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Atlas / Disease / Chronic rhinosinusitis

Chronic rhinosinusitis

disease
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Also known as chronic sinusitissinusitis, chronic

Summary

Chronic rhinosinusitis (MONDO:0006031) is a disease with 17 cohort genes (133 GWAS associations across 9 studies) and 264 clinical trials. Top therapeutic interventions include sodium chloride, omalizumab, and dexmedetomidine.

At a glance

  • Cohort genes: 17
  • GWAS associations: 133
  • ClinVar variants: 3
  • Clinical trials: 264

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namechronic rhinosinusitis
Mondo IDMONDO:0006031
EFOEFO:1000024
ICD-111836987572
NCITC35151
SNOMED CT40055000
UMLSC0149516
MedGen101751
Is cancer (heuristic)no

Also known as: chronic sinusitis · sinusitis, chronic

Data availability: 3 ClinVar variants · 133 GWAS associations (9 studies) · 6 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › otorhinolaryngologic disease › nasal disorder › paranasal sinus disorder › sinusitis › chronic rhinosinusitis

Related subtypes (4): frontal sinusitis, ethmoid sinusitis, maxillary sinusitis, sphenoid sinusitis

Subtypes (4): chronic frontal sinusitis, chronic maxillary sinusitis, chronic sphenoidal sinusitis, chronic ethmoidal sinusitis

Genetics & variants

GWAS landscape

133 GWAS associations across 9 studies. Top hits map to 37 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs9284124e-94GTF3AP1 - IL33?1.13
rs176125766e-91HLA-DQA1 - HLA-DQB1?1.11
rs18372536e-73BCLAF1P1 - TSLP?0.9
rs14447822e-62LINC02676 - LINC00709?0.91
rs728236411e-58IL18R1, IL1RL1?0.89
rs560621353e-45SMAD3?1.09
rs10110822e-43GSDMB?0.93
rs68942492e-39CARINH, IRF1?0.93
rs92715794e-36HLA-DRB1 - HLA-DQA1A0.2
rs342902852e-34D2HGDH?0.93
rs20950448e-30RANBP6 - GTF3AP1?0.97
rs23951901e-29HLA-DRB9T0.27
rs15042152e-28BACH2?0.94
rs129356578e-28CLEC16A?0.93
rs79363122e-27EMSY - LINC02757?1.06
rs129525812e-27ZNF652-AS1?1.06
rs728363447e-25ACOXL, MIR4435-2HG?1.09
rs30246195e-24IL4R?1.06
rs100757646e-21SPEF2 - IL7R?1.05
rs1177103272e-20SLC7A10 - CEBPA?0.92
rs71739818e-20RORA?1.06
rs19238978e-19UBAC2?0.95
rs47397379e-18RPL13AP18 - RNU6-1213P?0.95
rs619389623e-17RPS26 - ERBB3?1.05
rs38246606e-17GATA3?0.96
rs116185823e-16COG6 - CDKN2AIPNLP3?1.04
rs1677691e-15STAT6?1.04
rs2289531e-15IL2RB?0.96
rs117430292e-15NDFIP1?0.96
rs13913714e-15HLA-DQA1T1.22

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90652529Saarentaus EC202588,965685,602131 genetic loci highlight immunological pathways and tissues in nasal polyposis and asthma.
GCST90269778Saarentaus EC202310,435199,208Inflammatory and infectious upper respiratory diseases associate with 41 genomic loci and type 2 inflammation.
GCST90269789Saarentaus EC202310,435199,208Inflammatory and infectious upper respiratory diseases associate with 41 genomic loci and type 2 inflammation.
GCST90018823Sakaue S20217,529444,966A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90018603Sakaue S20214,617152,226A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90651499Liu TY20253,398185,643Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST012015Soliai M20214832,057Two-stage genome-wide association study of chronic rhinosinusitis and disease subphenotypes highlights mucosal immunity contributing to risk.
GCST007444Kristjansson RP201925113,957A loss-of-function variant in ALOX15 protects against nasal polyps and chronic rhinosinusitis.
GCST90837502Koyama S202500Genetics and context for precision health in Greater Boston.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding1
Tier 2: splice/UTR3
Tier 3: regulatory2
Tier 4: intronic/intergenic44

MAF distribution

BucketVariants
common (>=0.05)49
low_freq (0.01-0.05)0
rare (<0.01)0
unknown1

Functional consequences

ConsequenceCount
intron_variant29
intergenic_variant12
synonymous_variant2
regulatory_region_variant1
5_prime_UTR_variant1
TF_binding_site_variant1
non_coding_transcript_exon_variant1
missense_variant1
3_prime_UTR_variant1
splice_region_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs92841296213148A>C,G,T0.05intergenic_variantGTF3AP1 - IL334e-94Tier 4: intronic/intergenic
rs17612576632647681G>A0.05intergenic_variantHLA-DQA1 - HLA-DQB16e-91Tier 4: intronic/intergenic
rs18372535111066174T>C0.05intron_variantBCLAF1P1 - TSLP6e-73Tier 4: intronic/intergenic
rs1444782109016708G>A0.05intron_variantLINC02676 - LINC007092e-62Tier 4: intronic/intergenic
rs728236412102319699T>A,C0.05intron_variantIL18R1, IL1RL11e-58Tier 4: intronic/intergenic
rs560621351567163292C>T0.05intron_variantSMAD33e-45Tier 4: intronic/intergenic
rs10110821739912261T>A,C,G0.05intron_variantGSDMB2e-43Tier 4: intronic/intergenic
rs68942495132461855A>C,G,T0.05intron_variantCARINH, IRF12e-39Tier 4: intronic/intergenic
rs9271579632622860T>A,C0.05regulatory_region_variantHLA-DRB1 - HLA-DQA14e-36Tier 3: regulatory
rs342902852241759225G>A0.05intron_variantD2HGDH2e-34Tier 4: intronic/intergenic
rs209504496192796T>A,C,G0.05intergenic_variantRANBP6 - GTF3AP18e-30Tier 4: intronic/intergenic
rs2395190632465541C>A,T0.301intron_variantHLA-DRB91e-29Tier 4: intronic/intergenic
rs1504215690296508G>A,C0.055_prime_UTR_variantBACH22e-28Tier 2: splice/UTR
rs129356571611125184G>A,T0.05intron_variantCLEC16A8e-28Tier 4: intronic/intergenic
rs79363121176582682G>C,T0.05intergenic_variantEMSY - LINC027572e-27Tier 4: intronic/intergenic
rs129525811749370984G>A0.05intron_variantZNF652-AS12e-27Tier 4: intronic/intergenic
rs728363442111117122G>A,T0.05intron_variantACOXL, MIR4435-2HG7e-25Tier 4: intronic/intergenic
rs30246191627353485G>A,T0.05intron_variantIL4R5e-24Tier 4: intronic/intergenic
rs10075764535841347A>C,G,T0.05intron_variantSPEF2 - IL7R6e-21Tier 4: intronic/intergenic
rs1177103271933235672C>A0.05TF_binding_site_variantSLC7A10 - CEBPA2e-20Tier 3: regulatory
rs71739811560778755T>C0.05intron_variantRORA8e-20Tier 4: intronic/intergenic
rs19238971399352087T>A,C,G0.05intron_variantUBAC28e-19Tier 4: intronic/intergenic
rs4739737880377390G>C,T0.05non_coding_transcript_exon_variantRPL13AP18 - RNU6-1213P9e-18Tier 4: intronic/intergenic
rs619389621256052982C>T0.05intergenic_variantRPS26 - ERBB33e-17Tier 4: intronic/intergenic
rs3824660108062759C>A,G,T0.05intron_variantGATA36e-17Tier 4: intronic/intergenic
rs116185821339794307A>C,G,T0.05intergenic_variantCOG6 - CDKN2AIPNLP33e-16Tier 4: intronic/intergenic
rs1677691257109992C>T0.05intron_variantSTAT61e-15Tier 4: intronic/intergenic
rs2289532237135396G>A,C,T0.05synonymous_variantIL2RB1e-15Tier 4: intronic/intergenic
rs117430295142129717G>A,C,T0.05intron_variantNDFIP12e-15Tier 4: intronic/intergenic
rs1391371632636021A>C,G,T0.195intergenic_variantHLA-DQA14e-15Tier 4: intronic/intergenic

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

2 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVarVariant (HGVS)GeneClassificationReview
35835NM_000492.4(CFTR):c.2002C>T (p.Arg668Cys)CFTRConflicting classifications of pathogenicitycriteria provided, conflicting classifications
7165NM_000492.4(CFTR):c.1727G>C (p.Gly576Ala)CFTRConflicting classifications of pathogenicitycriteria provided, conflicting classifications
26794246;XY;t(1;14)(q42;q13)Uncertain significancecriteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
CFTROrphanet:399805Male infertility with azoospermia or oligozoospermia due to single gene mutation
CFTROrphanet:48Congenital bilateral absence of vas deferens
CFTROrphanet:498359Aquagenic palmoplantar keratoderma
CFTROrphanet:586Cystic fibrosis
CFTROrphanet:60033Idiopathic bronchiectasis
CFTROrphanet:700124Autosomal recessive hereditary chronic pancreatitis
HLA-DQA1Orphanet:391490Adult-onset myasthenia gravis
HLA-DQA1Orphanet:930Idiopathic achalasia

Cohort genes → proteins

17 cohort genes, 12 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only16
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
STX18HGNC:15942ENSG00000168818Q9P2W9Syntaxin-18gwas
IL33HGNC:16028ENSG00000137033O95760Interleukin-33gwas
CFTRHGNC:1884ENSG00000001626P13569Cystic fibrosis transmembrane conductance regulatorclinvar
WSB2HGNC:19222ENSG00000176871Q9NYS7WD repeat and SOCS box-containing protein 2gwas
BMP10HGNC:20869ENSG00000163217O95393Bone morphogenetic protein 10gwas
CYLC2HGNC:2583ENSG00000155833Q14093Cylicin-2gwas
VSIG10HGNC:26078ENSG00000176834Q8N0Z9V-set and immunoglobulin domain-containing protein 10gwas
LINC00587HGNC:31372ENSG00000204250B1AMM8Putative uncharacterized protein encoded by LINC00587gwas
MIR595HGNC:32851ENSG00000207637microRNA 595gwas
CYYR1-AS1HGNC:39560ENSG00000197934CYYR1 antisense RNA 1gwas
ALOX15HGNC:433ENSG00000161905P16050Polyunsaturated fatty acid lipoxygenase ALOX15gwas
STX18-AS1HGNC:48877ENSG00000247708STX18 antisense RNA 1gwas
HLA-DQA1HGNC:4942ENSG00000196735P01909HLA class II histocompatibility antigen, DQ alpha 1 chaingwas
LINC01888HGNC:52707ENSG00000237576long intergenic non-protein coding RNA 1888gwas
MARCKSP1HGNC:6760myristoylated alanine rich protein kinase C substrate pseudogene 1gwas
PTPRN2HGNC:9677ENSG00000155093Q92932Receptor-type tyrosine-protein phosphatase N2gwas
RFC5HGNC:9973ENSG00000111445P40937Replication factor C subunit 5gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
STX18Syntaxin-18Syntaxin that may be involved in targeting and fusion of Golgi-derived retrograde transport vesicles with the ER.
IL33Interleukin-33Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells.
CFTRCystic fibrosis transmembrane conductance regulatorEpithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis.
WSB2WD repeat and SOCS box-containing protein 2May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
BMP10Bone morphogenetic protein 10Required for maintaining the proliferative activity of embryonic cardiomyocytes by preventing premature activation of the negative cell cycle regulator CDKN1C/p57KIP and maintaining the required expression levels of cardiogenic factors suc…
CYLC2Cylicin-2Plays a role in the establishment of normal sperm morphology during spermatogenesis.
ALOX15Polyunsaturated fatty acid lipoxygenase ALOX15Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators.
HLA-DQA1HLA class II histocompatibility antigen, DQ alpha 1 chainBinds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
PTPRN2Receptor-type tyrosine-protein phosphatase N2Plays a role in vesicle-mediated secretory processes.
RFC5Replication factor C subunit 5Subunit of the replication factor C (RFC) complex which acts during elongation of primed DNA templates by DNA polymerases delta and epsilon, and is necessary for ATP-dependent loading of proliferating cell nuclear antigen (PCNA) onto prime…

Protein-family classification

Druggable: 6 · Difficult: 1 · Unknown: 10 · Druggable fraction: 0.35

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
Phosphatase14.9×0.395
Transporter14.6×0.395
Antibody/Immunoglobulin23.4×0.395
Enzyme (other)21.4×0.602
Other/Unknown101.1×0.602
Scaffold/PPI11.0×0.637

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
STX18Other/UnknownnoSyntaxin/epimorphin_CS, Syntaxin-18_N
IL33Other/UnknownnoIL-33, IL33_C
CFTRTransporteryes2.7.4.3ABC_transporter-like_ATP-bd, AAA+_ATPase, CFTR/ABCC7
WSB2Scaffold/PPInoSOCS_box, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
BMP10Other/UnknownnoTGF-b_propeptide, TGF-b_C, TGF-beta-like
CYLC2Other/UnknownnoCYLC, Cylicin_N
VSIG10Antibody/ImmunoglobulinyesIg_sub2, Ig_sub, Ig-like_dom
LINC00587Other/Unknownno
MIR595Other/Unknownno
CYYR1-AS1Other/Unknownno
ALOX15Enzyme (other)yes1.13.11.31LipOase, PLAT/LH2_dom, LipOase_mml
STX18-AS1Other/Unknownno
HLA-DQA1Antibody/ImmunoglobulinyesMHC_II_a_N, Ig/MHC_CS, Ig_C1-set
LINC01888Other/Unknownno
MARCKSP1Other/Unknownno
PTPRN2Phosphataseyes3.1.3.48PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat
RFC5Enzyme (other)yes3.6.4.B8AAA+_ATPase, ATPase_AAA_core, DNA_pol3_clamp-load_cplx_C

Expression context

Cohort genes with no expression data: 1.

12 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)16
unknown1

Top tissues across cohort

TissueCohort genes
male germ line stem cell (sensu Vertebrata) in testis4
calcaneal tendon2
olfactory segment of nasal mucosa2
gall bladder2
buccal mucosa cell2
rectum2
monocyte2
sural nerve2
endocervix1
endometrium1
right uterine tube1
right coronary artery1
body of pancreas1
pancreas1
orbitofrontal cortex1
postcentral gyrus1
superior frontal gyrus1
cardiac atrium1
cardiac muscle of right atrium1
right atrium auricular region1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
STX18268ubiquitousmarkerright uterine tube, endocervix, endometrium
IL33239broadmarkercalcaneal tendon, right coronary artery, olfactory segment of nasal mucosa
CFTR193broadmarkerbody of pancreas, gall bladder, pancreas
WSB2299ubiquitousmarkersuperior frontal gyrus, postcentral gyrus, orbitofrontal cortex
BMP1090tissue_specificmarkercardiac muscle of right atrium, right atrium auricular region, cardiac atrium
CYLC2114tissue_specificmarkersperm, male germ cell, left testis
VSIG10251ubiquitousmarkerbuccal mucosa cell, rectum, jejunal mucosa
LINC0058750yesmale germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, buccal mucosa cell
MIR59548yesmonocyte, blood, corpus callosum
CYYR1-AS1116broadmarkersural nerve, thymus, male germ line stem cell (sensu Vertebrata) in testis
ALOX15154tissue_specificmarkerolfactory segment of nasal mucosa, bronchial epithelial cell, epithelium of bronchus
STX18-AS1162ubiquitousyesmale germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, sural nerve
HLA-DQA1244broadmarkergall bladder, rectum, monocyte
LINC0188896tissue_specificyesmale germ line stem cell (sensu Vertebrata) in testis, quadriceps femoris, skeletal muscle tissue
MARCKSP1
PTPRN2254broadmarkerlateral nuclear group of thalamus, middle temporal gyrus, lateral globus pallidus
RFC5295ubiquitousmarkerpons, superior vestibular nucleus, body of tongue

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

SymbolInteractor count
CFTR7,664
RFC53,426
IL332,660
WSB22,349
ALOX151,757
STX181,736
PTPRN21,491
BMP101,317
CYLC2690
VSIG10338

Intra-cohort edges

ABSources
CFTRSTX18intact

Structural data

PDB: 6 · AlphaFold-only: 6 · No structure: 5

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
CFTRP1356958
HLA-DQA1P0190928
RFC5P4093716
BMP10O953938
IL33O957605
PTPRN2Q929323

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
ALOX15P1605095.46
WSB2Q9NYS784.84
VSIG10Q8N0Z977.26
STX18Q9P2W973.01
CYLC2Q1409350.39
LINC00587B1AMM846.23

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 76. Enrichment computed across 17 evidence-associated genes (9 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 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Biosynthesis of DPAn-6 SPMs1634.4×0.027ALOX15
Biosynthesis of DPAn-3-derived protectins and resolvins1634.4×0.027ALOX15
RHO GTPases regulate CFTR trafficking1423.0×0.027CFTR
Interleukin-33 signaling1423.0×0.027IL33
Biosynthesis of DPA-derived SPMs1423.0×0.027ALOX15
Biosynthesis of EPA-derived SPMs1317.2×0.027ALOX15
Biosynthesis of protectins1317.2×0.027ALOX15
Biosynthesis of E-series 18(R)-resolvins1317.2×0.027ALOX15
Biosynthesis of DPAn-3 SPMs1317.2×0.027ALOX15
Biosynthesis of E-series 18(S)-resolvins1253.8×0.028ALOX15
Synthesis of 15-eicosatetraenoic acid derivatives1211.5×0.028ALOX15
Biosynthesis of DHA-derived SPMs1211.5×0.028ALOX15
Biosynthesis of specialized proresolving mediators (SPMs)1211.5×0.028ALOX15
Synthesis of 12-eicosatetraenoic acid derivatives1181.3×0.030ALOX15
Polymerase switching190.6×0.050RFC5
Translesion synthesis by REV1179.3×0.050RFC5
Translesion synthesis by POLI174.6×0.050RFC5
Translocation of ZAP-70 to Immunological synapse170.5×0.050HLA-DQA1
Translesion synthesis by POLK170.5×0.050RFC5
Translesion Synthesis by POLH166.8×0.050RFC5
Synthesis of Leukotrienes (LT) and Eoxins (EX)163.4×0.050ALOX15
Arachidonate metabolism163.4×0.050ALOX15
Phosphorylation of CD3 and TCR zeta chains160.4×0.050HLA-DQA1
Co-inhibition by PD-1157.7×0.050HLA-DQA1
PCNA-Dependent Long Patch Base Excision Repair157.7×0.050RFC5
Ub-specific processing proteases211.8×0.050IL33, CFTR
Chaperone Mediated Autophagy155.2×0.051CFTR
Gap-filling DNA repair synthesis and ligation in GG-NER148.8×0.055RFC5
Polymerase switching on the C-strand of the telomere147.0×0.055RFC5
Recognition of DNA damage by PCNA-containing replication complex142.3×0.059RFC5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
positive regulation of cellular defense response11532.0×0.021IL33
negative regulation of macrophage proliferation11532.0×0.021IL33
regulation of engulfment of apoptotic cell11532.0×0.021ALOX15
positive regulation of organelle assembly11532.0×0.021STX18
negative regulation of adaptive immune response1766.0×0.021ALOX15
regulation of peroxisome proliferator activated receptor signaling pathway1766.0×0.021ALOX15
cellular response to interleukin-131766.0×0.021ALOX15
regulation of cardiac muscle hypertrophy in response to stress1766.0×0.021BMP10
intracellular pH elevation1510.7×0.023CFTR
lipoxin A4 biosynthetic process1510.7×0.023ALOX15
microglial cell activation involved in immune response1306.4×0.023IL33
negative regulation of T-helper 1 type immune response1306.4×0.023IL33
transepithelial water transport1306.4×0.023CFTR
positive regulation of enamel mineralization1306.4×0.023CFTR
positive regulation of ER to Golgi vesicle-mediated transport1306.4×0.023STX18
positive regulation of cell proliferation involved in heart morphogenesis1306.4×0.023BMP10
positive regulation of MHC class I biosynthetic process1255.3×0.023IL33
regulation of secretion1255.3×0.023PTPRN2
positive regulation of sarcomere organization1255.3×0.023BMP10
positive regulation of type 2 immune response1218.9×0.023IL33
atrial cardiac muscle tissue morphogenesis1218.9×0.023BMP10
endoplasmic reticulum membrane organization1218.9×0.023STX18
negative regulation of immunoglobulin production1191.5×0.023IL33
positive regulation of glycoprotein biosynthetic process1191.5×0.023IL33
lipid oxidation1191.5×0.023ALOX15
interleukin-33-mediated signaling pathway1191.5×0.023IL33
hepoxilin biosynthetic process1191.5×0.023ALOX15
positive regulation of DNA-directed DNA polymerase activity1191.5×0.023RFC5
phosphatidylethanolamine biosynthetic process1170.2×0.023ALOX15
type 2 immune response1170.2×0.023IL33

Therapeutics

Drugs indicated or in trials for this disease

1 approved drug — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugStatus
MepolizumabApproved (phase 4)

2 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

DrugHighest phase
CiclesonidePhase 3
Fluticasone PropionatePhase 3

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 14

Druggability breadth: 7 of 17 evidence-associated genes (41%) 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
CFTRIVACAFTOR
ALOX15LEVODOPA

Top cohort targets by molecule count

SymbolMoleculesMax phase
ALOX151744
CFTR144
RFC512
STX1800
IL3300
WSB200
BMP1000
CYLC200
VSIG1000
LINC0058700

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
IVACAFTOR4CFTR
LUMACAFTOR4CFTR
TEZACAFTOR4CFTR
ELEXACAFTOR4CFTR
GLYBURIDE4CFTR
LEVODOPA4ALOX15
CANDESARTAN CILEXETIL4ALOX15
DIENESTROL4ALOX15
CLOTRIMAZOLE4ALOX15
CHOLECALCIFEROL4ALOX15
AMINOCAPROIC ACID4ALOX15
FURAZOLIDONE4ALOX15
MIGALASTAT4ALOX15
RALOXIFENE HYDROCHLORIDE4ALOX15
CISPLATIN4ALOX15
RAMIPRIL4ALOX15
CELECOXIB4ALOX15
HYDROXYZINE PAMOATE4ALOX15
MALATHION4ALOX15
PYRITHIONE ZINC4ALOX15
AVOBENZONE4ALOX15
CHLOROXINE4ALOX15
DIBUCAINE HYDROCHLORIDE4ALOX15
FEXOFENADINE HYDROCHLORIDE4ALOX15
PHENOXYBENZAMINE HYDROCHLORIDE4ALOX15
CYCLOPHOSPHAMIDE4ALOX15
ETHOPROPAZINE HYDROCHLORIDE4ALOX15
PHENAZOPYRIDINE HYDROCHLORIDE4ALOX15
PROCHLORPERAZINE EDISYLATE4ALOX15
CARBIDOPA ANHYDROUS4ALOX15

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

SymbolAssaysType breakdown
CFTR520Binding:497, Functional:17, ADMET:5, Toxicity:1
ALOX15242Binding:236, Functional:5, ADMET:1
RFC59Binding:9
HLA-DQA12Binding:2
STX181Binding:1
IL331Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
CFTR2.7.4.3, 5.6.1.6adenylate kinase, channel-conductance-controlling ATPase
ALOX151.13.11.31, 1.13.11.33arachidonate 12-lipoxygenase, arachidonate 15-lipoxygenase
PTPRN23.1.3.48protein-tyrosine-phosphatase
RFC53.6.4.B8

Cohort genes with high screening signal

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

SymbolChEMBL assays
CFTR520
ALOX15242

Pharmacogenomics

Cohort genes with a PharmGKB record: 14; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

SymbolCPIC guidelines
CFTR1

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)
IVACAFTOR4CFTR
LUMACAFTOR4CFTR
TEZACAFTOR4CFTR
ELEXACAFTOR4CFTR
GLYBURIDE4CFTR
LEVODOPA4ALOX15
CANDESARTAN CILEXETIL4ALOX15
DIENESTROL4ALOX15
CLOTRIMAZOLE4ALOX15
CHOLECALCIFEROL4ALOX15
AMINOCAPROIC ACID4ALOX15
FURAZOLIDONE4ALOX15
MIGALASTAT4ALOX15
RALOXIFENE HYDROCHLORIDE4ALOX15
CISPLATIN4ALOX15
RAMIPRIL4ALOX15
CELECOXIB4ALOX15
HYDROXYZINE PAMOATE4ALOX15
MALATHION4ALOX15
PYRITHIONE ZINC4ALOX15
AVOBENZONE4ALOX15
CHLOROXINE4ALOX15
DIBUCAINE HYDROCHLORIDE4ALOX15
FEXOFENADINE HYDROCHLORIDE4ALOX15
PHENOXYBENZAMINE HYDROCHLORIDE4ALOX15
CYCLOPHOSPHAMIDE4ALOX15
ETHOPROPAZINE HYDROCHLORIDE4ALOX15
PHENAZOPYRIDINE HYDROCHLORIDE4ALOX15
PROCHLORPERAZINE EDISYLATE4ALOX15
CARBIDOPA ANHYDROUS4ALOX15

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)2CFTR, ALOX15
BPhased (≥1) drug, not yet approved1RFC5
CDruggable family + PDB, no drug2HLA-DQA1, PTPRN2
DDruggable family + AlphaFold only, no drug1VSIG10
EDifficult family or no structure, no drug11STX18, IL33, WSB2, BMP10, CYLC2, LINC00587, MIR595, CYYR1-AS1, STX18-AS1, LINC01888 (+1 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
STX181—
IL331—
WSB20—
BMP100—
CYLC20—
VSIG100—
LINC005870—
MIR5950—
CYYR1-AS10—
STX18-AS10—
HLA-DQA12—
LINC018880—
MARCKSP10—
PTPRN20—

Clinical trials & evidence

Clinical trials

Clinical trials: 264.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified163
PHASE331
PHASE221
PHASE420
PHASE1/PHASE210
PHASE2/PHASE37
EARLY_PHASE17
PHASE15

Top trials by phase / activity

NCTPhaseStatusTitle
NCT06824649PHASE4NOT_YET_RECRUITINGBiologics in Chronic Rhinosinusitis With Nasal Polyposis
NCT00318006PHASE4COMPLETEDStudy of Nasal Irrigation Versus Nasal Spray for Chronic Nasal and Sinus Symptoms
NCT00396162PHASE4COMPLETEDUse of Probiotics as Adjunctive Treatment for Chronic Rhinosinusitis
NCT00603785PHASE4WITHDRAWNEffects of Anti-IgE Antibody Omalizumab on Patients With Chronic Sinusitis
NCT00671541PHASE4WITHDRAWNNasospore Stent For Use in Enodscopic Sinus Surgery
NCT00754793PHASE4TERMINATEDSinusitis and Facial Pain Disorders Anti-Depression Trial
NCT00841802PHASE4WITHDRAWNChronic Rhinosinusitis With or Without Nasal Polyps Steroid Study
NCT01024075PHASE4UNKNOWNEffect of Sinufoam-Dexamethasone Mixture on Post Endoscopic Sinus Surgery Outcomes
NCT01205984PHASE4COMPLETEDSystemic Methylprednisolone in Chronic Rhinosinusitis
NCT01569048PHASE4COMPLETEDRandomized Controlled Trial to Evaluate of Dexmedetomidine for the Effect on Operative Visibility in Patients Undergoing Endoscopic Sinus Surgery
NCT01575223PHASE4COMPLETEDSaline Irrigation After Surgery in Patients With Chronic Sinusitis
NCT01706952PHASE4COMPLETEDComparison of Topical Vasoconstriction in Endoscopic Sinus Surgery
NCT02218307PHASE4COMPLETEDThe Use of Antibiotic Sinonasal Rinse After Sinus Surgery
NCT02307825PHASE4COMPLETEDAzithromycin for Patients With Chronic Rhinosinusitis Failing Medical and Surgical Therapy
NCT02578862PHASE4COMPLETEDTotal Intravenous Anesthesia in Sinus Surgery
NCT03086070PHASE4COMPLETEDOmeprazole 20 mg in Patients With Laryngopharyngeal reflux and Comorbid Chronic Rhinosinusitis
NCT03705793PHASE4COMPLETEDEffectiveness of Mometasone Nasal Irrigation for Chronic Rhinosinusitis
NCT04754230PHASE4COMPLETEDEffect of Tranexamic Acid on Postoperative Bleeding Following Sinus and Nasal Surgery
NCT04915456PHASE4COMPLETEDEffect of Postoperative Additive Systemic Steroids in CRSwNP
NCT05923047PHASE4UNKNOWNMepolizumab and In-office Nasal Polypectomy in Patients With Chronic Rhinosinusitis (CRS). A Three Arm Study.
NCT05157685PHASE3RECRUITINGEvaluation of the Efficacy of Azithromycin in Idiopathic Purulent Oedematous Sinusitis in Adults
NCT06996951PHASE3RECRUITINGSinonasal Therapies and Histologic Correlations of Patients With Cystic Fibrosis in the Era of Highly Effective Modulator Therapy
NCT07383402PHASE3NOT_YET_RECRUITINGIntra-Sinus Povidone-Iodine and Budesonide After Endoscopic Sinus Surgery for Chronic Rhinosinusitis
NCT00231062PHASE3COMPLETEDClinical Evaluation to Confirm Safety and Efficacy of Sinuplasty in the Paranasal Sinuses (CLEAR)
NCT00265434PHASE3COMPLETEDNasal Inhalation of Dornase Alfa (Pulmozyme) in Patients With Cystic Fibrosis and Chronic Rhinosinusitis
NCT00410735PHASE3COMPLETEDStudy of ONO-1078 in Patients With Chronic Sinusitis
NCT00425620PHASE3COMPLETEDAmphotericin B Suspension in Refractory Chronic Sinusitis
NCT00852410PHASE3UNKNOWNThe Hemostatic and Hemodynamic Effects of Adrenaline During Endoscopic Sinus Surgery
NCT01197612PHASE3COMPLETEDNasal Packing as a Drug Delivery System Postoperatively in Chronic Sinusitis With Polyposis
NCT01253577PHASE3COMPLETEDA Clinical Evaluation of a Steroid-Coated Sinus Stent When Used Following Functional Endoscopic Sinus Surgery in Patients With Chronic Sinusitis
NCT01706484PHASE3COMPLETEDEfficacy and Safety of Two Dosages of a Herbal Medicinal Product (Dry Extract BNO 1016) in Chronic Rhinosinusitis
NCT01732536PHASE2/PHASE3COMPLETEDSteroid-Releasing S8 Sinus Implant for Recurrent Nasal Polyps
NCT01988779PHASE3COMPLETEDOral Versus Topical Antibiotics for Chronic Rhinosinusitis Exacerbations
NCT02106793PHASE3COMPLETEDMitomicin C for Prevention Postoperative Endoscopic Sinus Surgery Synechia and QOL in Chronic Rhinosinusitis
NCT02266810PHASE3COMPLETEDSafety and Efficacy of the Propel Mini and Propel Nova Steroid-Eluting Sinus Implant in Frontal Sinus
NCT02285283PHASE2/PHASE3TERMINATEDItraconazole for Fungal Sensitive Chronic Rhinosinusitis With Nasal Polyps
NCT02291549PHASE3COMPLETEDS8 Sinus Implant in Chronic Sinusitis Patients With Recurrent Nasal Polyps
NCT02367118PHASE3UNKNOWNPrednisone in Chronic Rhinosinusitis Without Nasal Polyps
NCT02746042PHASE3COMPLETEDSinupret Extract Coated Tablets in Chronic Rhinosinusitis
NCT03055507PHASE2/PHASE3COMPLETEDEffect of Post-operative Ibuprofen After Surgery for Chronic Rhinosinusitis

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
SODIUM CHLORIDE48
OMALIZUMAB44
DEXMEDETOMIDINE43
MEPOLIZUMAB43
MOMETASONE FUROATE43
POVIDONE-IODINE43
DUPILUMAB42
ESMOLOL42
MUPIROCIN42
AZITHROMYCIN41
BENRALIZUMAB41
BETAMETHASONE41
COCAINE41
DEXAMETHASONE41
DORNASE ALFA41
EPINEPHRINE41
ESCITALOPRAM41
ITRACONAZOLE41
LABETALOL41
METHYLPREDNISOLONE41
OMEPRAZOLE41
PRANLUKAST41
PREDNISONE41
PROPOFOL41
REMIFENTANIL41
SEVOFLURANE41
TOBRAMYCIN41
XYLITOL33
MEDETOMIDINE31
ETOKIMAB21

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
v1.1.4
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_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncicd11intactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot