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Atlas / Disease / Pathological gambling

Pathological gambling

disease
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Also known as compulsive gambling

Summary

Pathological gambling (MONDO:0011662) is a disease with 3 cohort genes (3 GWAS associations across 1 studies) and 41 clinical trials. Top therapeutic interventions include naltrexone, naloxone, and tolcapone.

At a glance

  • Cohort genes: 3
  • GWAS associations: 3
  • Clinical trials: 41

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namepathological gambling
Mondo IDMONDO:0011662
EFOEFO:1001926
MeSHD005715
OMIM606349
DOIDDOID:12399
ICD-10-CMF63.0
NCITC94335
SNOMED CT18085000
UMLSC0030662
MedGen14632
Is cancer (heuristic)no

Also known as: compulsive gambling · pathological gambling

Data availability: 3 GWAS associations (1 study).

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › impulse control disorder › pathological gambling

Related subtypes (6): kleptomania, intermittent explosive disorder, pyromania, Kluver-Bucy syndrome, trichotillomania, primary polydipsia

Genetics & variants

GWAS landscape

3 GWAS associations across 1 studies. Top hits map to 3 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs60659041e-06PLTP?1.89
rs75913516e-06PRKCET1.67
rs39434187e-06XYLT1A1.71

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST003648Lang M20164450Genome-wide association study of pathological gambling.

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/intergenic3

MAF distribution

BucketVariants
common (>=0.05)3
low_freq (0.01-0.05)0
rare (<0.01)0
unknown0

Functional consequences

ConsequenceCount
intron_variant3

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs60659042045906012G>A0.05intron_variantPLTP1e-06Tier 4: intronic/intergenic
rs7591351245836267C>G,T0.05intron_variantPRKCE6e-06Tier 4: intronic/intergenic
rs39434181617243867A>C,G,T0.05intron_variantXYLT17e-06Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
XYLT1Orphanet:1425Desbuquois syndrome
XYLT1Orphanet:370930XYLT1-CDG

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only3

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
XYLT1HGNC:15516ENSG00000103489Q86Y38Xylosyltransferase 1gwas
PLTPHGNC:9093ENSG00000100979P55058Phospholipid transfer proteingwas
PRKCEHGNC:9401ENSG00000171132Q02156Protein kinase C epsilon typegwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
XYLT1Xylosyltransferase 1Catalyzes the first step in the biosynthesis of chondroitin sulfate and dermatan sulfate proteoglycans, such as DCN.
PLTPPhospholipid transfer proteinMediates the transfer of phospholipids and free cholesterol from triglyceride-rich lipoproteins (low density lipoproteins or LDL and very low density lipoproteins or VLDL) into high-density lipoproteins (HDL) as well as the exchange of pho…
PRKCEProtein kinase C epsilon typeCalcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motil…

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

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
Kinase19.2×0.313
Enzyme (other)14.0×0.345
Other/Unknown10.6×0.914

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
XYLT1Enzyme (other)yes2.4.2.26Glyco_trans_14, XylT_C, XYLT
PLTPOther/UnknownnoLipid-bd_serum_glycop_C, Lipid-bd_serum_glycop_N, Bactericidal_perm-incr_a/b_dom
PRKCEKinaseyes2.7.11.13C2_dom, Prot_kinase_dom, AGC-kinase_C

Expression context

Cohort genes with no expression data: 0.

3 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)3
unknown0

Top tissues across cohort

TissueCohort genes
cartilage tissue1
hair follicle1
tibia1
mucosa of stomach1
right adrenal gland cortex1
right coronary artery1
buccal mucosa cell1
lateral nuclear group of thalamus1
sural nerve1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
XYLT1272broadmarkertibia, cartilage tissue, hair follicle
PLTP276ubiquitousmarkerright coronary artery, right adrenal gland cortex, mucosa of stomach
PRKCE233ubiquitousmarkerbuccal mucosa cell, sural nerve, lateral nuclear group of thalamus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
PRKCE2,158
PLTP1,417
XYLT1704

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
XYLT1Q86Y389
PRKCEQ021562

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
PLTPP5505889.36

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
HDL remodeling1380.7×0.024PLTP
SHC1 events in ERBB2 signaling1158.6×0.024PRKCE
Effects of PIP2 hydrolysis1152.3×0.024PRKCE
Role of phospholipids in phagocytosis1152.3×0.024PRKCE
Glycosaminoglycan-protein linkage region biosynthesis1131.3×0.024XYLT1
Signaling by ERBB21115.3×0.024PRKCE
DAG and IP3 signaling1105.7×0.024PRKCE
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux1102.9×0.024PLTP
Fcgamma receptor (FCGR) dependent phagocytosis192.8×0.024PRKCE
G alpha (z) signalling events177.7×0.026PRKCE
Platelet activation, signaling and aggregation135.2×0.051PRKCE
Intracellular signaling by second messengers130.4×0.054PRKCE
G alpha (q) signalling events119.1×0.079PRKCE
Signaling by Receptor Tyrosine Kinases117.2×0.081PRKCE
GPCR downstream signalling114.5×0.090PRKCE
Signaling by GPCR113.4×0.091PRKCE
Hemostasis112.0×0.095PRKCE
Innate Immune System18.5×0.126PRKCE
Immune System14.3×0.225PRKCE
Signal Transduction13.4×0.267PRKCE

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
toxin catabolic process15617.3×0.005PRKCE
vitamin E biosynthetic process15617.3×0.005PLTP
TRAM-dependent toll-like receptor 4 signaling pathway11872.4×0.007PRKCE
glycolipid transport11872.4×0.007PLTP
glycosaminoglycan-protein linkage region biosynthetic process11404.3×0.008XYLT1
positive regulation of mucus secretion11123.5×0.008PRKCE
negative regulation of sodium ion transmembrane transport1936.2×0.009PRKCE
positive regulation of lipid catabolic process1624.1×0.009PRKCE
ceramide transport1510.7×0.009PLTP
ossification involved in bone maturation1468.1×0.009XYLT1
mucus secretion1432.1×0.009PRKCE
response to morphine1401.2×0.009PRKCE
macrophage activation involved in immune response1374.5×0.009PRKCE
positive regulation of fibroblast migration1374.5×0.009PRKCE
cellular response to ethanol1351.1×0.009PRKCE
positive regulation of synaptic transmission, GABAergic1330.4×0.009PRKCE
locomotory exploration behavior1330.4×0.009PRKCE
regulation of release of sequestered calcium ion into cytosol1312.1×0.009PRKCE
regulation of insulin secretion involved in cellular response to glucose stimulus1312.1×0.009PRKCE
positive regulation of superoxide anion generation1295.6×0.009PRKCE
glycosaminoglycan biosynthetic process1280.9×0.009XYLT1
proteoglycan biosynthetic process1280.9×0.009XYLT1
cellular response to prostaglandin E stimulus1280.9×0.009PRKCE
high-density lipoprotein particle remodeling1267.5×0.009PLTP
cell-substrate adhesion1255.3×0.009PRKCE
phospholipid transport1234.1×0.009PLTP
Fc-gamma receptor signaling pathway involved in phagocytosis1234.1×0.009PRKCE
positive regulation of cholesterol efflux1208.1×0.009PLTP
chondroitin sulfate proteoglycan biosynthetic process1208.1×0.009XYLT1
heparan sulfate proteoglycan biosynthetic process1187.2×0.010XYLT1

Therapeutics

Drugs indicated for this disease

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

DrugDevelopment status
NaltrexonePhase 3 (in late-stage trials)
OlanzapinePhase 3 (in late-stage trials)
TopiramatePhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Ecopipam, Milk Thistle, Nalmefene, Tolcapone.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
PRKCEINGENOL MEBUTATE

Top cohort targets by molecule count

SymbolMoleculesMax phase
PRKCE214
XYLT100
PLTP00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
INGENOL MEBUTATE4PRKCE
MIDOSTAURIN4PRKCE
TAMOXIFEN4PRKCE
FEDRATINIB4PRKCE
RUXOLITINIB4PRKCE
BOSUTINIB4PRKCE
SURAMIN3PRKCE
FASUDIL3PRKCE
ALVOCIDIB3PRKCE
CURCUMIN3PRKCE
ENZASTAURIN HYDROCHLORIDE3PRKCE
ENZASTAURIN3PRKCE
LESTAURTINIB3PRKCE
RUBOXISTAURIN3PRKCE
PHORBOL MYRISTATE ACETATE2PRKCE
EDELFOSINE2PRKCE
UPROSERTIB2PRKCE
UCN-012PRKCE
DAROVASERTIB2PRKCE
SOTRASTAURIN2PRKCE
GSK-6906931PRKCE

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

SymbolAssaysType breakdown
PRKCE722Binding:707, Functional:14, ADMET:1
PLTP10Binding:10

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
XYLT12.4.2.26protein xylosyltransferase
PRKCE2.7.11.13protein kinase C

Cohort genes with high screening signal

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

SymbolChEMBL assays
PRKCE722

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

21 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)
INGENOL MEBUTATE4PRKCE
MIDOSTAURIN4PRKCE
TAMOXIFEN4PRKCE
FEDRATINIB4PRKCE
RUXOLITINIB4PRKCE
BOSUTINIB4PRKCE
SURAMIN3PRKCE
FASUDIL3PRKCE
ALVOCIDIB3PRKCE
CURCUMIN3PRKCE
ENZASTAURIN HYDROCHLORIDE3PRKCE
ENZASTAURIN3PRKCE
LESTAURTINIB3PRKCE
RUBOXISTAURIN3PRKCE
PHORBOL MYRISTATE ACETATE2PRKCE
EDELFOSINE2PRKCE
UPROSERTIB2PRKCE
UCN-012PRKCE
DAROVASERTIB2PRKCE
SOTRASTAURIN2PRKCE
GSK-6906931PRKCE

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1PRKCE
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug1XYLT1
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1PLTP

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
XYLT10—
PLTP10—

Clinical trials & evidence

Clinical trials

Clinical trials: 41.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified22
PHASE211
PHASE33
PHASE42
PHASE12
PHASE2/PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00571103PHASE4COMPLETEDAcamprosate in the Treatment of Pathological Gambling
NCT01528007PHASE4COMPLETEDTreatment of Pathological Gambling With Naltrexone Pharmacotherapy and Brief Intervention
NCT00132119PHASE2/PHASE3COMPLETEDNalmefene Gambling Study: Study of Nalmefene HCl in the Treatment of Pathological Gambling
NCT00203645PHASE3COMPLETEDMinimal and Brief Treatments for Pathological Gamblers
NCT00245583PHASE3TERMINATEDTopiramate in the Treatment of Pathological Gambling
NCT00438776PHASE3COMPLETEDSafety and Efficacy Trial of Olanzapine in Outpatients With Pathological Gambling
NCT00078273PHASE2COMPLETEDIndicated Prevention With At-Risk Gamblers
NCT00337753PHASE2COMPLETEDCognitive Behavioral Therapy for Pathological Gambling
NCT00585169PHASE2COMPLETEDMemantine Treatment Study of Pathological Gambling
NCT00927563PHASE2COMPLETEDTolcapone Treatment of Pathological Gambling
NCT01057862PHASE2COMPLETEDInvestigation of Naltrexone for Pathological Gambling
NCT01215357PHASE2COMPLETEDClinical Study to Determine if Ecopipam Can Reduce Urges to Gamble
NCT01340274PHASE2WITHDRAWNCommunity Reinforcement Approach and Family Training (CRAFT) for Problem Gambling
NCT01843699PHASE2COMPLETEDTopiramate Trial for Pathological Gamblers
NCT02203786PHASE2COMPLETEDD1 and D2 Dopamine Receptors in Gambling and Amphetamine Reinforcement
NCT02337634PHASE2COMPLETEDMilk Thistle in Pathological Gambling
NCT03430180PHASE2UNKNOWNEffects of Intranasal Naloxone on Gambling Urges and Craving in Gambling Disorder
NCT00273702PHASE1COMPLETEDAn Open-Label Study of N-Acetyl Cysteine in Pathological Gambling
NCT01154712PHASE1UNKNOWNDeep Low-Frequency Repetitive Transcranial Magnetic Stimulation for Cessation of Pathological Gambling
NCT06642155Not specifiedNOT_YET_RECRUITINGTheory-based Intervention for Promoting Responsible Gambling Among College Students
NCT00055393Not specifiedCOMPLETEDBupropion in the Treatment of Pathological Gambling
NCT00211822Not specifiedTERMINATEDFunctional Magnetic Resonance Imaging (fMRI) Studies in Pathological Gambling (PG) and Obsessive-Compulsive Disorder (OCD)
NCT00360321Not specifiedUNKNOWNDescriptive Study of a French Sample of at Risk and Pathological Gamblers Followed in a French Structure Specialised in Addictive Disorders.
NCT00580567Not specifiedCOMPLETEDImpulsivity in Pathological Gambling
NCT00685724Not specifiedCOMPLETEDA Pilot SMART Design for Pathological Gamblers
NCT01135264Not specifiedCOMPLETEDCognitive-Motivational Behavior Therapy for Pathological Gamblers
NCT01381250Not specifiedCOMPLETEDEffects of Internet-based Treatment of Pathological Gambling
NCT01528982Not specifiedCOMPLETEDSusceptibility to Pathological Gambling
NCT01560351Not specifiedTERMINATEDRepeated Low-frequency Transcranial Magnetic Stimulation Reduces Cue-induced Craving: a Randomized, Prospective, Double-blind, Sham-controlled, Cross-over Study
NCT01596478Not specifiedUNKNOWNEffectiveness of Therapy Treatment
NCT01743092Not specifiedCOMPLETEDTesting Resources: Manual and Webinar Guided Treatment vs. Manual Guided Treatment
NCT02240485Not specifiedCOMPLETEDIntegrative Couple Treatment for Pathological Gambling
NCT02491996Not specifiedUNKNOWNThe Efficacy of Therapy Focused on Desire-satisfaction for Disordered Gamblers
NCT02590211Not specifiedCOMPLETEDPoker, Skills and Associated Problems
NCT02772978Not specifiedCOMPLETEDDopamine Responsivity in Gamblers
NCT03464838Not specifiedUNKNOWNEffects of Transcranial Direct Current Stimulation (tDCS) in Gambling Disorder
NCT03673800Not specifiedUNKNOWNCognitive Control Training in Online Problem Gambling
NCT04074681Not specifiedUNKNOWNEfficacy of an Internet-based Psychological Intervention for Problem Gambling and Gambling Disorder
NCT04842461Not specifiedCOMPLETEDMental Health, Addictions and Biomarkers in High Athletes Performance
NCT05051085Not specifiedCOMPLETEDFeasibility of the Internet-delivered Treatment SpilleFri for Patients With Pathological Gambling

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
NALTREXONE44
NALOXONE43
TOLCAPONE42
ACAMPROSATE41
DEXTROAMPHETAMINE SULFATE41
FLUPHENAZINE41
HALOPERIDOL41
MEMANTINE41
NALMEFENE HYDROCHLORIDE41
TOPIRAMATE41
ECOPIPAM31
MILK THISTLE31

About this page

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

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This page pulls from 71 datasets indexed by BioBTree:

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