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Cocaine dependence

disease
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Also known as cocaine addiction

Summary

Cocaine dependence (MONDO:0005186) is a disease with 38 cohort genes (42 GWAS associations across 5 studies) and 210 clinical trials. Top therapeutic interventions include cocaine, doxazosin, and citalopram.

At a glance

  • Cohort genes: 38
  • GWAS associations: 42
  • Clinical trials: 210

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namecocaine dependence
Mondo IDMONDO:0005186
EFOEFO:0002610
DOIDDOID:9975
ICD-10-CMF14.2
ICD-111691013484
NCITC34492
SNOMED CT31956009
UMLSC0600427
MedGen154705
Is cancer (heuristic)no

Also known as: cocaine addiction

Data availability: 42 GWAS associations (5 studies).

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › substance-related disorder › substance dependence › drug dependence › cocaine dependence

Related subtypes (9): barbiturate dependence, hallucinogen dependence, methamphetamine dependence, alcohol and nicotine codependence, opiate dependence, cannabis dependence, phencyclidine abuse, alcohol dependence, nicotine dependence

Genetics & variants

GWAS landscape

42 GWAS associations across 5 studies. Top hits map to 17 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs618350884e-09FAM78BT0.87
rs28252953e-08PPIAP22 - SLC6A6P1T1.14
rs26295404e-08FAM53B?
rs734047862e-07LINC02932A1.38
rs744263413e-07LINC02932C1.37
rs1113250024e-07MTHFD2P1 - HNRNPKP4?
rs20052904e-07OR3A2?
rs737211034e-07AASS - RPL31P37T1.3
rs1509544315e-07NCOR2?
rs1128947475e-07FGF18 - SMIM23C1.41
rs119443322e-06HAND2-AS1?
rs715754412e-06EFNA5T0.66
rs726854142e-06THAP3P1 - CDK4P1A0.38
rs76755572e-06RASGEF1B - HNRNPA3P13A0.22
rs793094732e-06SPART - CCNA1T0.23
rs41295663e-06HAND2-AS1?
rs728409363e-06STEAP3-AS1?
rs756861223e-06RIMS2?
rs24567783e-06CDK1?
rs564018013e-06VN1R10P - ZNF204PA0.36
rs110865253e-06LINC01440 - CBLN4C0.2
rs8069733e-06H2AC6 - H1-4A0.2
rs47343874e-06POP1 - NIPAL2A0.21
rs1122529074e-06RBFOX1T0.43
rs14848734e-06SLC14A2A0.47
rs573615435e-06GHSR - TNFSF10A0.2
rs677699116e-06ACTN4P1 - RNU6-119PA0.26
rs739732836e-06LINC01898 - LINC01893A0.56
rs101213667e-06DELEC1 - U2T0.28
rs73327267e-06MIR4500HGA0.56

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST012224Sherva R20213,5540Genome-wide association study of phenotypes measuring progression from first cocaine or opioid use to dependence reveals novel risk genes.
GCST012225Sherva R20213,5540Genome-wide association study of phenotypes measuring progression from first cocaine or opioid use to dependence reveals novel risk genes.
GCST012223Sherva R20212,7120Genome-wide association study of phenotypes measuring progression from first cocaine or opioid use to dependence reveals novel risk genes.
GCST008399Cabana-Dominguez J20192,0854,293Genome-wide association meta-analysis of cocaine dependence: Shared genetics with comorbid conditions.
GCST002142Gelernter J20131,8090Genome-wide association study of cocaine dependence and related traits: FAM53B identified as a risk gene.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding1
Tier 2: splice/UTR3
Tier 3: regulatory0
Tier 4: intronic/intergenic33

MAF distribution

BucketVariants
common (>=0.05)34
low_freq (0.01-0.05)2
rare (<0.01)0
unknown1

Functional consequences

ConsequenceCount
intron_variant20
intergenic_variant13
3_prime_UTR_variant1
splice_region_variant1
splice_polypyrimidine_tract_variant1
missense_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs618350881166069605T>C0.143_prime_UTR_variantFAM78B4e-09Tier 2: splice/UTR
rs28252952119031918G>A,C,T0.05intergenic_variantPPIAP22 - SLC6A6P13e-08Tier 4: intronic/intergenic
rs262954010124737579G>C0.05intron_variantFAM53B4e-08Tier 4: intronic/intergenic
rs73404786791354149G>A,T0.05intron_variantLINC029322e-07Tier 4: intronic/intergenic
rs74426341791349301G>C0.04intron_variantLINC029323e-07Tier 4: intronic/intergenic
rs111325002396134788A>Gintergenic_variantMTHFD2P1 - HNRNPKP44e-07Tier 4: intronic/intergenic
rs2005290173284718C>A,G,T0.05intron_variantOR3A24e-07Tier 4: intronic/intergenic
rs737211037122167872G>T0.05intron_variantAASS - RPL31P374e-07Tier 4: intronic/intergenic
rs15095443112124517777C>T0.05splice_region_variantNCOR25e-07Tier 2: splice/UTR
rs1128947475171467315G>C0.03intron_variantFGF18 - SMIM235e-07Tier 4: intronic/intergenic
rs119443324173633681A>C,G0.05intron_variantHAND2-AS12e-06Tier 4: intronic/intergenic
rs715754415107453116T>C0.05intron_variantEFNA52e-06Tier 4: intronic/intergenic
rs726854141104424250C>A0.05intergenic_variantTHAP3P1 - CDK4P12e-06Tier 4: intronic/intergenic
rs7675557482049663G>A,C0.05intergenic_variantRASGEF1B - HNRNPA3P132e-06Tier 4: intronic/intergenic
rs793094731336398065G>T0.05intergenic_variantSPART - CCNA12e-06Tier 4: intronic/intergenic
rs41295664173626006T>C0.05intron_variantHAND2-AS13e-06Tier 4: intronic/intergenic
rs728409362119266116G>C0.05intron_variantSTEAP3-AS13e-06Tier 4: intronic/intergenic
rs756861228103561561C>A,T0.05intron_variantRIMS23e-06Tier 4: intronic/intergenic
rs24567781060792132A>G,T0.05splice_polypyrimidine_tract_variantCDK13e-06Tier 2: splice/UTR
rs56401801627333733T>A0.05intergenic_variantVN1R10P - ZNF204P3e-06Tier 4: intronic/intergenic
rs110865252055941282G>C0.05intergenic_variantLINC01440 - CBLN43e-06Tier 4: intronic/intergenic
rs806973626148098A>G,T0.05intron_variantH2AC6 - H1-43e-06Tier 4: intronic/intergenic
rs4734387898181537G>A0.05intergenic_variantPOP1 - NIPAL24e-06Tier 4: intronic/intergenic
rs112252907166625140C>G,T0.05intron_variantRBFOX14e-06Tier 4: intronic/intergenic
rs14848731845627020A>C,G0.05missense_variantSLC14A24e-06Tier 1: coding
rs573615433172494354A>G,T0.05intergenic_variantGHSR - TNFSF105e-06Tier 4: intronic/intergenic
rs677699114116685914C>A,G0.05intergenic_variantACTN4P1 - RNU6-119P6e-06Tier 4: intronic/intergenic
rs739732831876045951A>C,T0.05intergenic_variantLINC01898 - LINC018936e-06Tier 4: intronic/intergenic
rs101213669115481743T>A,C,G0.05intron_variantDELEC1 - U27e-06Tier 4: intronic/intergenic
rs73327261387498629G>A0.05intron_variantMIR4500HG7e-06Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SPARTOrphanet:101000Autosomal recessive spastic paraplegia type 20
CCNOOrphanet:244Primary ciliary dyskinesia
STEAP3Orphanet:300298Severe congenital hypochromic anemia with ringed sideroblasts
DOCK3Orphanet:528084Non-specific syndromic intellectual disability
MCIDASOrphanet:244Primary ciliary dyskinesia
GHSROrphanet:314811Short stature due to GHSR deficiency

Cohort genes → proteins

38 cohort genes, 36 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only38

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SLC14A2HGNC:10919ENSG00000132874Q15849Urea transporter 2gwas
TNFSF10HGNC:11925ENSG00000121858P50591Tumor necrosis factor ligand superfamily member 10gwas
FAM78BHGNC:13495ENSG00000188859Q5VT40Protein FAM78Bgwas
CCNA1HGNC:1577ENSG00000133101P78396Cyclin-A1gwas
DHX29HGNC:15815ENSG00000067248Q7Z478ATP-dependent RNA helicase DHX29gwas
CDK1HGNC:1722ENSG00000170312P06493Cyclin-dependent kinase 1gwas
RIMS2HGNC:17283ENSG00000176406Q9UQ26Regulating synaptic membrane exocytosis protein 2gwas
CDH6HGNC:1765ENSG00000113361P55285Cadherin-6gwas
RBFOX1HGNC:18222ENSG00000078328Q9NWB1RNA binding protein fox-1 homolog 1gwas
COTL1HGNC:18304ENSG00000103187Q14019Coactosin-like proteingwas
SPARTHGNC:18514ENSG00000133104Q8N0X7Spartingwas
CCNOHGNC:18576ENSG00000152669P22674Cyclin-Ogwas
DDX4HGNC:18700ENSG00000152670Q9NQI0Probable ATP-dependent RNA helicase DDX4gwas
MTREXHGNC:18734ENSG00000039123P42285Exosome RNA helicase MTR4gwas
CDC20BHGNC:24222ENSG00000164287Q86Y33Cell division cycle protein 20 homolog Bgwas
STEAP3HGNC:24592ENSG00000115107Q658P3Metalloreductase STEAP3gwas
C3orf18HGNC:24837ENSG00000088543Q9UK00Uncharacterized protein C3orf18gwas
RASGEF1BHGNC:24881ENSG00000138670Q0VAM2Ras-GEF domain-containing family member 1Bgwas
HEMK1HGNC:24923ENSG00000114735Q9Y5R4MTRF1L release factor glutamine methyltransferasegwas
NIPAL2HGNC:25854ENSG00000104361Q9H841NIPA-like protein 2gwas
SOHLH2HGNC:26026ENSG00000120669Q9NX45Spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 2gwas
FAM53BHGNC:28968ENSG00000189319Q14153Protein FAM53Bgwas
MEAK7HGNC:29325ENSG00000140950Q6P9B6MTOR-associated protein MEAK7gwas
DOCK3HGNC:2989ENSG00000088538Q8IZD9Dedicator of cytokinesis protein 3gwas
EFNA5HGNC:3225ENSG00000184349P52803Ephrin-A5gwas
GPX8HGNC:33100ENSG00000164294Q8TED1Probable glutathione peroxidase 8gwas
SERTM1HGNC:33792ENSG00000180440A2A2V5Serine-rich and transmembrane domain-containing protein 1gwas
ESM1HGNC:3466ENSG00000164283Q9NQ30Endothelial cell-specific molecule 1gwas
FGF18HGNC:3674ENSG00000156427O76093Fibroblast growth factor 18gwas
MIR1973HGNC:37061ENSG00000284253microRNA 1973gwas
RANP6HGNC:39861ENSG00000213370RAN pseudogene 6gwas
SPART-AS1HGNC:39933ENSG00000120664P0CW21Putative uncharacterized protein SPART-AS1gwas
MCIDASHGNC:40050ENSG00000234602D6RGH6Multicilingwas
GHSRHGNC:4267ENSG00000121853Q92847Growth hormone secretagogue receptor type 1gwas
NCOR2HGNC:7673ENSG00000196498Q9Y618Nuclear receptor corepressor 2gwas
OR3A1HGNC:8282ENSG00000180090P47881Olfactory receptor 3A1gwas
OR3A2HGNC:8283ENSG00000221882P47893Olfactory receptor 3A2gwas
PLPP1HGNC:9228ENSG00000067113O14494Phospholipid phosphatase 1gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SLC14A2Urea transporter 2Mediates the transport of urea driven by a concentration gradient across the cell membrane of the renal inner medullary collecting duct which is critical to the urinary concentrating mechanism.
TNFSF10Tumor necrosis factor ligand superfamily member 10Cytokine that binds to TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and possibly also to TNFRSF11B/OPG.
CCNA1Cyclin-A1May be involved in the control of the cell cycle at the G1/S (start) and G2/M (mitosis) transitions.
DHX29ATP-dependent RNA helicase DHX29ATP-binding RNA helicase involved in translation initiation.
CDK1Cyclin-dependent kinase 1Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition via association with multiple interphase cyclins.
RIMS2Regulating synaptic membrane exocytosis protein 2Rab effector involved in exocytosis.
CDH6Cadherin-6Cadherins are calcium-dependent cell adhesion proteins.
RBFOX1RNA binding protein fox-1 homolog 1RNA-binding protein that regulates alternative splicing events by binding to 5’-UGCAUGU-3’ elements.
COTL1Coactosin-like proteinBinds to F-actin in a calcium-independent manner.
SPARTSpartinLipophagy receptor that plays an important role in lipid droplet (LD) turnover in motor neurons.
CCNOCyclin-OSpecifically required for generation of multiciliated cells, possibly by promoting a cell cycle state compatible with centriole amplification and maturation.
DDX4Probable ATP-dependent RNA helicase DDX4ATP-dependent RNA helicase required during spermatogenesis.
MTREXExosome RNA helicase MTR4Catalyzes the ATP-dependent unwinding of RNA duplexes with a single-stranded 3’ RNA extension.
CDC20BCell division cycle protein 20 homolog BProtein regulator of centriole-deuterosome disengagement and subsequently participates in the ciliogenesis in multiciliated cells (MCCs).
STEAP3Metalloreductase STEAP3Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the membrane.
RASGEF1BRas-GEF domain-containing family member 1BGuanine nucleotide exchange factor (GEF) with specificity for RAP2A, it doesn’t seems to activate other Ras family proteins (in vitro).
HEMK1MTRF1L release factor glutamine methyltransferaseN5-glutamine methyltransferase responsible for the methylation of the glutamine residue in the universally conserved GGQ motif of the mitochondrial translation release factors MTRF1, MTRF1L, MRPL58/ICT1 and MTRFR.
SOHLH2Spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 2Transcription regulator of both male and female germline differentiation.
FAM53BProtein FAM53BActs as a regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) nuclear localization.
MEAK7MTOR-associated protein MEAK7Activates an alternative mTOR signaling through RPS6KB2 activation and EIF4EBP1 repression to regulate cell proliferation and migration.
DOCK3Dedicator of cytokinesis protein 3Potential guanine nucleotide exchange factor (GEF).
EFNA5Ephrin-A5Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development.
ESM1Endothelial cell-specific molecule 1Involved in angiogenesis; promotes angiogenic sprouting.
FGF18Fibroblast growth factor 18Plays an important role in the regulation of cell proliferation, cell differentiation and cell migration.
MCIDASMulticilinTranscription regulator specifically required for multiciliate cell differentiation.
GHSRGrowth hormone secretagogue receptor type 1G-protein-coupled receptor specific to ghrelin, an appetite-regulating peptide hormone commonly found in stomach.
NCOR2Nuclear receptor corepressor 2Transcriptional corepressor that mediates the transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access of the basal transcription.
OR3A1Olfactory receptor 3A1Odorant receptor.
OR3A2Olfactory receptor 3A2Odorant receptor.
PLPP1Phospholipid phosphatase 1Magnesium-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…

Protein-family classification

Druggable: 9 · Difficult: 5 · Unknown: 24 · Druggable fraction: 0.24

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
Transporter12.0×0.686
GPCR31.9×0.686
Enzyme (other)41.3×0.686
Other/Unknown241.1×0.686
Scaffold/PPI20.9×0.855
Kinase10.7×0.855
Transcription factor30.7×0.855

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SLC14A2TransporteryesUrea_transporter, Ammonium/urea_transptr
TNFSF10Other/UnknownnoTNF_dom, Tumour_necrosis_fac-like_dom, TNF_ligand_10/11
FAM78BOther/UnknownnoFAM78
CCNA1Other/UnknownnoCyclin_C-dom, Cyclin_N, Cyclin-like_dom
DHX29Other/UnknownnoHelicase_C-like, DNA/RNA_helicase_DEAH_CS, Helicase-assoc_dom
CDK1Kinaseyes2.7.11.22Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
RIMS2Transcription factornoC2_dom, PDZ, Rab_BD
CDH6Other/UnknownnoCadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf
RBFOX1Other/UnknownnoRRM_dom, Nucleotide-bd_a/b_plait_sf, RBFOX1-3
COTL1Other/UnknownnoADF-H, ADF-H/Gelsolin-like_dom_sf
SPARTOther/UnknownnoMIT_dom, Senescence/spartin_C, MIT_dom_sf
CCNOEnzyme (other)yes3.2.2.27Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
DDX4Enzyme (other)yes3.6.4.13RNA-helicase_DEAD-box_CS, Helicase_C-like, DEAD/DEAH_box_helicase_dom
MTREXOther/UnknownnoHelicase_C-like, DEAD/DEAH_box_helicase_dom, Ski2/MTR4_C
CDC20BScaffold/PPInoWD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
STEAP3Other/UnknownnoFe3_Rdtase_TM_dom, P5C_Rdtase_cat_N, NAD(P)-bd_dom_sf
C3orf18Other/UnknownnoC3orf18-like
RASGEF1BOther/UnknownnoRas-like_Gua-exchang_fac_N, RASGEF_cat_dom, Ras-like_GEF
HEMK1Enzyme (other)yes2.1.1.297DNA_methylase_N6_adenine_CS, N4/N6-MTase_EcoPI_Mod-like, HemK-like
NIPAL2Other/UnknownnoMg_trans_NIPA, EmrE-like
SOHLH2Transcription factornobHLH_dom, HLH_DNA-bd_sf, TCFL5/SOLH1/2
FAM53BOther/UnknownnoFAM53
MEAK7Other/UnknownnoTLDc_dom
DOCK3Scaffold/PPInoSH3_domain, ARM-type_fold, DOCK
EFNA5Other/UnknownnoEphrin_RBD, Cupredoxin, Ephrin_CS
GPX8Enzyme (other)yes1.11.1.9Glutathione_peroxidase, Glut_perox_Gpx7, GPX_CS
SERTM1Other/UnknownnoSERTM
ESM1Other/UnknownnoIGFBP-like, Growth_fac_rcpt_cys_sf, ESM1
FGF18Other/UnknownnoFibroblast_GF_fam, IL1/FGF
MIR1973Other/Unknownno
RANP6Other/Unknownno
SPART-AS1Other/Unknownno
MCIDASOther/UnknownnoGeminin/Multicilin
GHSRGPCRyesGPCR_Rhodpsn, GHS-R/MTLR, GPCR_Rhodpsn_7TM
NCOR2Transcription factornoSANT/Myb, Homeodomain-like_sf, SANT_dom
OR3A1GPCRyesGPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
OR3A2GPCRyesGPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
PLPP1Other/UnknownnoPAP2/HPO, PAP2/HPO_sf, PAP-like

Expression context

Cohort genes with no expression data: 0.

32 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)2
broad (>20)35
unknown1

Top tissues across cohort

TissueCohort genes
primordial germ cell in gonad6
secondary oocyte6
male germ line stem cell (sensu Vertebrata) in testis6
ganglionic eminence4
monocyte3
Brodmann (1909) area 233
right testis3
sperm3
right lobe of liver3
hair follicle2
nasal cavity epithelium2
cortical plate2
endothelial cell2
ventricular zone2
middle temporal gyrus2
olfactory bulb2
calcaneal tendon2
oocyte2
sural nerve2
right lobe of thyroid gland2

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SLC14A2100tissue_specificmarkerprimordial germ cell in gonad, hair follicle, right adrenal gland
TNFSF10285ubiquitousmarkernasal cavity epithelium, urethra, monocyte
FAM78B164broadyesendothelial cell, Brodmann (1909) area 23, cortical plate
CCNA1180broadmarkersperm, left testis, right testis
DHX29294ubiquitousmarkeresophagus squamous epithelium, palpebral conjunctiva, secondary oocyte
CDK1226ubiquitousmarkerventricular zone, ganglionic eminence, embryo
RIMS2198broadmarkerlateral nuclear group of thalamus, endothelial cell, middle temporal gyrus
CDH6228broadmarkerolfactory bulb, type B pancreatic cell, tongue squamous epithelium
RBFOX1220broadmarkermiddle temporal gyrus, Brodmann (1909) area 23, cortical plate
COTL1283ubiquitousmarkermonocyte, leukocyte, granulocyte
SPART286ubiquitousmarkercalcaneal tendon, adrenal tissue, left ovary
CCNO172broadmarkeroocyte, secondary oocyte, epithelium of bronchus
DDX4113tissue_specificmarkersecondary oocyte, right testis, sperm
MTREX292ubiquitousmarkercalcaneal tendon, sural nerve, primordial germ cell in gonad
CDC20B50tissue_specificmarkersecondary oocyte, buccal mucosa cell, primordial germ cell in gonad
STEAP3259ubiquitousmarkerright lobe of liver, liver, dorsal root ganglion
C3orf18258ubiquitousmarkerright hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
RASGEF1B164ubiquitousmarkerganglionic eminence, right lobe of liver, monocyte
HEMK1264ubiquitousmarkerright uterine tube, right lobe of thyroid gland, right lobe of liver
NIPAL2248ubiquitousmarkerupper arm skin, upper leg skin, nasal cavity epithelium
SOHLH2151tissue_specificyessecondary oocyte, oocyte, sperm
FAM53B284ubiquitousmarkerolfactory bulb, ventricular zone, ganglionic eminence
MEAK7218ubiquitousmarkercervix squamous epithelium, gingival epithelium, squamous epithelium
DOCK3203broadmarkerfrontal pole, Brodmann (1909) area 10, paraflocculus
EFNA5258ubiquitousmarkerhair follicle, Brodmann (1909) area 23, cervix squamous epithelium
GPX8227ubiquitousmarkerstromal cell of endometrium, oviduct epithelium, tibia
SERTM1160broadmarkergerminal epithelium of ovary, left uterine tube, fallopian tube
ESM1166broadmarkerislet of Langerhans, right lung, male germ line stem cell (sensu Vertebrata) in testis
FGF18172broadmarkertendon of biceps brachii, heart right ventricle, vena cava
MIR1973yes

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

SymbolInteractor count
CDK19,095
GPX84,579
NCOR24,453
MTREX3,982
CCNA13,949
FGF183,769
DDX43,472
RBFOX12,990
CDC20B2,956
DHX292,847

Intra-cohort edges

ABSources
CCNA1CDK1string_interaction
CCNOCDC20Bstring_interaction
CCNOCDK1biogrid_interaction
CCNOMCIDASstring_interaction
CDC20BMCIDASstring_interaction
GPX8SERTM1intact

Structural data

PDB: 19 · AlphaFold-only: 17 · No structure: 2

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
NCOR2Q9Y61836
CDK1P0649313
MTREXP4228511
GHSRQ9284710
SLC14A2Q158499
TNFSF10P505917
COTL1Q140196
EFNA5P528036
PLPP1O144945
RBFOX1Q9NWB14
MEAK7Q6P9B63
DHX29Q7Z4782
RIMS2Q9UQ262
SPARTQ8N0X72
STEAP3Q658P32
GPX8Q8TED12
CDH6P552851
FGF18O760931
MCIDASD6RGH61

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
FAM78BQ5VT4095.02
HEMK1Q9Y5R488.08
RASGEF1BQ0VAM287.31
OR3A1P4788187.02
OR3A2P4789385.25
NIPAL2Q9H84179.86
CCNOP2267479.06
DOCK3Q8IZD975.52
ESM1Q9NQ3072.15
SPART-AS1P0CW2170.64
CDC20BQ86Y3369.60
DDX4Q9NQI069.06
CCNA1P7839668.65
SERTM1A2A2V564.26
C3orf18Q9UK0063.61
SOHLH2Q9NX4558.36
FAM53BQ1415352.88

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 244. Enrichment computed across 38 evidence-associated genes (20 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 20 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
R-HSA-1701452285.5×0.004CCNA1, CDK1
G2/M DNA replication checkpoint2126.9×0.013CCNA1, CDK1
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex267.2×0.032CCNA1, CDK1
TP53 Regulates Transcription of Cell Cycle Genes254.4×0.032CCNA1, CDK1
Regulation of TP53 Expression and Degradation251.9×0.032CCNA1, CDK1
G0 and Early G1243.9×0.032CCNA1, CDK1
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint242.3×0.032CCNA1, CDK1
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins240.8×0.032CCNA1, CDK1
APC/C:Cdc20 mediated degradation of mitotic proteins235.7×0.032CCNA1, CDK1
G1/S-Specific Transcription235.7×0.032CCNA1, CDK1
APC/C-mediated degradation of cell cycle proteins233.6×0.032CCNA1, CDK1
Regulation of mitotic cell cycle233.6×0.032CCNA1, CDK1
Regulation of APC/C activators between G1/S and early anaphase230.9×0.033CCNA1, CDK1
Cyclin A/B1/B2 associated events during G2/M transition230.9×0.033CCNA1, CDK1
Regulation of TP53 Degradation229.3×0.034CCNA1, CDK1
G1/S Transition223.3×0.050CCNA1, CDK1
Transcriptional Regulation by TP5339.3×0.055CCNA1, CDK1, STEAP3
Gene expression (Transcription)54.5×0.057CCNA1, CDK1, MTREX, STEAP3, NCOR2
Mitotic G1 phase and G1/S transition218.4×0.066CCNA1, CDK1
Cdc20:Phospho-APC/C mediated degradation of Cyclin A217.3×0.071CCNA1, CDK1
MECP2 regulates transcription factors1114.2×0.087RBFOX1
NTRK2 activates RAC1195.2×0.087DOCK3
E2F mediated regulation of DNA replication181.6×0.087CDK1
FGFR3b ligand binding and activation181.6×0.087FGF18
G2 Phase181.6×0.087CCNA1
Loss of MECP2 binding ability to the NCoR/SMRT complex181.6×0.087NCOR2
Phosphorylation of Emi1171.4×0.087CDK1
Activation of NIMA Kinases NEK9, NEK6, NEK7171.4×0.087CDK1
TRAIL signaling171.4×0.087TNFSF10
Loss of function of MECP2 in Rett syndrome171.4×0.087NCOR2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 32 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
multi-ciliated epithelial cell differentiation2175.5×0.014CCNO, MCIDAS
spermatogenesis66.6×0.033CCNA1, CCNO, DDX4, SOHLH2, MCIDAS, GHSR
pronuclear fusion1526.6×0.039CDK1
regulation of Schwann cell differentiation1526.6×0.039CDK1
regulation of hindgut contraction1526.6×0.039GHSR
negative regulation of collateral sprouting in absence of injury1526.6×0.039SPART
de novo centriole assembly1526.6×0.039CDC20B
positive regulation of hepatocyte growth factor receptor signaling pathway1526.6×0.039ESM1
regulation of attachment of mitotic spindle microtubules to kinetochore1526.6×0.039CDK1
seminiferous tubule development247.9×0.039CCNO, MCIDAS
male meiosis I236.3×0.039CCNA1, DDX4
synaptic membrane adhesion236.3×0.039CDH6, EFNA5
G1/S transition of mitotic cell cycle318.8×0.039CCNA1, CDK1, CCNO
ghrelin secretion1263.3×0.051GHSR
regulation of transmission of nerve impulse1263.3×0.051GHSR
negative regulation of locomotion involved in locomotory behavior1263.3×0.051GHSR
positive regulation of small intestinal transit1263.3×0.051GHSR
regulation of gastric motility1263.3×0.051GHSR
snRNA catabolic process1175.5×0.051MTREX
positive regulation of appetite1175.5×0.051GHSR
collateral sprouting in absence of injury1175.5×0.051SPART
regulation of growth hormone secretion1175.5×0.051GHSR
lipophagy1175.5×0.051SPART
positive regulation of mitotic sister chromatid segregation1175.5×0.051CDK1
regulation of heterochromatin organization1175.5×0.051CDK1
positive regulation of protein localization to lysosome1175.5×0.051MEAK7
positive regulation of small intestine smooth muscle contraction1175.5×0.051GHSR
positive regulation of endothelial cell chemotaxis to fibroblast growth factor1175.5×0.051FGF18
ERK1 and ERK2 cascade219.9×0.051CDK1, FGF18
cell division45.8×0.051CCNA1, CDK1, SPART, CCNO

Therapeutics

Drugs indicated for this disease

0 approved, 9 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
BiperidenPhase 3 (in late-stage trials)
BuprenorphinePhase 3 (in late-stage trials)
MethadonePhase 3 (in late-stage trials)
ModafinilPhase 3 (in late-stage trials)
NaltrexonePhase 3 (in late-stage trials)
NefazodonePhase 3 (in late-stage trials)
PergolidePhase 3 (in late-stage trials)
SelegilinePhase 3 (in late-stage trials)
TopiramatePhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): (D)-Serine, Acamprosate, Acetylcysteine, Amantadine, Aprepitant, Aripiprazole, Baclofen, Benztropine, Bupropion, Buspirone, Cabergoline, Caffeine, Candesartan, Cannabidiol, Carbamazepine, Carvedilol, Citalopram, Clavulanic Acid, Cocaine, Cycloserine, Desipramine, Dextroamphetamine, Diphenhydramine, Disulfiram, Donepezil, Doxazosin, Entacapone, Escitalopram, Fluoxetine, Galantamine, Gepirone, Guanfacine, Ketamine, Labetalol, Lactose, Anhydrous, Lamotrigine, Levetiracetam, Levodopa, Lidocaine, Lisdexamfetamine, Lorazepam, Lorcaserin, Mazindol, Memantine, Methylphenidate, Mifepristone, Mirtazapine, Nimodipine, Ondansetron, Oxytocin, Pemoline, Perphenazine, Progesterone, Propranolol, Psilocybin, Reserpine, Risperidone, Ropinirole, Sertraline, Sodium Chloride, Tacrine, Tiagabine, Tryptophan, Varenicline, Vigabatrin, Yohimbine.

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 5 · Phased (≥1): 5 · Undrugged: 33

Druggability breadth: 8 of 38 evidence-associated genes (21%) 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
CCNA1PALBOCICLIB
CDK1PALBOCICLIB
GHSRBEPRIDIL
NCOR2BENZBROMARONE

Top cohort targets by molecule count

SymbolMoleculesMax phase
GHSR1134
CDK1604
CCNA1204
NCOR2154
MTREX23
SLC14A200
TNFSF1000
FAM78B00
DHX2900
RIMS200

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
PALBOCICLIB4CCNA1, CDK1
PACRITINIB4CCNA1
QUIZARTINIB4CCNA1
ABEMACICLIB4CDK1
RUCAPARIB4CDK1
DABRAFENIB4CDK1
BEPRIDIL4GHSR
DIBUCAINE4GHSR
RIMONABANT4GHSR
ARIPIPRAZOLE4GHSR
IDARUBICIN4GHSR
DICYCLOMINE4GHSR
SAQUINAVIR4GHSR
ATAZANAVIR4GHSR
PONATINIB4GHSR
DULOXETINE4GHSR
VILANTEROL4GHSR
TIOCONAZOLE4GHSR
DESERPIDINE4GHSR
THIOTHIXENE4GHSR
BUCLIZINE4GHSR
CINACALCET4GHSR
PYRVINIUM4GHSR
INDOCYANINE GREEN ACID FORM4GHSR
NAFARELIN4GHSR
SERTINDOLE4GHSR
FEDRATINIB4GHSR
CLOFAZIMINE4GHSR
ROTIGOTINE4GHSR
FLUNITRAZEPAM4GHSR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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

SymbolAssaysType breakdown
CDK11,262Binding:1242, ADMET:11, Functional:8, Toxicity:1
GHSR373Functional:238, Binding:135
CCNA1336Binding:333, Functional:2, Toxicity:1
NCOR2181Binding:167, ADMET:11, Functional:2, Toxicity:1
CCNO22Binding:22
MTREX9Binding:9
DHX296Binding:6
TNFSF103Functional:2, Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
CDK12.7.11.22cyclin-dependent kinase
CCNO3.2.2.27uracil-DNA glycosylase
DDX43.6.4.13RNA helicase
HEMK12.1.1.297peptide chain release factor N5-glutamine methyltransferase
GPX81.11.1.9glutathione peroxidase

Cohort genes with high screening signal

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

SymbolChEMBL assays
CCNA1336
CDK11,262
GHSR373
NCOR2181

Pharmacogenomics

Cohort genes with a PharmGKB record: 36; 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)
PALBOCICLIB4CCNA1, CDK1
PACRITINIB4CCNA1
QUIZARTINIB4CCNA1
ABEMACICLIB4CDK1
RUCAPARIB4CDK1
DABRAFENIB4CDK1
BEPRIDIL4GHSR
DIBUCAINE4GHSR
RIMONABANT4GHSR
ARIPIPRAZOLE4GHSR
IDARUBICIN4GHSR
DICYCLOMINE4GHSR
SAQUINAVIR4GHSR
ATAZANAVIR4GHSR
PONATINIB4GHSR
DULOXETINE4GHSR
VILANTEROL4GHSR
TIOCONAZOLE4GHSR
DESERPIDINE4GHSR
THIOTHIXENE4GHSR
BUCLIZINE4GHSR
CINACALCET4GHSR
PYRVINIUM4GHSR
INDOCYANINE GREEN ACID FORM4GHSR
NAFARELIN4GHSR
SERTINDOLE4GHSR
FEDRATINIB4GHSR
CLOFAZIMINE4GHSR
ROTIGOTINE4GHSR
FLUNITRAZEPAM4GHSR

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)4CCNA1, CDK1, GHSR, NCOR2
BPhased (≥1) drug, not yet approved1MTREX
CDruggable family + PDB, no drug2SLC14A2, GPX8
DDruggable family + AlphaFold only, no drug5CCNO, DDX4, HEMK1, OR3A1, OR3A2
EDifficult family or no structure, no drug26TNFSF10, FAM78B, DHX29, RIMS2, CDH6, RBFOX1, COTL1, SPART, CDC20B, STEAP3 (+16 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
SLC14A20—
TNFSF103—
FAM78B0—
DHX296—
RIMS20—
CDH60—
RBFOX10—
COTL10—
SPART0—
CCNO22—
DDX40—
CDC20B0—
STEAP30—
C3orf180—
RASGEF1B0—
HEMK10—
NIPAL20—
SOHLH20—
FAM53B0—
MEAK70—
DOCK30—
EFNA50—
GPX80—
SERTM10—
ESM10—
FGF180—
MIR19730—
RANP60—
SPART-AS10—
MCIDAS0—

Clinical trials & evidence

Clinical trials

Clinical trials: 210.

Phase distribution (across all retrieved trials)

PhaseTrials
PHASE279
Not specified61
PHASE125
PHASE1/PHASE212
PHASE2/PHASE311
PHASE48
PHASE37
EARLY_PHASE17

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00223210PHASE4COMPLETEDAn Add-On Trial of Quetiapine in Patients With Bipolar Disorder and Cocaine Dependence
NCT00280293PHASE4COMPLETEDLamotrigine add-on Therapy for Bipolar Disorder and Cocaine Dependency
NCT00495183PHASE4UNKNOWNEfficacy of Caffeine, With and Without Biperiden, as a Maintenance Treatment for Cocaine Dependence
NCT00619723PHASE4COMPLETEDCiticoline for Bipolar 1 Disorder and Cocaine Dependence
NCT02134002PHASE4WITHDRAWNA PET Exploration of the Mechanism of Action of Dopamine Beta-hydroxylase Inhibition in Cocaine Addicts
NCT02626494PHASE4COMPLETEDNeurobiological Adaptations and Pharmacological Interventions in Cocaine Addiction
NCT03018236PHASE4UNKNOWNEffect of N-acetylcysteine on Alcohol and Cocaine Use Disorders: A Double-Blind Randomized Controlled Trial.
NCT06159387PHASE4UNKNOWNRandomized, Double-blind, Placebo-controlled Cannabis Extract x Placebo for Cocaine Addicts
NCT00061087PHASE2/PHASE3COMPLETEDTreatment of Adult Attention Deficit Hyperactivity Disorder (ADHD) in Methadone Patients - 1
NCT00167232PHASE3COMPLETEDNaltrexone in Two Models of Psychosocial Treatments for Cocaine and Alcohol Dependence
NCT00218660PHASE3COMPLETEDNaltrexone in Two Models of Psychosocial Treatments for Cocaine and Alcohol Dependence - 1
NCT00223236PHASE3COMPLETEDTrial of Citicoline Therapy in Patients With Mania or Hypomania and Cocaine Abuse/Dependence
NCT00448825PHASE3UNKNOWNNovel Pharmacotherapy for Dual Dependence
NCT00553319PHASE2/PHASE3COMPLETEDStudy of Adderall-XR for the Treatment of Adult Attention Deficit Hyperactivity Disorder and Cocaine Dependence
NCT00632099PHASE2/PHASE3COMPLETEDProgesterone Treatment for Cocaine-dependent Women: A Pilot Study
NCT00701532PHASE3COMPLETEDBrain Imaging Study of the Effects of Modafinil in Cocaine Addiction
NCT00732901PHASE2/PHASE3COMPLETEDClinical Neurobiology of Serotonin and Addiction
NCT01077024PHASE3COMPLETEDSmoking-Cessation and Stimulant Treatment (S-CAST)
NCT01134198PHASE2/PHASE3COMPLETEDInvestigation of Mifepristone (RU486) on Stress Sensitivity and Relapse Prevention in Cocaine Dependent Patients
NCT01251393PHASE3COMPLETEDCocaine/Crack and Reduction of Compulsion With Biperiden
NCT01281202PHASE2/PHASE3COMPLETEDVigabatrin for the Treatment of Cocaine Dependency
NCT01402492PHASE2/PHASE3COMPLETEDCocaine Use Reduction With Buprenorphine
NCT01468012PHASE2/PHASE3COMPLETEDImaging the Neurobiology of Behavioral and Medication Treatment for Cocaine Dependence
NCT01811940PHASE2/PHASE3COMPLETEDMulticenter Trial of Combined Pharmacotherapy to Treat Cocaine Dependence
NCT02111798PHASE2/PHASE3COMPLETEDBupropion-Enhanced Contingency Management (CM) for Cocaine Dependence
NCT02255357PHASE2/PHASE3COMPLETEDInvestigation of Intranasal Oxytocin on Relapse Risk in Cocaine-dependent Patients.
NCT05562349PHASE2ACTIVE_NOT_RECRUITINGClavulanic Acid for the Treatment of Cocaine Use Disorder
NCT06125054PHASE2RECRUITINGKetamine and Neurofeedback-Training: Effects on Neuroplasticity in Cocaine Addiction
NCT00123383PHASE2UNKNOWNRandomised Placebo-Controlled Trial of Modafinil for Cocaine Dependence
NCT00149630PHASE2COMPLETEDPharmacogenetics of Disulfiram for Cocaine
NCT00167245PHASE2COMPLETEDTopiramate for Alcohol and Cocaine Dependence
NCT00167258PHASE2COMPLETEDEffectiveness and Costs of Enhanced Cocaine Treatments
NCT00218387PHASE2COMPLETEDModafinil Combined With Cognitive Behavior Therapy to Treat Cocaine Addiction - 1
NCT00218491PHASE2COMPLETEDEffectiveness of N-Acetylcysteine (NAC) in Treating Cocaine Dependent Individuals - 1
NCT00218569PHASE2COMPLETEDCombined Treatment for Cocaine-Alcohol Dependence - 1
NCT00227812PHASE2COMPLETEDIntegrated Treatment for Cocaine and Mood Disorders - 1
NCT00240110PHASE1/PHASE2COMPLETEDValproate Efficacy in Cocaine-Bipolar Comorbidity
NCT00249444PHASE2COMPLETEDMirtazapine for Treating Cocaine Dependent Individuals Who Also Suffer From Depression
NCT00297505PHASE2COMPLETEDSerotonin, Impulsivity, and Cocaine Dependence Treatment
NCT00322309PHASE2COMPLETEDEfficacy of Mirtazapine in Depressed Cocaine Dependent Subjects

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
COCAINE415
DOXAZOSIN415
CITALOPRAM49
NALTREXONE49
MODAFINIL48
CARBIDOPA ANHYDROUS46
VIGABATRIN46
DISULFIRAM45
BUPROPION43
DEXTROAMPHETAMINE43
LEVODOPA43
LISDEXAMFETAMINE43
ROPINIROLE43
SODIUM CHLORIDE43
ACETYLCYSTEINE42
BIPERIDEN42
BUSPIRONE42
CAFFEINE42
CLAVULANIC ACID42
MIRTAZAPINE42
VALPROIC ACID42
ACAMPROSATE41
ALCOHOL41
AMPHETAMINE41
CABERGOLINE41
CANNABIDIOL41
GALANTAMINE41
LAMOTRIGINE41
LITHIUM CARBONATE41
LORAZEPAM41

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 73

This page pulls from 73 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncicd10cmicd11intactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot