20, Toxicity:1
RUNX120Binding:17, Functional:3
SORT117Binding:15, ADMET:2
ADAMTS76Binding:6
WDR125Binding:5
UVRAG2Binding:2
ZBTB142Binding:2
ADGRL42Binding:2
HNF1A1Binding:1
TGFBI1Binding:1
RNF2131Binding:1
ADAMTS121Binding:1
CDC5L1Binding:1
CHD31Binding:1
MARS21ADMET:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
UVRAG2.7.1.137phosphatidylinositol 3-kinase
HDAC93.5.1.98histone deacetylase
ALDH1A21.2.1.36retinal dehydrogenase
PARK73.5.1.124, 4.2.1.130protein deglycase, D-lactate dehydratase
REM23.4.23.15renin
ADAMTS23.4.24.14procollagen N-endopeptidase

Cohort genes with high screening signal

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

SymbolChEMBL assays
SMARCA4230
HDAC91,625
WNK1165

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

29 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)
APOMORPHINE HYDROCHLORIDE4RUNX1
PROGESTERONE4SLC22A3
IMIPRAMINE4SLC22A3
CLONIDINE4SLC22A3
ESTRADIOL4SLC22A3
IBRUTINIB4SLC22A3
PRAZOSIN4SLC22A3
NILOTINIB4SLC22A3
BITHIONOL4SLC22A3
ONDANSETRON4SLC22A3
IRINOTECAN4SLC22A3
PENTAMIDINE4SLC22A3
MITOXANTRONE4SLC22A3
DESIPRAMINE4SLC22A3
PHENOXYBENZAMINE4SLC22A3
CHLORHEXIDINE4SLC22A3
FAMOTIDINE4SLC22A3
IMATINIB4SLC22A3
CELECOXIB4HDAC9
PHENYLBUTANOIC ACID4HDAC9
SODIUM PHENYLBUTYRATE4HDAC9
ROMIDEPSIN4HDAC9
BELINOSTAT4HDAC9
PANOBINOSTAT4HDAC9
VORINOSTAT4HDAC9
GIVINOSTAT4HDAC9
CHLORAMPHENICOL4MARS2
CORTICOSTERONE3SLC22A3
REMINERTANT3SORT1

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)4RUNX1, SLC22A3, HDAC9, MARS2
BPhased (≥1) drug, not yet approved3SMARCA4, SORT1, PARK7
CDruggable family + PDB, no drug8SLC7A7, UVRAG, WNK1, ALDH1A2, ULK4, ERRFI1, REM2, ADGRL4
DDruggable family + AlphaFold only, no drug6SEMA3A, ADAMTS12, KCNG3, LPAL2, ADAMTS2, ADAMTS7
EDifficult family or no structure, no drug54SPARC, SPI1, SPINK2, SUPT3H, HNF1A, TCF21, TGFBI, UQCRFS1, XK, ZBTB14 (+44 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
WNK1165—
SEMA3A0—
SLC7A70—
SPARC0—
SPI10—
SPINK20—
SUPT3H0—
HNF1A1—
TCF210—
TGFBI1—
UQCRFS10—
UVRAG2—
XK0—
ZBTB142—
ZNF1600—
WDR125—
ICA1L0—
RNF2131—
LRP100—
ADAMTS121—
NIN0—
WFDC10—
ALDH1A232—
IL1F100—
IL36RN0—
ULK40—
RASD10—
ABCC130—
SFXN40—
DAPP10—

Clinical trials & evidence

Clinical trials

Clinical trials: 5,951.

Phase distribution (across all retrieved trials)

PhaseTrials
PHASE2246
PHASE3194
Not specified193
PHASE4155
PHASE1130
PHASE1/PHASE282
EARLY_PHASE151
PHASE2/PHASE349

Top trials by phase / activity

NCTPhaseStatusTitle
NCT02670161PHASE4ENROLLING_BY_INVITATIONQuality Improvement and Practice Based Research in Neurology Using the EMR
NCT03568890PHASE4ACTIVE_NOT_RECRUITINGShort-Term Anticoagulation Versus Antiplatelet Therapy for Preventing Device Thrombosis Following Left Atrial Appendage Closure
NCT03862859PHASE4RECRUITINGThe Danish Warfarin-Dialysis Study - Safety and Efficacy of Warfarin in Patients With Atrial Fibrillation on Dialysis
NCT03968393PHASE4RECRUITINGAnticoagulation for Stroke Prevention In Patients With Recent Episodes of Atrial Fibrillation Occurring Transiently With Stress
NCT04436978PHASE4RECRUITINGWhat is the Optimal Antithrombotic Strategy in Patients With Atrial Fibrillation Undergoing PCI?
NCT04908423PHASE4RECRUITINGXeomin® and Gait Related Mobility After Stroke
NCT05169021PHASE4NOT_YET_RECRUITINGFolic Acid and Intensive Antihypertensive Therapy for Hypertension With CSVD
NCT05260125PHASE4RECRUITINGComparison of the Efficacy of Ultrasound Guided vs Non-guided Suprascapular Nerve Block Treatment in Stroke Patients
NCT05284747PHASE4ACTIVE_NOT_RECRUITINGEVOLVE-MI: EVOLocumab Very Early After Myocardial Infarction
NCT06108414PHASE4RECRUITINGLow-dose Versus Standard-dose Rivaroxaban in Elderly Patients With Atrial Fibrillation
NCT06429332PHASE4RECRUITINGInternational Care Bundle Evaluation in Cerebral Hemorrhage Research
NCT06486792PHASE4NOT_YET_RECRUITINGStroke Prevention In Ischemic Stroke With Covert Atrial Fibrillation
NCT06526117PHASE4RECRUITINGStroke Prevention in Nigeria 2 Trial
NCT06543758PHASE4RECRUITINGEffectiveness and Safety of At-home Gait Rehabilitation Using Wearable Exoskeletal Robot
NCT06823999PHASE4NOT_YET_RECRUITINGPrevention and Treatment for Bruises in Patients With Ischemic Stroke
NCT06897176PHASE4RECRUITINGEffects of Cerebrolysin on Language Ability in Non-fluent Aphasia Patients After Stroke: A Randomized, Placebo-controlled, Double-blinded, Single Center Study
NCT06899464PHASE4NOT_YET_RECRUITINGSafety and Feasibility of Using Cerebrolysin in the Treatment of Primary Intracerebral Hemorrhage - a Prospective Randomized Open Blinded End-point Trial
NCT06921616PHASE4NOT_YET_RECRUITINGNeuroendoscopic Hematoma Evacuation Combined With Methylprednisolone Sodium Succinate in the Treatment of Lobar Intracerebral Hemorrhage at the Early Stage.
NCT06924983PHASE4NOT_YET_RECRUITINGNeuroendoscopic Hematoma Evacuation Combined With Methylprednisolone Sodium Succinate in the Treatment of Basal Ganglia Intracerebral Hemorrhage at the Early Stage
NCT07095790PHASE4RECRUITINGTirofiban With Sequential Dual Antiplatelet Therapy in Mild Stroke
NCT07111559PHASE4RECRUITINGLacunar Stroke hyperAcute Clinical Utilization of Novel Approach Regimens: Rt-PA vs. DAPT Randomised Clinical Trial
NCT07237308PHASE4NOT_YET_RECRUITINGBEACON-AA: Apixaban With or Without Clopidogrel in Stroke Patients With Atrial Fibrillation and Cerebral Atherosclerosis
NCT07519044PHASE4RECRUITINGSafety and Efficacy of Adjunctive GM1 to Mechanical Thrombectomy for Acute Anterior Circulation Large Vessel Occlusion
NCT00004727PHASE4COMPLETEDAntiplatelet Therapy to Prevent Stroke in African Americans
NCT00029172PHASE4COMPLETEDTreatment for Post-Stroke Depression
NCT00079638PHASE4COMPLETEDComparative Efficacy Evaluation of Lipids When Treated With Niaspan & Statin or Other Lipid-Modifying Therapies-COMPELL
NCT00101543PHASE4COMPLETEDGait Training For Acute Stroke: Functional Neuromuscular Stimulation (FNS) and Weight Supported Treadmill Training
NCT00102869PHASE4COMPLETEDDopaminergic Enhancement of Learning and Memory in Aphasia
NCT00106886PHASE4UNKNOWNHOPE-2 Study (Heart Outcomes Prevention Evaluation-2 Study)
NCT00108706PHASE4UNKNOWNAcute Candesartan Cilexetil Outcomes Stroke Trial (ACCOST)
NCT00126087PHASE4TERMINATEDPotentiation of Procedural Motor Learning in Health and Disease
NCT00149227PHASE4COMPLETEDAdd-on Effects of Valsartan on Morbi- Mortality (KYOTO HEART Study)
NCT00153062PHASE4COMPLETEDPRoFESS - Prevention Regimen For Effectively Avoiding Second Strokes
NCT00153946PHASE4COMPLETEDEdaravone and Argatroban Stroke Therapy Study for Acute Ischemic Stroke
NCT00163150PHASE4COMPLETEDVasomotor Reactivity In Cerebral Small Vessel Disease And New Approach To Treat Lacunar Stroke
NCT00177424PHASE4TERMINATEDSertraline for Preventing Post-stroke Depression and Improving Rehabilitation Outcomes
NCT00178646PHASE4COMPLETEDComparative Efficacy of Three Preparations of Botox-A in Treating Spasticity
NCT00196690PHASE4COMPLETEDDonepezil in Chronic Poststroke Aphasia: a Randomized Controlled Trial
NCT00196703PHASE4UNKNOWNMemantine and Constraint-Induced Language Therapy in Chronic Poststroke Aphasia:A Randomized Controlled Trial
NCT00216411PHASE4COMPLETEDEffects on Quality of Life Following Dysport Treatment in Post-stroke Spasticity of the Arm

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
ASPIRIN440
ALTEPLASE417
TENECTEPLASE411
WARFARIN411
BOTULINUM TOXIN TYPE A49
CARBIDOPA ANHYDROUS49
CLOPIDOGREL49
APIXABAN48
RIVAROXABAN48
ATORVASTATIN47
CILOSTAZOL46
FINGOLIMOD46
ROSUVASTATIN46
DABIGATRAN ETEXILATE45
ABCIXIMAB44
EDOXABAN44
HYDROXYUREA44
LOSARTAN44
ONABOTULINUMTOXINA44
COLCHICINE43
DONEPEZIL43
EDARAVONE43
EPTIFIBATIDE43
LEVODOPA43
MANNITOL43
MARAVIROC43
MINOCYCLINE43
NICARDIPINE43
SORBITOL43
ACENOCOUMAROL42

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 72

This page pulls from 72 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptuberonufeatureumlsuniprot