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Atlas / Disease / Otitis media

Otitis media

disease
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Also known as inflammation of middle earmedial otitismiddle Ear Inflammationotitis media (disease)

Summary

Otitis media (MONDO:0005441) is a disease (an umbrella term covering 8 Mondo subtypes) with 10 cohort genes (40 GWAS associations across 35 studies) and 108 clinical trials. Top therapeutic interventions include ketorolac, montelukast, and streptococcus pneumoniae polysaccharide conjugated to corynebacterium diphtheriae crm197.

At a glance

  • Umbrella term: 8 Mondo subtypes
  • Cohort genes: 10
  • GWAS associations: 40
  • ClinVar variants: 16
  • Clinical trials: 108

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameotitis media
Mondo IDMONDO:0005441
EFOEFO:0004992
MeSHD010033
DOIDDOID:10754
ICD-111079654421
NCITC34885
SNOMED CT65363002
UMLSC0029882
MedGen45253
Is cancer (heuristic)no

Also known as: inflammation of middle ear · medial otitis · middle Ear Inflammation · middle ear inflammation · otitis Media · otitis media (disease)

Data availability: 16 ClinVar variants · 40 GWAS associations (35 studies) · 1 GenCC gene-disease record · 1 HPO phenotype · 4 cell lines.

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › auditory system disorder › middle ear disorder › otitis media

Related subtypes (5): necrosis of ear ossicle, tympanic membrane disorder, eustachian tube disorder, cholesteatoma of middle ear, neoplasm of middle ear

Subtypes (8): middle ear cholesterol granuloma, non-suppurative otitis media, otosalpingitis, suppurative otitis media, allergic otitis media, chronic otitis media, infectious otitis media, tympanitis

Genetics & variants

GWAS landscape

40 GWAS associations across 35 studies. Top hits map to 16 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
chr8:1247126991e-21C0.1
rs117867662e-16ANXA13C0.09
rs104973942e-08JPT1P1 - CBY1P1G1.51
rs169742633e-08PRXA1.75
rs1132354533e-08NUBPLG1.5
chr21:191600743e-08A2.03
rs744004612e-07TJP1?
rs623963815e-07BTBD9 - GLO1G
chr6:282500716e-07?
rs6490577e-07NAMA?
rs69226201e-06BTBD9G
rs47141491e-06BTBD9A
rs78919682e-06RNU6-985P - RN7SKP31?
rs131706572e-06HMHB1 - RN7SL87PC
rs131814802e-06HMHB1 - RN7SL87PC
rs170779683e-06DSE - CBX3P9?
rs93145613e-06RN7SL318P - RPL23AP54?
rs18668623e-06PLCL2A
rs107801203e-06ATP10B - LINC02159G
rs1476475534e-06NREP, STARD4-AS1C
rs2588144e-06NR3C1G
rs98550745e-06CEP70G
rs115451855e-06ZBTB45G
rs131807355e-06LINC02201G
rs100764025e-06MRPS5P3 - SELENOTP2A
rs21795336e-06BTBD9G
rs4217657e-06RNU7-34P - DTWD2G
rs2571417e-06KRT18P16 - LINC01170T
rs42910758e-06RN7SL643P - HTR1ET
rs68608148e-06ZNF608G

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90475902Verma A202423,981394,451Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475903Verma A202416,827406,636Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477802Verma A202411,253416,923Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473478UK Biobank Whole-Genome Sequencing Consortium20259,536448,904Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90667839UK Biobank Whole-Genome Sequencing Consortium20259,536448,904Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90477797Verma A20245,320107,947Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480106Verma A20245,320107,947Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477799Verma A20244,008110,433Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480104Verma A20244,008110,433Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90079935Backman JD20213,333375,772Exome sequencing and analysis of 454,787 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR0
Tier 3: regulatory1
Tier 4: intronic/intergenic32

MAF distribution

BucketVariants
common (>=0.05)29
low_freq (0.01-0.05)2
rare (<0.01)0
unknown2

Functional consequences

ConsequenceCount
intron_variant21
intergenic_variant7
unknown3
TF_binding_site_variant1
synonymous_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
chr8:1247126990.3511e-21Tier 4: intronic/intergenic
rs117867668123703961C>T0.222intron_variantANXA132e-16Tier 4: intronic/intergenic
rs104973942173432931C>A,G,T0.363intergenic_variantJPT1P1 - CBY1P12e-08Tier 4: intronic/intergenic
rs169742631940407632C>T0.094intron_variantPRX3e-08Tier 4: intronic/intergenic
rs1132354531431849939A>G0.05intron_variantNUBPL3e-08Tier 4: intronic/intergenic
chr21:191600743e-08Tier 4: intronic/intergenic
rs744004611529778703T>C0.05intron_variantTJP12e-07Tier 4: intronic/intergenic
rs62396381638669762G>A0.05intron_variantBTBD9 - GLO15e-07Tier 4: intronic/intergenic
chr6:282500716e-07Tier 4: intronic/intergenic
rs649057999472041C>A,G,T0.05intron_variantNAMA7e-07Tier 4: intronic/intergenic
rs6922620638353234G>A,C0.35intron_variantBTBD91e-06Tier 4: intronic/intergenic
rs4714149638355694A>C,G0.05intron_variantBTBD91e-06Tier 4: intronic/intergenic
rs7891968X137829405C>A,T0.05intron_variantRNU6-985P - RN7SKP312e-06Tier 4: intronic/intergenic
rs131706575143908905C>G0.02TF_binding_site_variantHMHB1 - RN7SL87P2e-06Tier 3: regulatory
rs131814805143998887C>G0.05intergenic_variantHMHB1 - RN7SL87P2e-06Tier 4: intronic/intergenic
rs170779686116448435C>A,T0.05intron_variantDSE - CBX3P93e-06Tier 4: intronic/intergenic
rs931456185287261A>C,G,T0.05intron_variantRN7SL318P - RPL23AP543e-06Tier 4: intronic/intergenic
rs1866862316827117T>A0.37intron_variantPLCL23e-06Tier 4: intronic/intergenic
rs107801205160899881A>C,G,T0.17intergenic_variantATP10B - LINC021593e-06Tier 4: intronic/intergenic
rs1476475535111731489CTAA>C,CTAATAA0.04intron_variantNREP, STARD4-AS14e-06Tier 4: intronic/intergenic
rs2588145143296839G>A,T0.32intron_variantNR3C14e-06Tier 4: intronic/intergenic
rs98550743138526086G>A,C0.23intron_variantCEP705e-06Tier 4: intronic/intergenic
rs115451851958517218G>A0.21synonymous_variantZBTB455e-06Tier 4: intronic/intergenic
rs131807355122670630A>C,G,T0.16intron_variantLINC022015e-06Tier 4: intronic/intergenic
rs100764025127166392A>G0.05intergenic_variantMRPS5P3 - SELENOTP25e-06Tier 4: intronic/intergenic
rs2179533638350945T>A,C,G0.05intron_variantBTBD96e-06Tier 4: intronic/intergenic
rs4217655118797202A>G,T0.21intergenic_variantRNU7-34P - DTWD27e-06Tier 4: intronic/intergenic
rs2571415123801004C>A,G,T0.21intergenic_variantKRT18P16 - LINC011707e-06Tier 4: intronic/intergenic
rs4291075686801206T>A,C0.38intron_variantRN7SL643P - HTR1E8e-06Tier 4: intronic/intergenic
rs68608145124705366C>G,T0.33intron_variantZNF6088e-06Tier 4: intronic/intergenic

ClinVar germline variants

16 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 4 conflicting classifications of pathogenicity, 1 benign, 1 likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
617555NM_144670.6(A2ML1):c.10C>T (p.Gln4Ter)A2ML1Likely pathogeniccriteria provided, single submitter
241896NM_144670.6(A2ML1):c.2713-8C>AA2ML1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
384690NM_144670.6(A2ML1):c.2197T>C (p.Phe733Leu)A2ML1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
617554NM_144670.6(A2ML1):c.4061+1G>CA2ML1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
617556NM_144670.6(A2ML1):c.971-8C>TA2ML1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
617557NM_144670.6(A2ML1):c.1308A>C (p.Gln436His)A2ML1Uncertain significancecriteria provided, single submitter
617558NM_144670.6(A2ML1):c.2012T>C (p.Leu671Pro)A2ML1Uncertain significancecriteria provided, single submitter
617559NM_144670.6(A2ML1):c.2329G>A (p.Gly777Arg)A2ML1Uncertain significancecriteria provided, multiple submitters, no conflicts
626339NM_144670.6(A2ML1):c.164C>T (p.Thr55Ile)A2ML1Uncertain significancecriteria provided, multiple submitters, no conflicts
626340NM_144670.6(A2ML1):c.1683G>C (p.Gln561His)A2ML1Uncertain significancecriteria provided, single submitter
626341NM_144670.6(A2ML1):c.2189G>A (p.Arg730His)A2ML1Uncertain significancecriteria provided, multiple submitters, no conflicts
626342NM_144670.6(A2ML1):c.2228C>T (p.Pro743Leu)A2ML1Uncertain significancecriteria provided, single submitter
626343NM_144670.6(A2ML1):c.2545G>T (p.Asp849Tyr)A2ML1Uncertain significancecriteria provided, single submitter
626344NM_144670.6(A2ML1):c.2971G>C (p.Ala991Pro)A2ML1Uncertain significancecriteria provided, single submitter
626345NM_144670.6(A2ML1):c.3491C>T (p.Ala1164Val)A2ML1Uncertain significancecriteria provided, single submitter
413822NM_144670.6(A2ML1):c.3676_3677del (p.Ala1226fs)A2ML1Benigncriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

GeneClassificationInheritanceDiseaseRecords
SLPILimitedAutosomal dominantotitis media

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
CDCA7Orphanet:2268ICF syndrome
PLD3Orphanet:589522Spinocerebellar ataxia type 46

Cohort genes → proteins

10 cohort genes, 10 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only8
multi_evidence2

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SLPIHGNC:11092ENSG00000124107P03973Antileukoproteinasegencc
BLVRBHGNC:1063ENSG00000090013P30043Flavin reductase (NADPH)gwas
SP3HGNC:11208ENSG00000172845Q02447Transcription factor Sp3gwas
CDCA7HGNC:14628ENSG00000144354Q9BWT1Cell division cycle-associated protein 7gwas
PRDX6HGNC:16753ENSG00000117592P30041Peroxiredoxin-6gwas
PLD3HGNC:17158ENSG00000105223Q8IV085’-3’ exonuclease PLD3gwas
SERTAD3HGNC:17931ENSG00000167565Q9UJW9SERTA domain-containing protein 3gwas
SERTAD1HGNC:17932ENSG00000197019Q9UHV2SERTA domain-containing protein 1gwas
HIPK4HGNC:19007ENSG00000160396Q8NE63Homeodomain-interacting protein kinase 4gwas
A2ML1HGNC:23336ENSG00000166535A8K2U0Alpha-2-macroglobulin-like protein 1clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SLPIAntileukoproteinaseAcid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G.
BLVRBFlavin reductase (NADPH)Enzyme that can both act as a NAD(P)H-dependent reductase and a S-nitroso-CoA-dependent nitrosyltransferase.
SP3Transcription factor Sp3Transcriptional factor that can act as an activator or repressor depending on isoform and/or post-translational modifications.
CDCA7Cell division cycle-associated protein 7Participates in MYC-mediated cell transformation and apoptosis; induces anchorage-independent growth and clonogenicity in lymphoblastoid cells.
PRDX6Peroxiredoxin-6Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively.
PLD35’-3’ exonuclease PLD35’->3’ exonuclease that hydrolyzes the phosphodiester bond of single-stranded DNA (ssDNA) and RNA molecules to form nucleoside 3’-monophosphates and 5’-end 5’-hydroxy deoxyribonucleotide/ribonucleotide fragments.
SERTAD3SERTA domain-containing protein 3Antiviral interferon-stimulated protein that plays a role in innate immunity and in the suppression of viruses through different mechanisms.
SERTAD1SERTA domain-containing protein 1Acts at E2F-responsive promoters as coregulator to integrate signals provided by PHD- and/or bromodomain-containing transcription factors.
HIPK4Homeodomain-interacting protein kinase 4Protein kinase that phosphorylates human TP53 at Ser-9, and thus induces TP53 repression of BIRC5 promoter.
A2ML1Alpha-2-macroglobulin-like protein 1Is able to inhibit all four classes of proteinases by a unique ’trapping’ mechanism.

Protein-family classification

Druggable: 4 · Difficult: 2 · Unknown: 4 · Druggable fraction: 0.4

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
Complement126.8×0.184
Kinase12.8×0.433
Enzyme (other)22.4×0.433
Transcription factor21.6×0.433
Other/Unknown40.7×0.907

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SLPIOther/UnknownnoWAP_dom, Elafin-like_sf, WAP_four-disulfide_core
BLVRBEnzyme (other)yes1.3.1.24NAD(P)-bd_dom, NAD(P)-bd_dom_sf, Polyketide_Oxido-like
SP3Transcription factornoZnf_C2H2_type, Znf_C2H2_sf
CDCA7Transcription factornoZnf-4CXXC_R1, CDCA7/CDA7L
PRDX6Enzyme (other)yes1.11.1.27AhpC/TSA, Thioredoxin_domain, Peroxiredoxin_C
PLD3Other/UnknownnoPLipase_D/transphosphatidylase, PLDc_3, Diverse_PLD-related
SERTAD3Other/UnknownnoSERTA_dom, SERTAD3
SERTAD1Other/UnknownnoSERTA_dom, E2F-SERTA_domain_protein
HIPK4KinaseyesProt_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
A2ML1ComplementyesMacroglobln_a2, MG2, Terpenoid_cyclase/PrenylTrfase

Expression context

Cohort genes with no expression data: 0.

9 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)10
unknown0

Top tissues across cohort

TissueCohort genes
lower esophagus mucosa2
mucosa of stomach2
bronchial epithelial cell1
bronchus1
trachea1
monocyte1
trabecular bone tissue1
germinal epithelium of ovary1
hair follicle1
sural nerve1
embryo1
ileal mucosa1
ventricular zone1
corpus epididymis1
gastrocnemius1
adenohypophysis1
pituitary gland1
right frontal lobe1
oocyte1
secondary oocyte1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SLPI262broadmarkertrachea, bronchus, bronchial epithelial cell
BLVRB287ubiquitousmarkertrabecular bone tissue, lower esophagus mucosa, monocyte
SP3299ubiquitousmarkerhair follicle, germinal epithelium of ovary, sural nerve
CDCA7215ubiquitousmarkerileal mucosa, ventricular zone, embryo
PRDX6295ubiquitousmarkercorpus epididymis, gastrocnemius, mucosa of stomach
PLD3282ubiquitousmarkeradenohypophysis, pituitary gland, right frontal lobe
SERTAD3232ubiquitousmarkeroocyte, secondary oocyte, mucosa of stomach
SERTAD1239ubiquitousmarkervena cava, amniotic fluid, lower lobe of lung
HIPK4117tissue_specificyesmale germ line stem cell (sensu Vertebrata) in testis, left testis, right testis
A2ML1176tissue_specificmarkerlower esophagus mucosa, gingiva, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

SymbolInteractor count
PRDX64,106
SP32,624
BLVRB2,475
SLPI2,146
CDCA71,875
PLD31,540
HIPK41,158
A2ML11,128
SERTAD1966
SERTAD3670

Intra-cohort edges

ABSources
CDCA7SP3string_interaction
HIPK4PLD3string_interaction

Structural data

PDB: 6 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
BLVRBP3004323
PLD3Q8IV087
A2ML1A8K2U05
PRDX6P300413
SLPIP039732
CDCA7Q9BWT12

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
HIPK4Q8NE6370.45
SERTAD3Q9UJW967.09
SERTAD1Q9UHV263.69
SP3Q0244738.74

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 10 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Metabolism of porphyrins1285.5×0.031BLVRB
Synthesis of PG1253.8×0.031PLD3
Heme degradation1163.1×0.031BLVRB
Developmental Lineage of Mammary Gland Alveolar Cells1126.9×0.031SLPI
SUMOylation of transcription factors1114.2×0.031SP3
Role of phospholipids in phagocytosis191.4×0.031PLD3
Developmental Lineage of Mammary Gland Luminal Epithelial Cells191.4×0.031SLPI
Detoxification of Reactive Oxygen Species160.1×0.038PRDX6
Neutrophil degranulation29.2×0.038SLPI, PRDX6
Cytoprotection by HMOX1136.8×0.050BLVRB
SUMO E3 ligases SUMOylate target proteins135.7×0.050SP3
SUMOylation132.6×0.050SP3
Cellular response to chemical stress128.6×0.053BLVRB
Cellular responses to stress17.4×0.184BLVRB
Cellular responses to stimuli16.3×0.199BLVRB
Innate Immune System15.1×0.227SLPI
Post-translational protein modification13.8×0.276SP3
Immune System12.6×0.362SLPI
Metabolism of proteins12.5×0.362SP3
Metabolism12.3×0.362BLVRB

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
megakaryocyte differentiation2240.7×0.001BLVRB, SP3
host-mediated perturbation of symbiont process11685.2×0.010SLPI
regulation of endopeptidase activity11685.2×0.010A2ML1
myeloid progenitor cell differentiation1240.7×0.026SP3
myotube differentiation1210.7×0.026PLD3
enucleate erythrocyte differentiation1210.7×0.026SP3
embryonic process involved in female pregnancy1210.7×0.026SP3
cellular oxidant detoxification1187.2×0.026PRDX6
regulation of cytokine production involved in inflammatory response1187.2×0.026PLD3
regulation of DNA-templated transcription39.5×0.026SP3, CDCA7, SERTAD3
heme catabolic process1153.2×0.029BLVRB
granulocyte differentiation1120.4×0.032SP3
embryonic camera-type eye morphogenesis1112.3×0.032SP3
glycerophospholipid catabolic process1105.3×0.032PRDX6
trophectodermal cell differentiation199.1×0.032SP3
definitive hemopoiesis193.6×0.032SP3
natural killer cell differentiation188.7×0.032SP3
monocyte differentiation180.2×0.033SP3
embryonic placenta development176.6×0.033SP3
regulation of cyclin-dependent protein serine/threonine kinase activity173.3×0.033SERTAD1
hydrogen peroxide catabolic process167.4×0.034PRDX6
negative regulation of protein binding162.4×0.035SLPI
positive regulation of mRNA splicing, via spliceosome154.4×0.039PRDX6
immune system process139.2×0.045PLD3
embryonic skeletal system development139.2×0.045SP3
T cell differentiation138.3×0.045SP3
regulation of signal transduction by p53 class mediator138.3×0.045HIPK4
negative regulation of viral genome replication137.5×0.045SLPI
negative regulation of insulin receptor signaling pathway137.5×0.045BLVRB
cell redox homeostasis134.4×0.047PRDX6

Therapeutics

Drugs indicated for this disease

8 approved, 10 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
AmoxicillinApproved (phase 4)
AzithromycinApproved (phase 4)
CefdinirApproved (phase 4)
CefiximeApproved (phase 4)
Cefpodoxime ProxetilApproved (phase 4)
Cefuroxime AxetilApproved (phase 4)
ClarithromycinApproved (phase 4)
TrimethoprimApproved (phase 4)
BenzocainePhase 3 (in late-stage trials)
CiprofloxacinPhase 3 (in late-stage trials)
Clavulanic AcidPhase 3 (in late-stage trials)
DexamethasonePhase 3 (in late-stage trials)
GlycerinPhase 3 (in late-stage trials)
MoxifloxacinPhase 3 (in late-stage trials)
OfloxacinPhase 3 (in late-stage trials)
SyrupPhase 3 (in late-stage trials)
TelithromycinPhase 3 (in late-stage trials)
XylitolPhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Antipyrine, Faropenem Medoxomil, Finafloxacin, Simethicone.

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 8

Druggability breadth: 4 of 10 evidence-associated genes (40%) 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
BLVRBFEBUXOSTAT
HIPK4AFATINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
HIPK4374
BLVRB64
SLPI00
SP300
CDCA700
PRDX600
PLD300
SERTAD300
SERTAD100
A2ML100

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
FEBUXOSTAT4BLVRB
TAMIBAROTENE4BLVRB
ATALUREN4BLVRB
SULFASALAZINE4BLVRB
OLSALAZINE4BLVRB
DEFERASIROX4BLVRB
AFATINIB4HIPK4
FEDRATINIB4HIPK4
SORAFENIB4HIPK4
NERATINIB4HIPK4
AFATINIB DIMALEATE4HIPK4
BOSUTINIB4HIPK4
NINTEDANIB4HIPK4
SUNITINIB4HIPK4
ERLOTINIB4HIPK4
QUIZARTINIB4HIPK4
CRIZOTINIB4HIPK4
MIDOSTAURIN4HIPK4
GEFITINIB4HIPK4
IMATINIB4HIPK4
LINIFANIB3HIPK4
ENZASTAURIN3HIPK4
CANERTINIB3HIPK4
ALVOCIDIB3HIPK4
LESTAURTINIB3HIPK4
RUBOXISTAURIN3HIPK4
FORETINIB2HIPK4
TANDUTINIB2HIPK4
SU-0148132HIPK4
REBASTINIB2HIPK4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

SymbolAssaysType breakdown
HIPK4211Binding:210, Functional:1
PRDX615Binding:15
PLD313Binding:13
BLVRB4Binding:4

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
BLVRB1.3.1.24, 1.5.1.30biliverdin reductase, flavin reductase (NADPH)
PRDX61.11.1.27, 2.3.1.23, 3.1.1.4glutathione-dependent peroxiredoxin, 1-acylglycerophosphocholine O-acyltransferase, phospholipase A2

Cohort genes with high screening signal

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

SymbolChEMBL assays
HIPK4211

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; 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)
FEBUXOSTAT4BLVRB
TAMIBAROTENE4BLVRB
ATALUREN4BLVRB
SULFASALAZINE4BLVRB
OLSALAZINE4BLVRB
DEFERASIROX4BLVRB
AFATINIB4HIPK4
FEDRATINIB4HIPK4
SORAFENIB4HIPK4
NERATINIB4HIPK4
AFATINIB DIMALEATE4HIPK4
BOSUTINIB4HIPK4
NINTEDANIB4HIPK4
SUNITINIB4HIPK4
ERLOTINIB4HIPK4
QUIZARTINIB4HIPK4
CRIZOTINIB4HIPK4
MIDOSTAURIN4HIPK4
GEFITINIB4HIPK4
IMATINIB4HIPK4
LINIFANIB3HIPK4
ENZASTAURIN3HIPK4
CANERTINIB3HIPK4
ALVOCIDIB3HIPK4
LESTAURTINIB3HIPK4
RUBOXISTAURIN3HIPK4
FORETINIB2HIPK4
TANDUTINIB2HIPK4
SU-0148132HIPK4
REBASTINIB2HIPK4

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)2BLVRB, HIPK4
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug2PRDX6, A2ML1
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug6SLPI, SP3, CDCA7, PLD3, SERTAD3, SERTAD1

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
SLPI0—
SP30—
CDCA70—
PRDX615—
PLD313—
SERTAD30—
SERTAD10—
A2ML10—

Clinical trials & evidence

Clinical trials

Clinical trials: 108.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified70
PHASE316
PHASE411
PHASE25
PHASE14
PHASE1/PHASE22

Top trials by phase / activity

NCTPhaseStatusTitle
NCT03655665PHASE4RECRUITINGDoes Topical Otic Drop Use at Time of Tympanostomy Tube Surgery Improve Outcomes When no Middle Ear Effusion is Present
NCT00189462PHASE4COMPLETEDA Pilot Study to Evaluate the Efficacy of Montelukast in the Treatment of Acute Otitis Media (AOM) in Children
NCT00393159PHASE4UNKNOWNThe Influence of The Ear Popper on Serous Otitis Media and on the Accompanying Conductive Hearing Loss in Children
NCT00419380PHASE4COMPLETEDTreatment of Clogged Tympanostomy Tubes: An Off-Label Use of Dornase Alfa (Pulmozyme®)
NCT00539149PHASE4COMPLETEDLong-term Antibiotics for Treatment and Prevention of Otitis Media in Aborignal Children
NCT00956748PHASE4WITHDRAWNN-Acetylcysteine as an Adjunct for Refractory Chronic Suppurative Otitis Media
NCT01174849PHASE4COMPLETEDPneumococcal Vaccines Early and in Combination
NCT01244126PHASE4COMPLETEDPostoperative Effects of Intranasal Fentanyl, IV and IM Morphine in Children Undergoing Myringotomy
NCT01735084PHASE4COMPLETEDUsing Pneumococcal Vaccines in Combination for Maximum Protection From Ear and Lung Infections in First 3 Years of Life
NCT02653742PHASE4UNKNOWNKetorolac Sublingual vs. Fentanyl Intranasal in Pain Control for Bilateral Myringotomy and Tubes (BMT) Placement in Children
NCT04600752PHASE4COMPLETEDStudy to Evaluate the Safety and Clinical Efficacy of Augmentin® Extra Strength-600 in Children With Acute Otitis Media in India
NCT07189572PHASE3NOT_YET_RECRUITINGIntranasal Corticosteroid Spray for Preventing Otitis Media With Effusion After Radiotherapy in Nasopharyngeal Carcinoma
NCT00000363PHASE3COMPLETEDAcute Otitis Media: Adjuvant Therapy to Improve Outcome
NCT00044473PHASE3COMPLETEDA Study of the Effectiness and Safety of Levofloxacin in Treating Children With a Rapid and Severe Onset of Infection and Inflammation of the Middle Ear That is Difficult to Treat
NCT00051753PHASE3COMPLETEDLevofloxacin In The Treatment Of Children With Recurrent And/or Persistent Acute Otitis Media
NCT00174811PHASE3TERMINATEDComparative Study to Evaluate the Efficacy and Safety of Telithromycin Given Once Daily Versus Cefuroxime Axetil Given Twice Daily in Children With Middle Ear Infections
NCT00360100PHASE3COMPLETEDZmax Pediatric Vs Adult Concentration For The Treatment Of Acute Otitis Media
NCT00378417PHASE3COMPLETEDEfficacy Trial of Two Pneumococcal Conjugate Vaccines (PncCRM and PncOMPC) for Prevention of Acute Otitis Media Due to Vaccine Serotypes
NCT00581711PHASE3COMPLETEDImproving Otitis Media Care With Clinical Decision Support
NCT00638534PHASE3COMPLETEDJapanese Study Evaluating the Effects of Telithromycin in Children With Acute Otitis Media
NCT00781521PHASE3COMPLETEDSafety and Efficacy of Floxin Otic Solution in the Treatment of Acute Otitis Media in Children
NCT01619462PHASE3UNKNOWNSafety and Immunogenicity of 10-valent and 13-valent Pneumococcal Conjugate Vaccines in Papua New Guinean Children
NCT02432105PHASE3COMPLETEDSafety and Efficacy of EXE844 Otic Suspension in Otitis Media at Time of Tympanostomy Tube Insertion (OMTT)
NCT02436304PHASE3COMPLETEDSafety and Efficacy of EXE844 Otic Suspension in Otitis Media at Time of Tympanostomy Tube Insertion (OMTT) - Study 2
NCT02600559PHASE3COMPLETEDOpen-Label Study of OTO-201 in Pediatric Subjects With a History of Otitis Media Requiring Tympanostomy Tubes
NCT02703389PHASE3COMPLETEDImproving Knowledge Translation Upon Emergency Department Discharge
NCT04016051PHASE3COMPLETEDAcceptance of Clarithromycin in a Straw Compared to Syrup in Children With Upper Respiratory Tract Infections
NCT00010465PHASE2COMPLETEDNervous System Manipulation and Botanicals for the Treatment of Recurrent Ear Infections in Children
NCT00219401PHASE2COMPLETEDNeonatal Immunization With Pneumococcal Conjugate Vaccine in Papua New Guinea
NCT00276042PHASE2COMPLETEDA Trial to Evaluate Faropenem Medoxomil in the Treatment of Acute Otitis Media
NCT00617682PHASE1/PHASE2COMPLETEDMaternal Immunization To Prevent Infant Otitis Media
NCT01312038PHASE2COMPLETEDEffect of Simethicone on Eustachian Tube Dysfunction
NCT01588535PHASE2COMPLETEDStudy of FAECC Scale (Modified FLACC) to Evaluate Ear Pain in Children With Acute Otitis Media
NCT02817347PHASE1/PHASE2TERMINATEDA Clinical Trial of YH1177 in Patients With Otitis Media and Otorrhea
NCT00001605PHASE1COMPLETEDVaccination for Middle Ear Infection
NCT01908764PHASE1WITHDRAWNPharmacokinetic Study of AL-60371 Otic Suspension in Pediatric Subjects Following Tympanostomy Tube Surgery
NCT02539654PHASE1COMPLETEDPediatric Pharmacokinetic (PK) Study of EXE844 Otic Suspension in Otitis Media at the Time of Tympanostomy Tube Insertion (OMTT)
NCT02592096PHASE1UNKNOWNPazufloxacin Mesilate Ear Drops Clinical Trial Protocol
NCT05348291Not specifiedRECRUITINGEffect of Ventilation Tubes in Otitis-prone Children
NCT05353569Not specifiedRECRUITINGCoherent Optical Detection of Middle Ear Disease

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
KETOROLAC43
MONTELUKAST43
STREPTOCOCCUS PNEUMONIAE POLYSACCHARIDE CONJUGATED TO CORYNEBACTERIUM DIPHTHERIAE CRM19743
LEVOFLOXACIN ANHYDROUS42
TELITHROMYCIN42
AMOXICILLIN41
CLAVULANIC ACID41
FENTANYL41
OFLOXACIN41
PIPERACILLIN41
SIMETHICONE41
TERFENADINE41
BENZOCAINE31
ECHINACEA, UNSPECIFIED31
FAROPENEM MEDOXOMIL31
XYLITOL31
CHEMBL121584802
CHEMBL520512701

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_studyhgncicd11intactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot