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Postherpetic neuralgia

disease
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Summary

Postherpetic neuralgia (MONDO:0041052) is a disease with 3 cohort genes (5 GWAS associations across 1 studies) and 96 clinical trials. Top therapeutic interventions include pregabalin, capsaicin, and lidocaine.

At a glance

  • Cohort genes: 3
  • GWAS associations: 5
  • Clinical trials: 96

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namepostherpetic neuralgia
Mondo IDMONDO:0041052
Orphanet466673
ICD-111797210650
SNOMED CT2177002
UMLSC0032768
MedGen18589
GARD0027961
Is cancer (heuristic)no

Also known as: postherpetic neuralgia

Data availability: 5 GWAS associations (1 study).

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › peripheral nervous system disorder › peripheral neuropathy › neuralgia › post-infectious neuralgia › postherpetic neuralgia

Genetics & variants

GWAS landscape

5 GWAS associations across 1 studies. Top hits map to 4 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs47738402e-07ABCC4?
rs101145083e-06RN7SL100P - PLAA?
rs124585236e-06TMEM241, CABLES1?
rs21671516e-06NRXN3?
rs108510146e-06LINC02460 - RPL17P37?

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST012124Nishizawa D2021890Genome-wide association study identifies candidate loci associated with chronic pain and postherpetic neuralgia.

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/intergenic5

MAF distribution

BucketVariants
common (>=0.05)5
low_freq (0.01-0.05)0
rare (<0.01)0
unknown0

Functional consequences

ConsequenceCount
intron_variant3
intergenic_variant2

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs47738401395118171G>A0.05intron_variantABCC42e-07Tier 4: intronic/intergenic
rs10114508926902595T>A,C,G0.05intergenic_variantRN7SL100P - PLAA3e-06Tier 4: intronic/intergenic
rs124585231823240764A>C,G0.05intron_variantTMEM241, CABLES16e-06Tier 4: intronic/intergenic
rs21671511479396990T>C0.05intron_variantNRXN36e-06Tier 4: intronic/intergenic
rs1085101412118692412T>C0.05intergenic_variantLINC02460 - RPL17P376e-06Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only3

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
CABLES1HGNC:25097ENSG00000134508Q8TDN4CDK5 and ABL1 enzyme substrate 1gwas
ABCC4HGNC:55ENSG00000125257O15439ATP-binding cassette sub-family C member 4gwas
NRXN3HGNC:8010ENSG00000021645Q9HDB5Neurexin-3-betagwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
CABLES1CDK5 and ABL1 enzyme substrate 1Cyclin-dependent kinase binding protein.
ABCC4ATP-binding cassette sub-family C member 4ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells.
NRXN3Neurexin-3-betaNeuronal cell surface protein that may be involved in cell recognition and cell adhesion.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Transporter125.9×0.076
Other/Unknown21.2×0.587

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
CABLES1Other/UnknownnoCyclin_N, CABLES1/2, Cyclin-like_sf
ABCC4Transporteryes7.6.2.2ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom
NRXN3Other/UnknownnoLaminin_G, Neurexin-like, ConA-like_dom_sf

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
caudate nucleus1
nucleus accumbens1
putamen1
buccal mucosa cell1
palpebral conjunctiva1
secondary oocyte1
cerebellar vermis1
substantia nigra pars compacta1
substantia nigra pars reticulata1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
CABLES1218ubiquitousmarkerputamen, caudate nucleus, nucleus accumbens
ABCC4230ubiquitousmarkerpalpebral conjunctiva, secondary oocyte, buccal mucosa cell
NRXN3231ubiquitousmarkercerebellar vermis, substantia nigra pars compacta, substantia nigra pars reticulata

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
ABCC42,497
CABLES1753
NRXN3165

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
ABCC4O1543925

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
NRXN3Q9HDB559.75
CABLES1Q8TDN457.66

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. 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
Azathioprine ADME1165.5×0.030ABCC4
Paracetamol ADME1141.0×0.030ABCC4
Cyclin E associated events during G1/S transition195.2×0.030CABLES1
Cyclin A:Cdk2-associated events at S phase entry188.5×0.030CABLES1
G1/S Transition177.7×0.030CABLES1
Drug ADME176.1×0.030ABCC4
Neurexins and neuroligins165.6×0.030NRXN3
Mitotic G1 phase and G1/S transition161.4×0.030CABLES1
S Phase160.4×0.030CABLES1
Hemostasis224.0×0.030CABLES1, ABCC4
Response to elevated platelet cytosolic Ca2+154.4×0.030ABCC4
ABC-family protein mediated transport140.5×0.037ABCC4
Platelet activation, signaling and aggregation135.2×0.039ABCC4
Platelet degranulation129.3×0.043ABCC4
Factors involved in megakaryocyte development and platelet production122.1×0.053CABLES1
Cell Cycle, Mitotic116.1×0.069CABLES1
Cell Cycle112.0×0.086CABLES1
Transport of small molecules18.4×0.115ABCC4

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
kynurenic acid metabolic process15617.3×0.005ABCC4
cAMP transport12808.7×0.005ABCC4
obsolete L-tryptophan metabolic process11872.4×0.005ABCC4
platelet degranulation11123.5×0.005ABCC4
prostaglandin secretion11123.5×0.005ABCC4
urate transport1802.5×0.005ABCC4
leukotriene transport1802.5×0.005ABCC4
prostaglandin transport1624.1×0.005ABCC4
export across plasma membrane1561.7×0.005ABCC4
neuron cell-cell adhesion1330.4×0.007NRXN3
xenobiotic transmembrane transport1312.1×0.007ABCC4
vocalization behavior1295.6×0.007NRXN3
bile acid and bile salt transport1216.1×0.009ABCC4
adult behavior1156.0×0.012NRXN3
learning193.6×0.018NRXN3
social behavior190.6×0.018NRXN3
transport across blood-brain barrier159.8×0.025ABCC4
transmembrane transport156.2×0.026ABCC4
xenobiotic metabolic process149.7×0.027ABCC4
axon guidance130.2×0.043NRXN3
regulation of cell cycle124.9×0.048CABLES1
cilium assembly124.5×0.048ABCC4
angiogenesis120.8×0.053NRXN3
cell division115.4×0.066CABLES1
nervous system development115.3×0.066CABLES1
signal transduction15.3×0.176NRXN3

Therapeutics

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
ABCC4CEFOTAXIME SODIUM

Top cohort targets by molecule count

SymbolMoleculesMax phase
ABCC41024
CABLES100
NRXN300

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
CEFOTAXIME SODIUM4ABCC4
TELMISARTAN4ABCC4
OXAPROZIN4ABCC4
CEFUROXIME AXETIL4ABCC4
AMLEXANOX4ABCC4
VALRUBICIN4ABCC4
RIMONABANT4ABCC4
ACITRETIN4ABCC4
TELITHROMYCIN4ABCC4
SAQUINAVIR4ABCC4
FEBUXOSTAT4ABCC4
CEFAZOLIN SODIUM4ABCC4
DOXAZOSIN MESYLATE4ABCC4
GEMIFLOXACIN MESYLATE4ABCC4
OLMESARTAN MEDOXOMIL4ABCC4
TRAVOPROST4ABCC4
DINOPROST TROMETHAMINE4ABCC4
KETOROLAC TROMETHAMINE4ABCC4
TEMSIROLIMUS4ABCC4
ROSIGLITAZONE4ABCC4
REPAGLINIDE4ABCC4
CLOFAZIMINE4ABCC4
QUINIDINE4ABCC4
CARPROFEN4ABCC4
TOLCAPONE4ABCC4
BUDESONIDE4ABCC4
MYCOPHENOLATE MOFETIL4ABCC4
GLIMEPIRIDE4ABCC4
NICARDIPINE4ABCC4
DROSPIRENONE4ABCC4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

SymbolAssaysType breakdown
ABCC497Functional:71, ADMET:21, Binding:5
CABLES11Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
ABCC47.6.2.2, 7.6.2.3ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter

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

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)
CEFOTAXIME SODIUM4ABCC4
TELMISARTAN4ABCC4
OXAPROZIN4ABCC4
CEFUROXIME AXETIL4ABCC4
AMLEXANOX4ABCC4
VALRUBICIN4ABCC4
RIMONABANT4ABCC4
ACITRETIN4ABCC4
TELITHROMYCIN4ABCC4
SAQUINAVIR4ABCC4
FEBUXOSTAT4ABCC4
CEFAZOLIN SODIUM4ABCC4
DOXAZOSIN MESYLATE4ABCC4
GEMIFLOXACIN MESYLATE4ABCC4
OLMESARTAN MEDOXOMIL4ABCC4
TRAVOPROST4ABCC4
DINOPROST TROMETHAMINE4ABCC4
KETOROLAC TROMETHAMINE4ABCC4
TEMSIROLIMUS4ABCC4
ROSIGLITAZONE4ABCC4
REPAGLINIDE4ABCC4
CLOFAZIMINE4ABCC4
QUINIDINE4ABCC4
CARPROFEN4ABCC4
TOLCAPONE4ABCC4
BUDESONIDE4ABCC4
MYCOPHENOLATE MOFETIL4ABCC4
GLIMEPIRIDE4ABCC4
NICARDIPINE4ABCC4
DROSPIRENONE4ABCC4

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1ABCC4
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug2CABLES1, NRXN3

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
CABLES11—
NRXN30—

Clinical trials & evidence

Clinical trials

Clinical trials: 96.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified37
PHASE235
PHASE413
PHASE36
PHASE14
PHASE1/PHASE21

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00407511PHASE4COMPLETEDPregabalin Treatment Of Peripheral Neuropathic Pain Associated With Diabetic Peripheral NeP (DPN), Postherpetic Neuralgia (PHN), HIV-related NeP (HIV), and Chemotherapy Induced NeP
NCT00527202PHASE4COMPLETEDEfficacy Study of Botox to Treat Neuropathic Pain
NCT00885586PHASE4COMPLETEDAcupuncture in Herpes Zoster Neuralgia (ACUZoster)
NCT00904020PHASE4COMPLETEDA Study of the Effectiveness And Safety Of Lidoderm® As Add-On Treatment in Patients With Postherpetic Neuralgia, Diabetic Neuropathy, or Low Back Pain
NCT00904202PHASE4COMPLETEDA Study Of Lidocaine Patch 5% Alone, Gabapentin Alone, And Lidocaine Patch 5% And Gabapentin In Combination For The Relief Of Pain In Patients With Diverse Peripheral Neuropathic Pain Conditions
NCT01116531PHASE4WITHDRAWNEfficacy, Safety, Tolerability and Pharmacokinetics of Concomitant Administration of Tramadol With Duloxetine or Pregabalin
NCT01251211PHASE4COMPLETEDBotulinum Toxin in Peripheral Neuropathic Pain
NCT01264237PHASE4UNKNOWNEvaluation of the Efficacy, Tolerability and Safety of Etoricoxib (Arcoxia) in Patients With Neuropathic Pain
NCT01302275PHASE4COMPLETEDOxcarbazepine for the Treatment of Chronic Peripheral Neuropathic Pain
NCT01455428PHASE4COMPLETEDPregabalin for Treatment of Patients With Postherpetic Neuralgia (PHN)
NCT01603394PHASE4TERMINATEDPilot Study Of Pregabalin And Prediction Of Treatment Response In Patients With Postherpetic Neuralgia
NCT01713426PHASE4COMPLETEDA Study to Compare QUTENZA With Pregabalin for the Treatment of Peripheral Neuropathic Pain (PNP) After 8 Weeks of Treatment
NCT04664530PHASE4UNKNOWNThe Study on the Esketamine in the Treatment of Postherpetic Neuralgia
NCT00007501PHASE3COMPLETEDShingles Prevention Study
NCT01008553PHASE3COMPLETEDA Confirmatory Study of Fentanyl in Participants With Post-herpetic Neuralgia, Complex Regional Pain Syndrome or Postoperative Pain Syndrome
NCT02412917PHASE3TERMINATEDA Comparative Study of FV-100 vs. Valacyclovir for the Prevention of Post-Herpetic Neuralgia
NCT02868801PHASE3UNKNOWNEfficacy and Safety of Pregabalin Sustained Release Tablet for Postherpetic Neuralgia
NCT05140863PHASE3COMPLETEDTo Evaluate the Efficacy and Safety of HSK16149 Capsule in Chinese Patients With Postherpetic Neuralgia
NCT07349680PHASE3COMPLETEDUltrasound-Guided Thoracic Paravertebral Block With Steroid and Local Anesthetic for Acute Herpes Zoster: Effects on Pain Control and Prevention of Postherpetic Neuralgia
NCT06708416PHASE2ACTIVE_NOT_RECRUITINGA Study of ONO-1110 in Patients With Postherpetic Neuralgia
NCT07275762PHASE2RECRUITINGY-4 to Treat the Postherpetic Neuralgia
NCT00168441PHASE2COMPLETEDA Study Evaluating Botulinum Toxin Type A in Subjects With Postherpetic Neuralgia
NCT00238511PHASE2COMPLETEDAn Open-Label Follow-on Trial to Assess the Long-Term Safety and Efficacy of Oral SPM 927 in Subjects With Postherpetic Neuralgia (PHN)
NCT00352651PHASE2TERMINATEDStudy to Find Out if Therapy With the Drug Pregabalin Relieves Pain During Shingles Compared With Placebo
NCT00478179PHASE2COMPLETEDStudy of a Bupivacaine Patch (Eladur™) to Treat Post- Herpetic Neuralgia
NCT00492323PHASE2COMPLETEDAn Effectiveness and Safety Study With RWJ-333369 (Carisbamate) for the Study of Postherpetic Neuralgia (PHN).
NCT00506610PHASE2WITHDRAWNA Study to Determine if an Investigational Pain Medicine Provides Relief of Chronic Pain After a Shingles Outbreak
NCT00576108PHASE2COMPLETEDA 2 Week Study of Topical KD7040 in the Treatment of Postherpetic Neuralgia (PHN)
NCT00599638PHASE2COMPLETEDA Study To Compare Pregabalin/PF-00489791 Combination Versus Pregabalin Alone In Post-Herpetic Neuralgia
NCT00609323PHASE2COMPLETEDLidocaine and Tetracaine Cream to Treat Postherpetic Neuralgia (PHN)
NCT00612105PHASE2COMPLETEDSafety/Efficacy Study of Retigabine vs. Placebo in Post-Herpetic Neuralgia (PHN)
NCT00652184PHASE2UNKNOWNStudy to Compare Efficacy of Topical ARYS-01 (Sorivudine) Cream 3%, Oral Valaciclovir and Combination ARYS-01 Cream 3%/Oral Valaciclovir for Treatment of Herpes Zoster (Shingles)
NCT00809679PHASE2TERMINATEDAnalgesic Efficacy and Safety Study of T-62 in Subjects With Postherpetic Neuralgia
NCT00813826PHASE2UNKNOWNEfficacy and Safety Study of SLC022 in Treating Pain Associated With Post Herpetic Neuralgia
NCT00845923PHASE2COMPLETEDEvaluation of Civamide Patch in Treatment of Postherpetic Neuralgia and Post-Incisional Neuralgia
NCT00861068PHASE2COMPLETEDA Multi-Centre, Randomized, Double-Blind, Placebo Controlled Pilot Trial to Assess the Efficacy, Safety, and Tolerability of SPM 927 in Subjects With Postherpetic Neuralgia (PHN).
NCT00916942PHASE2COMPLETEDStudy of NGX-4010 With the Use of Open Label Lidocaine (2.5%)/Prilocaine (2.5%) Cream for the Treatment of Postherpetic Neuralgia (PHN)
NCT00981227PHASE2COMPLETEDEfficacy and Safety of Eslicarbazepine Acetate as Therapy for Patients With Post-Herpetic Neuralgia
NCT01058642PHASE2TERMINATEDStudy to Assess the Efficacy, Safety, and Tolerability of ADL5747 in Participants With Postherpetic Neuralgia
NCT01088256PHASE2TERMINATEDEfficacy of Etoricoxib on Peripheral Hyperalgesia

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
PREGABALIN411
CAPSAICIN43
LIDOCAINE43
VALACYCLOVIR43
ETORICOXIB42
GABAPENTIN42
LACOSAMIDE42
BOTULINUM TOXIN TYPE A41
DICLOFENAC SODIUM41
DULOXETINE41
ESKETAMINE41
ESLICARBAZEPINE ACETATE41
EZOGABINE41
FLUPIRTINE41
OXCARBAZEPINE41
TAPENTADOL41
TRAMADOL41
ZUCAPSAICIN32
CARISBAMATE31
VALNIVUDINE HYDROCHLORIDE31
ADL-5747 FREE BASE23
FUNAPIDE22
ATX08-00121
DWP0519521
KAI-167821
PF-0048979121
PILAVAPADIN21
T-6221
Z16021
CHEMBL405972201

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
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This page pulls from 70 datasets indexed by BioBTree:

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