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Opiate dependence

disease
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Also known as opioid dependenceopioid type dependence

Summary

Opiate dependence (MONDO:0005530) is a disease with 11 cohort genes (288 GWAS associations across 14 studies) and 249 clinical trials. Top therapeutic interventions include buprenorphine, naltrexone, and naloxone.

At a glance

  • Cohort genes: 11
  • GWAS associations: 288
  • Clinical trials: 249

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameopiate dependence
Mondo IDMONDO:0005530
EFOEFO:0005611
MeSHD009293
DOIDDOID:2559
ICD-10-CMF11.2
SNOMED CT75544000
UMLSC0524662
MedGen99372
Is cancer (heuristic)no

Also known as: opioid dependence · opioid type dependence

Data availability: 288 GWAS associations (14 studies).

Disease family

An umbrella term covering 2 Mondo subtypes.

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

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

Subtypes (2): heroin dependence, morphine dependence

Genetics & variants

GWAS landscape

288 GWAS associations across 14 studies. Top hits map to 21 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs23669292e-09ADGRV1?0.11
rs94785003e-09OPRM1C1.14
rs107995904e-09CNIH3G1.56
rs19706068e-09GAPDHP15 - RBBP4P4G0.06
rs15572199e-09GAPDHP15 - RBBP4P4C0.06
rs283869169e-09GPRIN3 - SNCAT0.17
rs124421831e-08RGMA - SEPHS1P2T0.44
rs2011238203e-08SRP72P1 - LINC02837T5.55
rs24430664e-08ADGRV1?0.1
rs24601864e-08ADGRV1?0.1
rs24601874e-08ADGRV1?0.1
rs24430654e-08ADGRV1?0.1
rs24430644e-08ADGRV1?0.1
rs133335824e-08CTCF-DTC0.8
rs20302725e-08ADGRV1?0.1
rs22222435e-08ADGRV1?0.1
rs24430675e-08ADGRV1?0.1
rs80367478e-08RGMA - SEPHS1P2?0.39
rs113734068e-08OPRM1?0.17
rs596752431e-07TACC2A0.13
rs1143418231e-07GRIN2B?
rs48604391e-07LINC02619T0.8
rs1153913351e-07LINC00474 - PAPPAT1.72
rs1445033881e-07NIPAL1?0.59
rs43016371e-07RPLP0P5 - RPL7AP81?0.27
rs18720522e-07RGMA - SEPHS1P2?0.37
rs754498252e-07TACC2G0.13
rs173005322e-07CARTPT - MAP1BT0.06
rs80639462e-07FTO?
rs1423520322e-07SPINDOC?2.82

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90244554Gaddis N20227,281297,550Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond.
GCST90244556Gaddis N20227,281297,550Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond.
GCST90244557Gaddis N20223,85612,203Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond.
GCST009419Yang BZ20192,6032,341Genomewide Gene-by-Sex Interaction Scans Identify ADGRV1 for Sex Differences in Opioid Dependent African Americans.
GCST012220Sherva R20212,3400Genome-wide association study of phenotypes measuring progression from first cocaine or opioid use to dependence reveals novel risk genes.
GCST008424Brick LA20192,1201,944Characterization of DSM-IV Opioid Dependence Among Individuals of European Ancestry.
GCST012221Sherva R20211,3070Genome-wide association study of phenotypes measuring progression from first cocaine or opioid use to dependence reveals novel risk genes.
GCST012222Sherva R20211,3070Genome-wide association study of phenotypes measuring progression from first cocaine or opioid use to dependence reveals novel risk genes.
GCST90043725Jiang L20211,303455,045A generalized linear mixed model association tool for biobank-scale data.
GCST009854Polimanti R20201,2311,297Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic50

MAF distribution

BucketVariants
common (>=0.05)41
low_freq (0.01-0.05)4
rare (<0.01)0
unknown5

Functional consequences

ConsequenceCount
intron_variant39
intergenic_variant8
unknown3

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs2366929590730817T>A,C,G0.05intron_variantADGRV12e-09Tier 4: intronic/intergenic
rs94785006154057088T>C0.05intron_variantOPRM13e-09Tier 4: intronic/intergenic
rs107995901224634780G>A0.49intron_variantCNIH34e-09Tier 4: intronic/intergenic
rs1970606658042294G>A,T0.05intron_variantGAPDHP15 - RBBP4P48e-09Tier 4: intronic/intergenic
rs1557219658044647C>A,T0.05intron_variantGAPDHP15 - RBBP4P49e-09Tier 4: intronic/intergenic
rs28386916489432039T>A,G0.05intron_variantGPRIN3 - SNCA9e-09Tier 4: intronic/intergenic
rs124421831593204756C>G,T0.41intron_variantRGMA - SEPHS1P21e-08Tier 4: intronic/intergenic
rs2011238201849498978TAAACAAAAACA>T,TAAACAAAAACAAAACAAAAACA0.019intergenic_variantSRP72P1 - LINC028373e-08Tier 4: intronic/intergenic
rs2443066590738967A>G,T0.05intron_variantADGRV14e-08Tier 4: intronic/intergenic
rs2460186590741163A>G,T0.05intron_variantADGRV14e-08Tier 4: intronic/intergenic
rs2460187590742633G>C,T0.05intron_variantADGRV14e-08Tier 4: intronic/intergenic
rs2443065590757239A>G,T0.05intron_variantADGRV14e-08Tier 4: intronic/intergenic
rs2443064590757463T>A,C0.05intron_variantADGRV14e-08Tier 4: intronic/intergenic
rs133335821667515644T>C0.05intergenic_variantCTCF-DT4e-08Tier 4: intronic/intergenic
rs2030272590730025C>A,G,T0.05intron_variantADGRV15e-08Tier 4: intronic/intergenic
rs2222243590737880A>C,T0.05intron_variantADGRV15e-08Tier 4: intronic/intergenic
rs2443067590738485A>G0.05intron_variantADGRV15e-08Tier 4: intronic/intergenic
rs80367471593209226G>A0.05intron_variantRGMA - SEPHS1P28e-08Tier 4: intronic/intergenic
rs113734066154059585TAAAAA>T,TAAAA,TAAAAAA,TAAAAAAA,TAAAAAAAA0.05intron_variantOPRM18e-08Tier 4: intronic/intergenic
rs5967524310122011107C>A0.05intron_variantTACC21e-07Tier 4: intronic/intergenic
rs1143418231213933717C>Tintron_variantGRIN2B1e-07Tier 4: intronic/intergenic
rs4860439458960564C>A,G,T0.31intron_variantLINC026191e-07Tier 4: intronic/intergenic
rs1153913359115944964C>A,T0.03intron_variantLINC00474 - PAPPA1e-07Tier 4: intronic/intergenic
rs144503388447924097C>T0.05intergenic_variantNIPAL11e-07Tier 4: intronic/intergenic
rs43016371220391140C>G,T0.05intergenic_variantRPLP0P5 - RPL7AP811e-07Tier 4: intronic/intergenic
rs18720521593209649T>A,C,G0.05intron_variantRGMA - SEPHS1P22e-07Tier 4: intronic/intergenic
rs7544982510122010374C>A,G0.05intron_variantTACC22e-07Tier 4: intronic/intergenic
rs17300532572084528C>T0.05intergenic_variantCARTPT - MAP1B2e-07Tier 4: intronic/intergenic
rs80639461653779586C>T0.05intron_variantFTO2e-07Tier 4: intronic/intergenic
rs1423520321163817544T>Cintron_variantSPINDOC2e-07Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
BMPR1BOrphanet:2098Acromesomelic dysplasia, Grebe type
BMPR1BOrphanet:2639Fibular aplasia-complex brachydactyly syndrome
BMPR1BOrphanet:93384Brachydactyly type C
BMPR1BOrphanet:93388Brachydactyly type A1
BMPR1BOrphanet:93396Brachydactyly type A2
AASSOrphanet:2203Hyperlysinemia
AASSOrphanet:3124Saccharopinuria
FTOOrphanet:210144Lethal polymalformative syndrome, Boissel type
GRIN2BOrphanet:589547GRIN2B-related developmental delay, intellectual disability and autism spectrum disorder
GRIN2BOrphanet:697160Infantile epileptic spasms syndrome

Cohort genes → proteins

11 cohort genes, 11 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only11

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
BMPR1BHGNC:1077ENSG00000138696O00238Bone morphogenetic protein receptor type-1Bgwas
TACC2HGNC:11523ENSG00000138162O95359Transforming acidic coiled-coil-containing protein 2gwas
AASSHGNC:17366ENSG00000008311Q9UDR5Alpha-aminoadipic semialdehyde synthase, mitochondrialgwas
LINC00474HGNC:23367ENSG00000204148Q9P2X8Putative uncharacterized protein encoded by LINC00474gwas
FTOHGNC:24678ENSG00000140718Q9C0B1Alpha-ketoglutarate-dependent dioxygenase FTOgwas
CNIH3HGNC:26802ENSG00000143786Q8TBE1Protein cornichon homolog 3gwas
LINC00299HGNC:27940ENSG00000236790Q6ZSB3Putative uncharacterized protein encoded by LINC00299gwas
RGMAHGNC:30308ENSG00000182175Q96B86Repulsive guidance molecule Agwas
GRIN2BHGNC:4586ENSG00000273079Q13224Glutamate receptor ionotropic, NMDA 2Bgwas
KRT8HGNC:6446ENSG00000170421P05787Keratin, type II cytoskeletal 8gwas
MAPK8HGNC:6881ENSG00000107643P45983Mitogen-activated protein kinase 8gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
BMPR1BBone morphogenetic protein receptor type-1BOn ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.
TACC2Transforming acidic coiled-coil-containing protein 2Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome.
AASSAlpha-aminoadipic semialdehyde synthase, mitochondrialBifunctional enzyme that catalyzes the first two steps in lysine degradation.
FTOAlpha-ketoglutarate-dependent dioxygenase FTORNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis.
CNIH3Protein cornichon homolog 3Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs).
RGMARepulsive guidance molecule AMember of the repulsive guidance molecule (RGM) family that performs several functions in the developing and adult nervous system.
GRIN2BGlutamate receptor ionotropic, NMDA 2BComponent of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+).
KRT8Keratin, type II cytoskeletal 8Required for the formation of KRT8/KRT18 filaments that are involved in ARHGEF40-mediated actin stress fiber formation and tensional force-induced stress fiber formation and reinforcement.
MAPK8Mitogen-activated protein kinase 8Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 8 · Druggable fraction: 0.27

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
Kinase25.0×0.173
Other/Unknown81.3×0.310
Enzyme (other)11.1×0.616

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
BMPR1BKinaseyes2.7.10.2TGFB_receptor, Activin_recp, Prot_kinase_dom
TACC2Other/UnknownnoTACC_C, TACC
AASSOther/UnknownnoSacchrp_dh_NADP-bd, AlaDH/PNT_NAD(H)-bd, AlaDH/PNT_N
LINC00474Other/Unknownno
FTOEnzyme (other)yes1.14.11.53FTO_C, FTO_cat_dom, FTO
CNIH3Other/UnknownnoCornichon, Cornichon_conserved
LINC00299Other/Unknownno
RGMAOther/UnknownnoRGM_C, RGM_N, RGM
GRIN2BOther/UnknownnoIontro_rcpt_C, Iono_Glu_rcpt_met, ANF_lig-bd_rcpt
KRT8Other/UnknownnoKeratin_II, IF_conserved, Keratin_2_head
MAPK8Kinaseyes2.7.11.24Prot_kinase_dom, MAP_kinase_CS, Ser/Thr_kinase_AS

Expression context

Cohort genes with no expression data: 0.

10 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)1
broad (>20)10
unknown0

Top tissues across cohort

TissueCohort genes
cortical plate4
bronchial epithelial cell2
gastrocnemius2
buccal mucosa cell2
adrenal tissue2
calcaneal tendon1
cauda epididymis1
apex of heart1
skeletal muscle tissue of biceps brachii1
left ovary1
mucosa of stomach1
right ovary1
male germ line stem cell (sensu Vertebrata) in testis1
placenta1
Brodmann (1909) area 101
endothelial cell1
primordial germ cell in gonad1
bone marrow cell1
granulocyte1
lower esophagus1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
BMPR1B239broadmarkercalcaneal tendon, bronchial epithelial cell, cauda epididymis
TACC2290ubiquitousmarkerapex of heart, skeletal muscle tissue of biceps brachii, gastrocnemius
AASS260ubiquitousmarkermucosa of stomach, left ovary, right ovary
LINC0047418tissue_specificyesmale germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell, placenta
FTO294ubiquitousmarkercortical plate, bronchial epithelial cell, Brodmann (1909) area 10
CNIH3204ubiquitousmarkerprimordial germ cell in gonad, cortical plate, endothelial cell
LINC00299157broadmarkergranulocyte, bone marrow cell, adrenal tissue
RGMA228broadmarkerlower esophagus, lower esophagus muscularis layer, gastrocnemius
GRIN2B138broadmarkerbuccal mucosa cell, cortical plate, Brodmann (1909) area 23
KRT8159ubiquitousmarkermucosa of transverse colon, endometrium epithelium, duodenum
MAPK8265ubiquitousmarkercortical plate, ganglionic eminence, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

SymbolInteractor count
MAPK85,984
KRT83,915
GRIN2B3,611
FTO2,496
TACC21,785
AASS1,333
CNIH31,072
RGMA763
BMPR1B116
LINC004740

Intra-cohort edges

ABSources
CNIH3RGMAstring_interaction

Structural data

PDB: 7 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
MAPK8P4598339
GRIN2BQ1322436
FTOQ9C0B128
AASSQ9UDR59
KRT8P057873
RGMAQ96B862
BMPR1BO002381

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
CNIH3Q8TBE185.15
LINC00474Q9P2X858.07
LINC00299Q6ZSB333.74
TACC2O95359

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 83. Enrichment computed across 11 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Killing mechanisms1713.8×0.058MAPK8
Activation of BMF and translocation to mitochondria1475.8×0.058MAPK8
Activation of BIM and translocation to mitochondria1356.9×0.058MAPK8
Interleukin-38 signaling1356.9×0.058MAPK8
Activated NTRK2 signals through FYN1237.9×0.065GRIN2B
Reversal of alkylation damage by DNA dioxygenases1203.9×0.065FTO
Activation of the AP-1 family of transcription factors1142.8×0.065MAPK8
Lysine catabolism1142.8×0.065AASS
WNT5:FZD7-mediated leishmania damping1119.0×0.065MAPK8
NRIF signals cell death from the nucleus189.2×0.065MAPK8
Developmental Lineage of Mammary Gland Alveolar Cells179.3×0.065KRT8
MECP2 regulates neuronal receptors and channels175.1×0.065GRIN2B
Ras activation upon Ca2+ influx through NMDA receptor171.4×0.065GRIN2B
Unblocking of NMDA receptors, glutamate binding and activation168.0×0.065GRIN2B
MAPK targets/ Nuclear events mediated by MAP kinases168.0×0.065MAPK8
Synaptic adhesion-like molecules168.0×0.065GRIN2B
Negative regulation of NMDA receptor-mediated neuronal transmission168.0×0.065GRIN2B
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1164.9×0.065MAPK8
Activation of BH3-only proteins162.1×0.065MAPK8
DNA Double Strand Break Response159.5×0.065MAPK8
Long-term potentiation159.5×0.065GRIN2B
Developmental Lineage of Mammary Gland Luminal Epithelial Cells157.1×0.065KRT8
Netrin-1 signaling154.9×0.065RGMA
Signaling by BMP144.6×0.071BMPR1B
FCERI mediated MAPK activation143.3×0.071MAPK8
Cargo concentration in the ER142.0×0.071CNIH3
MAP kinase activation138.6×0.071MAPK8
Intrinsic Pathway for Apoptosis136.6×0.071MAPK8
Fc epsilon receptor (FCERI) signaling134.0×0.071MAPK8
Interleukin-1 family signaling134.0×0.071MAPK8

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
JUN phosphorylation11872.4×0.014MAPK8
positive regulation of cell killing11872.4×0.014MAPK8
regulation of white fat cell proliferation11872.4×0.014FTO
obsolete L-lysine biosynthetic process via aminoadipic acid1936.2×0.014AASS
positive regulation of cyclase activity1624.1×0.014MAPK8
obsolete L-lysine catabolic process to acetyl-CoA via L-saccharopine1624.1×0.014AASS
RNA repair1624.1×0.014FTO
regulation of respiratory system process1624.1×0.014FTO
response to other organism1624.1×0.014KRT8
ovarian cumulus expansion1468.1×0.014BMPR1B
endochondral bone morphogenesis1468.1×0.014BMPR1B
regulation of brown fat cell differentiation1468.1×0.014FTO
negative regulation of chondrocyte proliferation1468.1×0.014BMPR1B
positive regulation of protein localization to mitochondrion1468.1×0.014MAPK8
synaptic transmission, glutamatergic279.7×0.014CNIH3, GRIN2B
BMP signaling pathway244.6×0.014BMPR1B, RGMA
MAPK cascade234.0×0.014BMPR1B, MAPK8
negative regulation of dendritic spine maintenance1312.1×0.019GRIN2B
obsolete lysine catabolic process1267.5×0.019AASS
regulation of lipid storage1267.5×0.019FTO
ovulation cycle1267.5×0.019BMPR1B
cell differentiation involved in embryonic placenta development1267.5×0.019KRT8
regulation of monoatomic cation transmembrane transport1234.1×0.021GRIN2B
regulation of AMPA receptor activity1187.2×0.024CNIH3
DNA alkylation repair1170.2×0.024FTO
negative regulation of collateral sprouting1170.2×0.024RGMA
negative regulation of axon regeneration1170.2×0.024RGMA
calcium ion transmembrane import into cytosol1170.2×0.024GRIN2B
positive regulation of extrinsic apoptotic signaling pathway via death domain receptors1156.0×0.025BMPR1B
ionotropic glutamate receptor signaling pathway1144.0×0.025GRIN2B

Therapeutics

Drugs indicated for this disease

2 approved, 13 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
BuprenorphineApproved (phase 4)
Levomethadyl AcetateApproved (phase 4)
DexmedetomidinePhase 3 (in late-stage trials)
DextromethorphanPhase 3 (in late-stage trials)
DiacetylmorphinePhase 3 (in late-stage trials)
GabapentinPhase 3 (in late-stage trials)
LofexidinePhase 3 (in late-stage trials)
MethadonePhase 3 (in late-stage trials)
MorphinePhase 3 (in late-stage trials)
NaloxonePhase 3 (in late-stage trials)
NaltrexonePhase 3 (in late-stage trials)
OpiumPhase 3 (in late-stage trials)
PregabalinPhase 3 (in late-stage trials)
RemifentanilPhase 3 (in late-stage trials)
TramadolPhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Atomoxetine, Cannabidiol, Cannabinol, Citalopram, Clonidine, Cocaine, Cycloserine, Dextroamphetamine, Disulfiram, Dronabinol, Hydrocortisone, Hydromorphone, Ibudilast, Isoflurane, Itraconazole, Lactose, Anhydrous, Lamotrigine, Levetiracetam, Lorcaserin, Mannitol, Memantine, Modafinil, Naloxegol, Nitric Oxide, Nitrous Oxide, Olanzapine, Oxycodone, Oxygen, Pioglitazone, Psilocybin, Sevoflurane, Suvorexant, Yohimbine.

Drug target analysis

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

Druggability breadth: 5 of 11 evidence-associated genes (45%) 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
BMPR1BMOMELOTINIB
FTOFLUORESCEIN
GRIN2BHALOPERIDOL
MAPK8MOMELOTINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
MAPK8504
GRIN2B354
BMPR1B284
FTO184
TACC200
AASS00
LINC0047400
CNIH300
LINC0029900
RGMA00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
MOMELOTINIB4BMPR1B, MAPK8
FEDRATINIB4BMPR1B, MAPK8
AXITINIB4BMPR1B, MAPK8
RUXOLITINIB4BMPR1B, MAPK8
VANDETANIB4BMPR1B
GILTERITINIB4BMPR1B, MAPK8
PAZOPANIB4BMPR1B, MAPK8
SUNITINIB4BMPR1B
DASATINIB4BMPR1B
QUIZARTINIB4BMPR1B
CRIZOTINIB4BMPR1B
FLUORESCEIN4FTO
DEMECLOCYCLINE4FTO
ROXADUSTAT4FTO
MECLOFENAMIC ACID4FTO
AMILORIDE4FTO
TACRINE4FTO, GRIN2B
ENTACAPONE4FTO
HALOPERIDOL4GRIN2B
DEXTROMETHORPHAN4GRIN2B
KETAMINE4GRIN2B
CYCLOSERINE4GRIN2B
MEMANTINE4GRIN2B
LEVORPHANOL4GRIN2B
AMANTADINE4GRIN2B
CHLORPROMAZINE4GRIN2B
PROCYCLIDINE4GRIN2B
ORPHENADRINE4GRIN2B
NERATINIB4MAPK8
PALBOCICLIB4MAPK8

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

SymbolAssaysType breakdown
MAPK81,116Binding:1104, Functional:9, ADMET:3
GRIN2B471Binding:429, Functional:36, ADMET:5, Toxicity:1
BMPR1B166Binding:164, ADMET:2
FTO153Binding:153

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
BMPR1B2.7.10.2non-specific protein-tyrosine kinase
FTO1.14.11.53mRNA N6-methyladenine demethylase
MAPK82.7.11.24mitogen-activated protein kinase

Cohort genes with high screening signal

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

SymbolChEMBL assays
BMPR1B166
FTO153
GRIN2B471
MAPK81,116

Pharmacogenomics

Cohort genes with a PharmGKB record: 11; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

28 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)
MOMELOTINIB4BMPR1B, MAPK8
FEDRATINIB4BMPR1B, MAPK8
AXITINIB4BMPR1B, MAPK8
RUXOLITINIB4BMPR1B, MAPK8
VANDETANIB4BMPR1B
GILTERITINIB4BMPR1B, MAPK8
PAZOPANIB4BMPR1B, MAPK8
SUNITINIB4BMPR1B
DASATINIB4BMPR1B
QUIZARTINIB4BMPR1B
CRIZOTINIB4BMPR1B
FLUORESCEIN4FTO
DEMECLOCYCLINE4FTO
ROXADUSTAT4FTO
MECLOFENAMIC ACID4FTO
AMILORIDE4FTO
TACRINE4FTO, GRIN2B
ENTACAPONE4FTO
HALOPERIDOL4GRIN2B
DEXTROMETHORPHAN4GRIN2B
CYCLOSERINE4GRIN2B
LEVORPHANOL4GRIN2B
AMANTADINE4GRIN2B
CHLORPROMAZINE4GRIN2B
PROCYCLIDINE4GRIN2B
ORPHENADRINE4GRIN2B
NERATINIB4MAPK8
PALBOCICLIB4MAPK8

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)4BMPR1B, FTO, GRIN2B, MAPK8
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug7TACC2, AASS, LINC00474, CNIH3, LINC00299, RGMA, KRT8

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
TACC20—
AASS0—
LINC004740—
CNIH30—
LINC002990—
RGMA0—
KRT80—

Clinical trials & evidence

Clinical trials

Clinical trials: 249.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified98
PHASE242
PHASE333
PHASE429
PHASE122
PHASE2/PHASE310
PHASE1/PHASE28
EARLY_PHASE17

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04811014PHASE4RECRUITINGYoung Houston Emergency Opioid Engagement System
NCT06574009PHASE4RECRUITINGBetter Options for Chronic Cancer Pain
NCT06949826PHASE4RECRUITINGBuprenorphine as a Post-operative Analgesic in Opioid-Naive Patients After Ankle Fracture Surgery
NCT00007527PHASE4COMPLETEDDetermine the Safety of a Sublingual Tablet Formulation of Buprenorphine and Naloxone by Extending the Combination Tablet Availability to Physicians in Office-Based Practice
NCT00015340PHASE4COMPLETEDBuprenorphine/Naloxone in the Treatment of Heroin Dependence - 14
NCT00241930PHASE4UNKNOWNIntegrating Buprenorphine Into HIV Treatment
NCT00263458PHASE4COMPLETEDIntegrating Buprenorphine Into the SFGH AIDS Program
NCT00300794PHASE4COMPLETEDEffects of Ketamine On Precipitated Opioid Withdrawal Under General Anaesthesia
NCT00367874PHASE4COMPLETEDTreatment of Polydrug-Using Opiate Dependents During Withdrawal
NCT00555425PHASE4COMPLETEDBuprenorphine Maintenance vs. Detoxification in Prescription Opioid Dependence
NCT00595764PHASE4COMPLETEDCounseling for Primary Care Office-based Buprenorphine
NCT00604188PHASE4COMPLETEDA Randomized Acceptability and Safety Study of Suboxone Induction in Heroin Users (P05042)(COMPLETED)
NCT00605033PHASE4COMPLETEDA Randomized Acceptability and Safety Study of the Transfer From Subutex to Suboxone in Opioid- Dependent Subjects (Study P04843)(COMPLETED)
NCT00684073PHASE4COMPLETEDPreference for Subutex® (Buprenorphine) Versus Suboxone® (Buprenorphine/Naloxone) in Opioid Dependent Patients on Subutex® (Study P05094)(COMPLETED)
NCT00763958PHASE4COMPLETEDRelapse Prevention to Reduce HIV Among Women Prisoners
NCT00901875PHASE4COMPLETEDMulticentre Trial of Suboxone in Opiate-dependent Subjects in Taiwan
NCT01453374PHASE4COMPLETEDA Study of VIVITROL in the Prevention of Re-arrest and Re-incarceration
NCT01841931PHASE4TERMINATEDBuprenorphine Treatment: A Safe Alternative for Opioid Dependent Pain Patients
NCT02038790PHASE4COMPLETEDUsability of Zubsolv Sublingual Tablets 5.7/1.4 to Suboxone Sublingual Film 8/2 In Buprenorphine/Naloxone Treated Opioid Dependent Population
NCT02200406PHASE4COMPLETEDDesvenlafaxine in Opioid-Dependent Patients
NCT02324725PHASE4COMPLETEDBiomarkers of Injectable Extended Release Naltrexone Treatment
NCT03235154PHASE4COMPLETEDA Pilot Study of Treating HCV at a Psychiatrist-staffed Outpatient Addiction Clinic
NCT03305666PHASE4COMPLETEDTrial of Injected Liposomal Bupivacaine vs Bupivacaine Infusion After Surgical Stabilization of Rib Fractures
NCT03334903PHASE4COMPLETEDGabapentin Regimens and Their Effects on Opioid Consumption
NCT03534102PHASE4WITHDRAWNCan Simplified and More Detailed Instructions Affect Post-Operative Narcotic Consumption
NCT03549312PHASE4UNKNOWNSwitch to Genvoya Followed by HCV Therapy With Epclusa Followed by Simplification of HIV Therapy With Biktarvy in Patients With HIV-HCV Co-Infected Subjects on Opioid Substitution Therapy
NCT03604159PHASE4COMPLETEDXRB vs. SLB in Jail and at Re-entry: Pilot, Proof of Concept
NCT04033562PHASE4TERMINATEDThe Analgesic Efficacy of Continuous Sub-fascial Bupivacaine Infusion and Lidocaine Patches in Post-cesarean Patients With Opiate Use Disorder: A Comparative Efficacy Analysis
NCT05644587PHASE4TERMINATEDNovel Induction to Buprenorphine/Naloxone
NCT03345173PHASE3ACTIVE_NOT_RECRUITINGFacilitating Rapid Naltrexone Initiation
NCT00147784PHASE3COMPLETEDHEPMET-1: Evaluate the Feasibility, Mental Sideeffects and the Efficacy of Hepatitis C Treatment in a MMT Group.
NCT00156936PHASE3TERMINATEDALK21-006EXT: Long-term Safety of Medisorb® Naltrexone (VIVITROL®) in Alcohol- or Opioid-dependent Adults (Extension of Study ALK21-006 [NCT01218997])
NCT00268814PHASE3COMPLETEDThe German Project of Heroin Assisted Treatment of Opiate Dependent Patients
NCT00271219PHASE3COMPLETEDRCT Comparing Methadone and Buprenorphine in Pregnant Women
NCT00316277PHASE3COMPLETEDPrescription Opioid Addiction Treatment Study (POATS)
NCT00351026PHASE3COMPLETEDMethadone Maintenance & HIV Risk in Ukraine
NCT00447564PHASE3COMPLETEDSafety and Efficacy of Probuphine in the Treatment of Opioid Dependence
NCT00475878PHASE3COMPLETEDSSRI and Buprenorphine
NCT00476242PHASE2/PHASE3COMPLETEDMemantine as a Supplement to Naltrexone in Treating Heroin Dependence
NCT00521157PHASE2/PHASE3COMPLETEDNaltrexone Implants as an Aid in Preventing Relapse Following Inpatient Treatment for Opioid Addiction

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
BUPRENORPHINE418
NALTREXONE413
NALOXONE410
LOFEXIDINE48
METHADONE47
CITALOPRAM43
DESVENLAFAXINE43
FLUPHENAZINE DECANOATE43
HYDROMORPHONE43
LEVOMETHADYL ACETATE43
ZIPRASIDONE43
ATOMOXETINE42
CLONIDINE42
DISULFIRAM42
MEMANTINE42
TIAGABINE42
VALPROIC ACID42
COCAINE41
DEXTROAMPHETAMINE41
DRONABINOL41
GABAPENTIN41
IBUDILAST41
ISRADIPINE41
KETAMINE41
LACOSAMIDE41
LORCASERIN41
MANNITOL41
MODAFINIL41
MORPHINE41
RIFAPENTINE41

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 71

This page pulls from 71 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncicd10cmintactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot