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Atlas / Disease / Large artery stroke

Large artery stroke

disease
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Summary

Large artery stroke (MONDO:0005490) is a disease with 41 cohort genes (122 GWAS associations across 27 studies).

At a glance

  • Cohort genes: 41
  • GWAS associations: 122

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namelarge artery stroke
Mondo IDMONDO:0005490
EFOEFO:0005524
Is cancer (heuristic)no

Data availability: 122 GWAS associations (27 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › arterial disorder › large artery stroke

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, hypotensive disorder, 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

Genetics & variants

GWAS landscape

122 GWAS associations across 27 studies. Top hits map to 37 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs13330491e-59CDKN2B-AS1C
rs557304997e-43LPAT1.27
rs21075955e-17HDAC9 - TWIST1A1.1
rs5998398e-17CELSR2 - PSRC1?
rs5324364e-15ABOA1.09
rs14124444e-15LIPAT1.07
rs104558729e-14LPA?
rs111721134e-13LRP1?0.02
rs715242632e-12HDAC9?7.05
rs24879287e-12JCADA1.06
rs107746258e-12ATXN2A1.06
rs176127421e-11EDNRA?
rs11226082e-11SMARCA4?
rs47149552e-11PHACTR1?
rs129365872e-10PEMT - SMCR2?
rs110659873e-10ATXN2-AS?
rs115569248e-10UBE2H-DT, ZC3HC1?
rs9641849e-10ZPR1?
rs768663869e-10ABCG8T1.11
rs121223411e-09LINC01765G1.19
rs18784061e-09PRMT5P1 - EDNRAT1.08
rs127929122e-09RNU7-159P - MMP13T1.05
rs80274502e-09FURINT1.06
rs7484313e-09FGD5G1.05
rs1814016794e-09ATP6V1G1P7 - RPL7P45G152128576
rs119840415e-09HDAC9T1.24
rs108402935e-09SWAP70A1.05
rs66476e-09SERPINA1G1.22
rs121245336e-09LINC01765?1.16
rs1383640697e-09FAF1T3.57

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90104542Mishra A20226,3991,234,808Stroke genetics informs drug discovery and risk prediction across ancestries.
GCST90162544Mishra A20226,3991,234,808Stroke genetics informs drug discovery and risk prediction across ancestries.
GCST90162545Mishra A20225,532237,242Stroke genetics informs drug discovery and risk prediction across ancestries.
GCST90103796Daghals I20224,373613,368Migraine, Stroke, and Cervical Arterial Dissection: Shared Genetics for a Triad of Brain Disorders With Vascular Involvement.
GCST005840Malik R20184,373297,290Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.
GCST006907Malik R20184,373297,290Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.
GCST010158von Berg J20203,49528,026Alternate approach to stroke phenotyping identifies a genetic risk locus for small vessel stroke.
GCST010161von Berg J20202,44928,026Alternate approach to stroke phenotyping identifies a genetic risk locus for small vessel stroke.
GCST003259Pulit SL20152,34926,690Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study.
GCST010160von Berg J20202,31828,026Alternate approach to stroke phenotyping identifies a genetic risk locus for small vessel stroke.

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)49
low_freq (0.01-0.05)0
rare (<0.01)0
unknown1

Functional consequences

ConsequenceCount
intron_variant30
intergenic_variant11
non_coding_transcript_exon_variant3
regulatory_region_variant2
missense_variant2
3_prime_UTR_variant2

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs1333049922125504G>A,C0.05intergenic_variantCDKN2B-AS11e-59Tier 4: intronic/intergenic
rs557304996160584578C>T0.065intron_variantLPA7e-43Tier 4: intronic/intergenic
rs2107595719009765G>A,C,T0.168regulatory_region_variantHDAC9 - TWIST15e-17Tier 3: regulatory
rs5998391109279544G>A,C,T0.05intergenic_variantCELSR2 - PSRC18e-17Tier 4: intronic/intergenic
rs5324369133274414A>G,T0.194intron_variantABO4e-15Tier 4: intronic/intergenic
rs14124441089243170C>A,G,T0.332intron_variantLIPA4e-15Tier 4: intronic/intergenic
rs104558726160589086A>G0.05intron_variantLPA9e-14Tier 4: intronic/intergenic
rs111721131257133500T>C,G0.05intron_variantLRP14e-13Tier 4: intronic/intergenic
rs71524263718990655C>A,G,T0.05intron_variantHDAC92e-12Tier 4: intronic/intergenic
rs24879281030034963G>A0.451intron_variantJCAD7e-12Tier 4: intronic/intergenic
rs1077462512111472415A>C,G,T0.489intron_variantATXN28e-12Tier 4: intronic/intergenic
rs176127424147493499T>C0.05non_coding_transcript_exon_variantEDNRA1e-11Tier 4: intronic/intergenic
rs11226081911052925G>T0.05intron_variantSMARCA42e-11Tier 4: intronic/intergenic
rs4714955612903203C>A,T0.05intron_variantPHACTR12e-11Tier 4: intronic/intergenic
rs129365871717640408G>A0.05intergenic_variantPEMT - SMCR22e-10Tier 4: intronic/intergenic
rs1106598712111634620A>G0.05intron_variantATXN2-AS3e-10Tier 4: intronic/intergenic
rs115569247130023656C>A,T0.05missense_variantUBE2H-DT, ZC3HC18e-10Tier 1: coding
rs96418411116778201G>C0.053_prime_UTR_variantZPR19e-10Tier 2: splice/UTR
rs76866386243848344T>C0.064intron_variantABCG89e-10Tier 4: intronic/intergenic
rs121223411115113069C>G0.257intron_variantLINC017651e-09Tier 4: intronic/intergenic
rs18784064147472512C>A,G,T0.142intergenic_variantPRMT5P1 - EDNRA1e-09Tier 4: intronic/intergenic
rs1279291211102930574T>A,G0.43intergenic_variantRNU7-159P - MMP132e-09Tier 4: intronic/intergenic
rs80274501590875164C>A,T0.326intron_variantFURIN2e-09Tier 4: intronic/intergenic
rs748431314886570G>C,T0.379intron_variantFGD53e-09Tier 4: intronic/intergenic
rs18140167913104244508C>Gintergenic_variantATP6V1G1P7 - RPL7P454e-09Tier 4: intronic/intergenic
rs11984041718992312C>T0.093intron_variantHDAC95e-09Tier 4: intronic/intergenic
rs10840293119729649G>A,C0.423intron_variantSWAP705e-09Tier 4: intronic/intergenic
rs66471494381078A>C,G0.18missense_variantSERPINA16e-09Tier 1: coding
rs121245331115115178C>T0.05intron_variantLINC017656e-09Tier 4: intronic/intergenic
rs138364069150832533C>T0.05intron_variantFAF17e-09Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 25 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
CNNM2Orphanet:620363Primary hypomagnesemia-generalized seizures-intellectual disability-obesity syndrome
SLCO1B1Orphanet:3111Rotor syndrome
SMARCA4Orphanet:1465Coffin-Siris syndrome
SMARCA4Orphanet:231108Rhabdoid tumor predisposition syndrome
SMARCA4Orphanet:370396Small cell carcinoma of the ovary
SMARCA4Orphanet:466962SMARCA4-deficient sarcoma of thorax
TWIST1Orphanet:35093Non-syndromic sagittal craniosynostosis
TWIST1Orphanet:35099Non-syndromic bicoronal craniosynostosis
TWIST1Orphanet:794Saethre-Chotzen syndrome
CARD9Orphanet:457088Predisposition to invasive fungal disease due to CARD9 deficiency
TTLL5Orphanet:1872Cone rod dystrophy
PHACTR1Orphanet:697160Infantile epileptic spasms syndrome
ALKBH8Orphanet:88616Autosomal recessive non-syndromic intellectual disability
SH2B3Orphanet:3318Essential thrombocythemia
SH2B3Orphanet:391366Growth retardation-mild developmental delay-chronic hepatitis syndrome
EDNRAOrphanet:443995Mandibulofacial dysostosis with alopecia
EDNRAOrphanet:586Cystic fibrosis
LDLROrphanet:391665Homozygous familial hypercholesterolemia
NT5C2Orphanet:320396Autosomal recessive spastic paraplegia type 45
SERPINA1Orphanet:178396Hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation
SERPINA1Orphanet:586Cystic fibrosis
SERPINA1Orphanet:60Alpha-1-antitrypsin deficiency
RAI1Orphanet:171317p11.2 microduplication syndrome
RAI1Orphanet:477817PMP22-RAI1 contiguous gene duplication syndrome
RAI1Orphanet:819Smith-Magenis syndrome

Cohort genes → proteins

41 cohort genes, 39 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only41

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
CNNM2HGNC:103ENSG00000148842Q9H8M5Metal transporter CNNM2gwas
SLCO1B1HGNC:10959ENSG00000134538Q9Y6L6Solute carrier organic anion transporter family member 1B1gwas
SLC22A3HGNC:10967ENSG00000146477O75751Solute carrier family 22 member 3gwas
SMARCA4HGNC:11100ENSG00000127616P51532SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4gwas
SORT1HGNC:11186ENSG00000134243Q99523Sortilingwas
SUPT3HHGNC:11466ENSG00000196284O75486Transcription initiation protein SPT3 homologgwas
TCF21HGNC:11632ENSG00000118526O43680Transcription factor 21gwas
TWIST1HGNC:12428ENSG00000122691Q15672Twist-related protein 1gwas
ZPR1HGNC:13051ENSG00000109917O75312Zinc finger protein ZPR1gwas
HDAC9HGNC:14065ENSG00000048052Q9UKV0Histone deacetylase 9gwas
WDR12HGNC:14098ENSG00000138442Q9GZL7Ribosome biogenesis protein WDR12gwas
RASD1HGNC:15828ENSG00000108551Q9Y272Dexamethasone-induced Ras-related protein 1gwas
CARD9HGNC:16391ENSG00000187796Q9H257Caspase recruitment domain-containing protein 9gwas
CDKN2CHGNC:1789ENSG00000123080P42773Cyclin-dependent kinase 4 inhibitor Cgwas
TTLL5HGNC:19963ENSG00000119685Q6EMB2Tubulin polyglutamylase TTLL5gwas
ZDHHC22HGNC:20106ENSG00000177108Q8N966Palmitoyltransferase ZDHHC22gwas
OBI1HGNC:20308ENSG00000152193Q5W0B1ORC ubiquitin ligase 1gwas
TSPAN2HGNC:20659ENSG00000134198O60636Tetraspanin-2gwas
PHACTR1HGNC:20990ENSG00000112137Q9C0D0Phosphatase and actin regulator 1gwas
LPAL2HGNC:21210ENSG00000213071Q16609Putative apolipoprotein(a)-like protein 2gwas
ADAMTS7HGNC:223ENSG00000136378Q9UKP4A disintegrin and metalloproteinase with thrombospondin motifs 7gwas
ALKBH8HGNC:25189ENSG00000137760Q96BT7tRNA (carboxymethyluridine(34)-5-O)-methyltransferase ALKBH8gwas
TMEM163HGNC:25380ENSG00000152128Q8TC26Transmembrane protein 163gwas
SH3YL1HGNC:29546ENSG00000035115Q96HL8SH3 domain-containing YSC84-like protein 1gwas
SH2B3HGNC:29605ENSG00000111252Q9UQQ2SH2B adapter protein 3gwas
ZC3HC1HGNC:29913ENSG00000091732Q86WB0Zinc finger C3HC-type protein 1gwas
DTLHGNC:30288ENSG00000143476Q9NZJ0Denticleless protein homologgwas
EDNRAHGNC:3179ENSG00000151617P25101Endothelin-1 receptorgwas
CDKN2B-AS1HGNC:34341ENSG00000240498CDKN2B and CDKN2A antisense cis and trans regulatory RNA 1gwas
FAF1HGNC:3578ENSG00000185104Q9UNN5FAS-associated factor 1gwas
MCHR1HGNC:4479ENSG00000128285Q99705Melanin-concentrating hormone receptor 1gwas
LINC01492HGNC:51149ENSG00000225564long intergenic non-protein coding RNA 1492gwas
LDLRHGNC:6547ENSG00000130164P01130Low-density lipoprotein receptorgwas
LPAHGNC:6667ENSG00000198670P08519Apolipoprotein(a)gwas
NDUFAB1HGNC:7694ENSG00000004779O14561Acyl carrier protein, mitochondrialgwas
ABOHGNC:79ENSG00000175164P16442Histo-blood group ABO system transferasegwas
NT5C2HGNC:8022ENSG00000076685P49902Cytosolic purine 5’-nucleotidasegwas
PEMTHGNC:8830ENSG00000133027Q9UBM1Phosphatidylethanolamine N-methyltransferasegwas
SERPINA1HGNC:8941ENSG00000197249P01009Alpha-1-antitrypsingwas
PLPP3HGNC:9229ENSG00000162407O14495Phospholipid phosphatase 3gwas
RAI1HGNC:9834ENSG00000108557Q7Z5J4Retinoic acid-induced protein 1gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
CNNM2Metal transporter CNNM2Divalent metal cation transporter.
SLCO1B1Solute carrier organic anion transporter family member 1B1Mediates the Na(+)-independent uptake of organic anions.
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.
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.
SUPT3HTranscription initiation protein SPT3 homologProbable transcriptional activator.
TCF21Transcription factor 21Involved in epithelial-mesenchymal interactions in kidney and lung morphogenesis that include epithelial differentiation and branching morphogenesis.
TWIST1Twist-related protein 1Acts as a transcriptional regulator.
ZPR1Zinc finger protein ZPR1Acts as a signaling molecule that communicates proliferative growth signals from the cytoplasm to the nucleus.
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.
RASD1Dexamethasone-induced Ras-related protein 1Small GTPase.
CARD9Caspase recruitment domain-containing protein 9Adapter protein that plays a key role in innate immune response against fungi by forming signaling complexes downstream of C-type lectin receptors.
CDKN2CCyclin-dependent kinase 4 inhibitor CInteracts strongly with CDK6, weakly with CDK4.
TTLL5Tubulin polyglutamylase TTLL5Polyglutamylase which modifies tubulin, generating polyglutamate side chains on the gamma-carboxyl group of specific glutamate residues within the C-terminal tail of tubulin.
ZDHHC22Palmitoyltransferase ZDHHC22Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates and be involved in a variety of cellular processes.
OBI1ORC ubiquitin ligase 1E3 ubiquitin ligase essential for DNA replication origin activation during S phase.
TSPAN2Tetraspanin-2May play a role in signalling in oligodendrocytes in the early stages of their terminal differentiation into myelin-forming glia and may also function in stabilizing the mature sheath.
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…
ADAMTS7A disintegrin and metalloproteinase with thrombospondin motifs 7Metalloprotease.
ALKBH8tRNA (carboxymethyluridine(34)-5-O)-methyltransferase ALKBH8Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its methyltransferase domain.
TMEM163Transmembrane protein 163Zinc ion transporter that mediates zinc efflux and plays a crucial role in intracellular zinc homeostasis.
SH2B3SH2B adapter protein 3Links T-cell receptor activation signal to phospholipase C-gamma-1, GRB2 and phosphatidylinositol 3-kinase.
ZC3HC1Zinc finger C3HC-type protein 1Required for proper positioning of a substantial amount of TPR at the nuclear basket (NB) through interaction with TPR.
DTLDenticleless protein homologSubstrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis.
EDNRAEndothelin-1 receptorReceptor for endothelin-1.
FAF1FAS-associated factor 1Ubiquitin-binding protein.
MCHR1Melanin-concentrating hormone receptor 1Receptor for melanin-concentrating hormone, coupled to both G proteins that inhibit adenylyl cyclase and G proteins that activate phosphoinositide hydrolysis.
LDLRLow-density lipoprotein receptorBinds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis.
LPAApolipoprotein(a)Apo(a) is the main constituent of lipoprotein(a) (Lp(a)).
NDUFAB1Acyl carrier protein, mitochondrialCarrier of the growing fatty acid chain in fatty acid biosynthesis.
ABOHisto-blood group ABO system transferaseThis protein is the basis of the ABO blood group system.
NT5C2Cytosolic purine 5’-nucleotidaseBroad specificity cytosolic 5’-nucleotidase that catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5’-monophosphates.
PEMTPhosphatidylethanolamine N-methyltransferaseCatalyzes the three sequential steps of the methylation pathway for the biosynthesis of phosphatidylcholine, a critical and essential component for membrane structure.
SERPINA1Alpha-1-antitrypsinInhibitor of serine proteases.
PLPP3Phospholipid phosphatase 3Magnesium-independent phospholipid phosphatase of the plasma membrane that catalyzes the dephosphorylation of a variety of glycerolipid and sphingolipid phosphate esters including phosphatidate/PA, lysophosphatidate/LPA, diacylglycerol pyr…
RAI1Retinoic acid-induced protein 1Transcriptional regulator of the circadian clock components: CLOCK, BMAL1, BMAL2, PER1/3, CRY1/2, NR1D1/2 and RORA/C.

Protein-family classification

Druggable: 13 · Difficult: 11 · Unknown: 17 · Druggable fraction: 0.32

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
Scaffold/PPI62.5×0.205
Transporter23.8×0.215
Protease32.7×0.215
Enzyme (other)61.8×0.215
GPCR21.2×0.659
Transcription factor51.0×0.659
Other/Unknown170.7×0.977

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
CNNM2Other/UnknownnoCBS_dom, CNNM, RmlC-like_jellyroll
SLCO1B1TransporteryesKazal_dom, OATP, MFS_dom
SLC22A3TransporteryesOrgcat_transp/SVOP, Sugar_transporter_CS, MFS
SMARCA4Other/UnknownnoSNF2_N, Bromodomain, Helicase_C-like
SORT1Scaffold/PPInoVPS10, WD40/YVTN_repeat-like_dom_sf, Sortilin_C
SUPT3HOther/UnknownnoTFIID_TAF13, Histone-fold
TCF21Transcription factornobHLH_dom, HLH_DNA-bd_sf, E-box_TF_Regulators
TWIST1Transcription factornobHLH_dom, HLH_DNA-bd_sf, TWIST1_bHLH
ZPR1Transcription factornoZnf_ZPR1, ZPR1, ZPR1_A/B_dom
HDAC9Enzyme (other)yes3.5.1.98HDACs, Ureohydrolase_dom_sf, His_deacetylse_dom
WDR12Scaffold/PPInoWD40_rpt, NLE, WD40/YVTN_repeat-like_dom_sf
RASD1Other/UnknownnoSmall_GTPase, Small_GTP-bd, P-loop_NTPase
CARD9Other/UnknownnoCARD, DEATH-like_dom_sf, CARD_CARD9
CDKN2CScaffold/PPInoAnkyrin_rpt, Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor
TTLL5Other/UnknownnoTTL/TTLL_fam
ZDHHC22Other/UnknownnoSSD, Palmitoyltrfase_DHHC, PFA4/ZDH16/20/ERF2-like
OBI1Transcription factornoZnf_RING, Znf_RING/FYVE/PHD, OBI1_RING-HC
TSPAN2Other/UnknownnoTetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin
PHACTR1Other/UnknownnoRPEL_repeat
LPAL2ProteaseyesKringle, Kringle-like, Kringle_CS
ADAMTS7ProteaseyesTSP1_rpt, Peptidase_M12B, Peptidase_M12B_N
ALKBH8Enzyme (other)yes2.1.1.229RRM_dom, Oxoglu/Fe-dep_dioxygenase_dom, Nucleotide-bd_a/b_plait_sf
TMEM163Other/UnknownnoTmem163, Cation_efflux_TMD_sf
SH3YL1Scaffold/PPInoSH3_domain, Ysc84_actin-binding, SYLF_SH3YL1-like
SH2B3Scaffold/PPInoSH2, PH_domain, PH-like_dom_sf
ZC3HC1Other/UnknownnoNuBaID_N, NuBaID_C
DTLScaffold/PPInoWD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
EDNRAGPCRyesGPCR_Rhodpsn, Endthln_rcpt, ETA_rcpt
CDKN2B-AS1Other/Unknownno
FAF1Other/UnknownnoUBX_dom, UAS, Ubiquitin-like_domsf
MCHR1GPCRyesGPCR_Rhodpsn, MCHR1, MCH_rcpt
LINC01492Other/Unknownno
LDLROther/UnknownnoLDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF
LPAProteaseyesKringle, Trypsin_dom, Peptidase_S1A
NDUFAB1Other/UnknownnoACP, Ppantetheine_attach_site, PP-bd_ACP
ABOEnzyme (other)yes2.4.1.37Glyco_trans_6, Nucleotide-diphossugar_trans
NT5C2Enzyme (other)yes3.1.3.5HAD-SF_hydro_IG_5-nucl, Pur_nucleotidase, HAD_sf
PEMTEnzyme (other)yes2.1.1.17Phopholipid_MeTrfase, PEMT/MFAP
SERPINA1Other/UnknownnoSerpin_fam, Serpin_CS, Serpin_dom
PLPP3Enzyme (other)yes3.1.3.4PAP2/HPO, PAP2/HPO_sf, PAP-like
RAI1Transcription factornoZnf_PHD, Znf_RING/FYVE/PHD, EPHD

Expression context

Cohort genes with no expression data: 0.

40 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)41
unknown0

Top tissues across cohort

TissueCohort genes
oocyte7
secondary oocyte5
male germ line stem cell (sensu Vertebrata) in testis5
right lobe of liver5
cortical plate5
liver4
ganglionic eminence3
right testis3
monocyte3
ventricular zone3
left testis3
right adrenal gland2
corpus epididymis2
primordial germ cell in gonad2
leukocyte2
mononuclear cell2
popliteal artery2
lateral nuclear group of thalamus2
parotid gland2
adrenal tissue2

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
CNNM2234ubiquitousmarkersecondary oocyte, oocyte, right adrenal gland
SLCO1B129tissue_specificmarkerright lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
SLC22A3189broadmarkerthoracic aorta, ascending aorta, descending thoracic aorta
SMARCA4295ubiquitousmarkerganglionic eminence, cortical plate, cervix squamous epithelium
SORT1291ubiquitousmarkerinferior vagus X ganglion, corpus epididymis, subthalamic nucleus
SUPT3H206ubiquitousyesprimordial germ cell in gonad, sperm, male germ line stem cell (sensu Vertebrata) in testis
TCF21175broadmarkerprimordial germ cell in gonad, right lung, upper lobe of left lung
TWIST1233ubiquitousmarkerperiodontal ligament, mucosa of paranasal sinus, oocyte
ZPR1267ubiquitousmarkercortical plate, ganglionic eminence, right testis
HDAC9277ubiquitousmarkeroocyte, monocyte, secondary oocyte
WDR12288ubiquitousmarkerventricular zone, ganglionic eminence, cortical plate
RASD1252ubiquitousmarkerpericardium, renal medulla, kidney epithelium
CARD9172broadmarkermonocyte, mononuclear cell, leukocyte
CDKN2C286ubiquitousmarkerventricular zone, popliteal artery, tibial artery
TTLL5288ubiquitousmarkerleft testis, right testis, testis
ZDHHC22106broadmarkerlateral nuclear group of thalamus, prefrontal cortex, primary visual cortex
OBI1274ubiquitousmarkersecondary oocyte, oocyte, male germ line stem cell (sensu Vertebrata) in testis
TSPAN2228broadmarkerbody of uterus, muscle layer of sigmoid colon, popliteal artery
PHACTR1210ubiquitousmarkercortical plate, postcentral gyrus, nucleus accumbens
LPAL2164tissue_specificmarkerright lobe of liver, granulocyte, liver
ADAMTS7151ubiquitousmarkerright atrium auricular region, cardiac atrium, apex of heart
ALKBH8226ubiquitousmarkercalcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis, cortical plate
TMEM163201broadmarkeroocyte, secondary oocyte, lateral nuclear group of thalamus
SH3YL1294ubiquitousmarkernephron tubule, parotid gland, upper leg skin
SH2B3260ubiquitousmarkermonocyte, mononuclear cell, leukocyte
ZC3HC1245ubiquitousmarkertibialis anterior, oocyte, deltoid
DTL196ubiquitousmarkersecondary oocyte, oocyte, trabecular bone tissue
EDNRA253ubiquitousmarkercauda epididymis, seminal vesicle, visceral pleura
CDKN2B-AS1169ubiquitousmarkermucosa of transverse colon, rectum, transverse colon
FAF1280ubiquitousmarkergastrocnemius, muscle of leg, left testis

Protein interactions among cohort

Intra-cohort edges: 15.

Hub genes (top 10 by interactor count)

SymbolInteractor count
SMARCA48,138
NDUFAB15,533
WDR123,702
CARD93,636
SERPINA13,617
TWIST13,507
RASD13,278
HDAC93,047
ZPR12,581
SORT12,514

Intra-cohort edges

ABSources
ADAMTS7PHACTR1string_interaction
ADAMTS7SORT1string_interaction
ADAMTS7ZC3HC1string_interaction
CDKN2CFAF1string_interaction
CNNM2NT5C2string_interaction
CNNM2ZC3HC1string_interaction
EDNRAZC3HC1string_interaction
HDAC9SERPINA1biogrid_interaction
HDAC9SMARCA4string_interaction
PHACTR1SORT1string_interaction
PHACTR1TSPAN2string_interaction
PHACTR1WDR12string_interaction
PHACTR1ZC3HC1string_interaction
SH2B3ZC3HC1string_interaction
WDR12ZC3HC1string_interaction

Structural data

PDB: 25 · AlphaFold-only: 14 · No structure: 2

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
ABOP16442151
SERPINA1P0100946
NT5C2P4990243
NDUFAB1O1456142
LDLRP0113036
SMARCA4P5153231
SORT1Q9952317
FAF1Q9UNN516
LPAP0851916
MCHR1Q9970510
SLCO1B1Q9Y6L69
CARD9Q9H2578
CNNM2Q9H8M57
CDKN2CP427736
PHACTR1Q9C0D06
DTLQ9NZJ05
EDNRAP251015
SUPT3HO754864
SLC22A3O757513
WDR12Q9GZL73
ALKBH8Q96BT73
TWIST1Q156722
HDAC9Q9UKV02
TTLL5Q6EMB21
SH3YL1Q96HL81

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
PEMTQ9UBM193.45
ZDHHC22Q8N96688.21
TSPAN2O6063687.26
PLPP3O1449584.44
LPAL2Q1660982.18
RASD1Q9Y27280.75
ZPR1O7531280.11
TMEM163Q8TC2676.65
ZC3HC1Q86WB069.40
TCF21O4368066.67
ADAMTS7Q9UKP464.26
SH2B3Q9UQQ263.45
OBI1Q5W0B157.65
RAI1Q7Z5J439.62

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 157. Enrichment computed across 41 evidence-associated genes (27 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 27 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Abacavir ADME2105.7×0.017SLC22A3, NT5C2
Drug ADME325.4×0.017SLCO1B1, SLC22A3, NT5C2
Defective SLCO1B1 causes hyperbilirubinemia, Rotor type (HBLRR)1423.0×0.120SLCO1B1
Nuclear events stimulated by ALK signaling in cancer224.2×0.120TWIST1, ZC3HC1
Plasma lipoprotein assembly, remodeling, and clearance216.9×0.193LDLR, LPA
Abacavir metabolism1105.7×0.209NT5C2
Abacavir transmembrane transport184.6×0.209SLC22A3
Chylomicron clearance184.6×0.209LDLR
LDL remodeling170.5×0.209LPA
Metabolism of porphyrins152.9×0.209SLCO1B1
Atorvastatin ADME152.9×0.209SLCO1B1
Nucleotide catabolism147.0×0.209NT5C2
Purine catabolism138.5×0.209NT5C2
Organic anion transport by SLCO transporters138.5×0.209SLCO1B1
Ribavirin ADME138.5×0.209NT5C2
Protein lipoylation138.5×0.209NDUFAB1
Sphingolipid catabolism132.5×0.209PLPP3
Heme degradation130.2×0.209SLCO1B1
SLC-mediated transport of organic cations128.2×0.209SLC22A3
R-HSA-549132128.2×0.209SLC22A3
Negative regulation of FLT3126.4×0.209SH2B3
Formation of the non-canonical BAF (ncBAF) complex124.9×0.209SMARCA4
Formation of the canonical BAF (cBAF) complex123.5×0.209SMARCA4
Formation of the polybromo-BAF (pBAF) complex123.5×0.209SMARCA4
Regulation of KIT signaling122.3×0.209SH2B3
Recycling of bile acids and salts122.3×0.209SLCO1B1
Formation of the embryonic stem cell BAF (esBAF) complex122.3×0.209SMARCA4
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)210.8×0.209SMARCA4, HDAC9
Negative Regulation of CDH1 Gene Transcription28.9×0.209SMARCA4, TWIST1
Chromatin organization26.0×0.209SMARCA4, SUPT3H

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 38 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
cardiac neural crest cell migration involved in outflow tract morphogenesis2126.7×0.047TWIST1, EDNRA
obsolete GMP catabolic process to guanine1443.5×0.067NT5C2
DNA endoreduplication1443.5×0.067ZPR1
regulation of striated muscle cell differentiation1443.5×0.067HDAC9
regulation of sphingolipid mediated signaling pathway1443.5×0.067PLPP3
regulation of protein localization to cell leading edge1443.5×0.067EDNRA
pre-mRNA catabolic process1443.5×0.067ZPR1
cell proliferation involved in heart valve development1443.5×0.067TWIST1
positive regulation of endocardial cushion to mesenchymal transition involved in heart valve formation1443.5×0.067TWIST1
regulation of phosphatidylcholine catabolic process1221.7×0.067LDLR
regulation of interleukin-2 production1221.7×0.067CARD9
cellular response to human chorionic gonadotropin stimulus1221.7×0.067EDNRA
gland development1221.7×0.067TCF21
epinephrine uptake1221.7×0.067SLC22A3
embryonic camera-type eye formation1221.7×0.067TWIST1
receptor-mediated endocytosis involved in cholesterol transport1221.7×0.067LDLR
zinc ion import into synaptic vesicle1221.7×0.067TMEM163
negative regulation of Kit signaling pathway1221.7×0.067SH2B3
podocyte apoptotic process1221.7×0.067EDNRA
cardiac chamber formation1147.8×0.067EDNRA
branchiomeric skeletal muscle development1147.8×0.067TCF21
monocyte homeostasis1147.8×0.067SH2B3
Fas signaling pathway1147.8×0.067FAF1
GMP metabolic process1147.8×0.067NT5C2
dGMP metabolic process1147.8×0.067NT5C2
regulation of skeletal muscle fiber development1147.8×0.067HDAC9
histamine transport1147.8×0.067SLC22A3
negative regulation of astrocyte activation1147.8×0.067LDLR
metanephric glomerular capillary formation1147.8×0.067TCF21
purine-containing compound transmembrane transport1147.8×0.067SLC22A3

Therapeutics

Drug target analysis

Approved (phase 4): 5 · Phase ≥3: 6 · Phased (≥1): 7 · Undrugged: 34

Druggability breadth: 14 of 41 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
SLCO1B1CANDESARTAN CILEXETIL
SLC22A3PROGESTERONE
HDAC9CELECOXIB
EDNRAAMBRISENTAN
LDLRNILOTINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
SLCO1B1574
EDNRA314
HDAC9284
SLC22A3204
SMARCA422
SORT113
LDLR14
CNNM200
SUPT3H00
TCF2100

Drugs targeting cohort genes (top 30)

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

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

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

SymbolAssaysType breakdown
HDAC91,625Binding:1612, ADMET:8, Functional:4, Toxicity:1
EDNRA418Binding:342, Functional:73, Toxicity:2, ADMET:1
MCHR1267Binding:158, Functional:109
SLCO1B1242Functional:106, ADMET:82, Binding:53, Toxicity:1
SMARCA4230Binding:207, ADMET:12, Functional:11
LDLR55Binding:54, Functional:1
SLC22A333Binding:17, Functional:11, ADMET:5
SORT117Binding:15, ADMET:2
NT5C27Binding:7
ADAMTS76Binding:6
ZC3HC16Binding:6
ABO6Binding:6
WDR125Binding:5
NDUFAB15Binding:5
FAF12Binding:2

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
HDAC93.5.1.98histone deacetylase
ALKBH82.1.1.229tRNA (carboxymethyluridine34-5-O)-methyltransferase
ABO2.4.1.37, 2.4.1.40, 2.4.1.88fucosylgalactoside 3-alpha-galactosyltransferase, glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase, globoside alpha-N-acetylgalactosaminyltransferase
NT5C23.1.3.55’-nucleotidase
PEMT2.1.1.17phosphatidylethanolamine N-methyltransferase
PLPP33.1.3.4phosphatidate phosphatase

Cohort genes with high screening signal

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

SymbolChEMBL assays
SLCO1B1242
SMARCA4230
HDAC91,625
EDNRA418
MCHR1267

Pharmacogenomics

Cohort genes with a PharmGKB record: 40; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

SymbolCPIC guidelines
SLCO1B11

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

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

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)5SLCO1B1, SLC22A3, HDAC9, EDNRA, LDLR
BPhased (≥1) drug, not yet approved2SMARCA4, SORT1
CDruggable family + PDB, no drug5ALKBH8, MCHR1, LPA, ABO, NT5C2
DDruggable family + AlphaFold only, no drug4LPAL2, ADAMTS7, PEMT, PLPP3
EDifficult family or no structure, no drug25CNNM2, SUPT3H, TCF21, TWIST1, ZPR1, WDR12, RASD1, CARD9, CDKN2C, TTLL5 (+15 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
MCHR1267—
CNNM20—
SUPT3H0—
TCF210—
TWIST10—
ZPR10—
WDR125—
RASD10—
CARD90—
CDKN2C0—
TTLL50—
ZDHHC220—
OBI10—
TSPAN20—
PHACTR10—
LPAL20—
ADAMTS76—
ALKBH80—
TMEM1630—
SH3YL10—
SH2B30—
ZC3HC16—
DTL0—
CDKN2B-AS10—
FAF12—
LINC014920—
LPA0—
NDUFAB15—
ABO6—
NT5C27—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

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
v1.1.4
BioBTree
v2.0.2

Sources 66

This page pulls from 66 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureuniprot