◎ Sugi Atlas

Atlas / Disease / Smooth surface dental caries

Smooth surface dental caries

disease
On this page

Summary

Smooth surface dental caries (MONDO:0005592) is a disease with 31 cohort genes (42 GWAS associations across 2 studies). The dominant Reactome pathway is Innate Immune System (8 cohort genes).

At a glance

  • Cohort genes: 31
  • GWAS associations: 42

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namesmooth surface dental caries
Mondo IDMONDO:0005592
UMLSC1456145
MedGen1843464
Is cancer (heuristic)no

Data availability: 42 GWAS associations (2 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › tooth disorder › tooth hard tissue disease › dental caries › smooth surface dental caries

Related subtypes (4): dentin caries, odontoclasia, enamel caries, pit and fissure surface dental caries

Genetics & variants

GWAS landscape

42 GWAS associations across 2 studies. Top hits map to 24 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs20463158e-08RLIG1P3 - RPSAP74T5.19
rs111346542e-07GABRPA4.61
rs10645242e-07ITGALT0.54
rs178260573e-07IRAK3A2.65
rs7237946e-07ZNF827 - Y_RNAG3.65
rs68189647e-07ANKRD17T5.63
rs59676388e-07MIR1321 - SFR1P2A3.48
rs169547769e-07IPO5 - FARP1A5.12
rs14888641e-06CAVIN3 - SMPD1A1.29
rs94710751e-06KIF6A5.25
rs168675791e-06LINC02844 - DUXAP2A8.42
rs171115301e-06TSHR, TSHR-AS1T2.53
rs26777802e-06PROM1A6.35
rs20108092e-06PPIAP21 - RNU6-743PC14.07
rs10792042e-06AAMPA8.45
rs171243722e-06BPIFA4P - BPIFA3T5.2
rs46544382e-06LINC01777 - LINC01646T1.63
rs101763942e-06ARHGAP15T1.77
rs40164292e-06RBMS3C4.56
rs101438662e-06PTGER2 - TXNDC16T1.47
rs168823962e-06TMEM178BC1.16
rs28776492e-06SDR39U1 - CMA1T0.19
rs110820982e-06RPL12P40 - RN7SKP182A1.14
rs104293713e-06RLIG1P3 - RPSAP74C3.8
rs170884393e-06RN7SL401P - FBXO15T2.28
rs61201413e-06BPIFA2T5.08
rs120373433e-06U3 - NXNP1T2.22
rs172365293e-06KPNA4T1.51
rs71387443e-06ITPR2 - INTS13A1.41
rs20323814e-06COX6A1P4 - MTND4LP18G5.69

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST002361Zeng Z201400Genome-wide association study of primary dentition pit-and-fissure and smooth surface caries.
GCST001896Zeng Z201300Genome-wide association studies of pit-and-fissure- and smooth-surface caries in permanent dentition.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding1
Tier 2: splice/UTR1
Tier 3: regulatory0
Tier 4: intronic/intergenic40

MAF distribution

BucketVariants
common (>=0.05)23
low_freq (0.01-0.05)19
rare (<0.01)0
unknown0

Functional consequences

ConsequenceCount
intron_variant26
intergenic_variant13
3_prime_UTR_variant1
missense_variant1
synonymous_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs2046315889198871A>C,G,T0.132intergenic_variantRLIG1P3 - RPSAP748e-08Tier 4: intronic/intergenic
rs111346545170813419A>C0.1733_prime_UTR_variantGABRP2e-07Tier 2: splice/UTR
rs10645241630481502C>A,T0.049missense_variantITGAL2e-07Tier 1: coding
rs178260571266239384G>A,C0.05intron_variantIRAK33e-07Tier 4: intronic/intergenic
rs7237944145954399G>T0.269intergenic_variantZNF827 - Y_RNA6e-07Tier 4: intronic/intergenic
rs6818964473104747C>G,T0.022intron_variantANKRD177e-07Tier 4: intronic/intergenic
rs5967638X85840734G>A0.066intergenic_variantMIR1321 - SFR1P28e-07Tier 4: intronic/intergenic
rs169547761398048363A>G0.016intergenic_variantIPO5 - FARP19e-07Tier 4: intronic/intergenic
rs1488864116321099T>A,C,G0.093intron_variantCAVIN3 - SMPD11e-06Tier 4: intronic/intergenic
rs9471075639339256A>C0.025intron_variantKIF61e-06Tier 4: intronic/intergenic
rs168675798101363039A>C0.015intron_variantLINC02844 - DUXAP21e-06Tier 4: intronic/intergenic
rs171115301481132568T>C0.067intron_variantTSHR, TSHR-AS11e-06Tier 4: intronic/intergenic
rs2677780416020917G>A,C,T0.064intron_variantPROM12e-06Tier 4: intronic/intergenic
rs20108092043362961C>A,G,T0.012intergenic_variantPPIAP21 - RNU6-743P2e-06Tier 4: intronic/intergenic
rs10792042218265791G>A,C0.038intron_variantAAMP2e-06Tier 4: intronic/intergenic
rs171243722033210631T>A,C0.024intergenic_variantBPIFA4P - BPIFA32e-06Tier 4: intronic/intergenic
rs465443814499841T>C0.459intergenic_variantLINC01777 - LINC016462e-06Tier 4: intronic/intergenic
rs101763942143338805T>C0.143intron_variantARHGAP152e-06Tier 4: intronic/intergenic
rs4016429328923310C>G0.016intron_variantRBMS32e-06Tier 4: intronic/intergenic
rs101438661452417637T>C0.117intergenic_variantPTGER2 - TXNDC162e-06Tier 4: intronic/intergenic
rs168823967141188521C>G,T0.015intron_variantTMEM178B2e-06Tier 4: intronic/intergenic
rs28776491424484796T>A,C,G0.034intron_variantSDR39U1 - CMA12e-06Tier 4: intronic/intergenic
rs110820981838618768C>A0.056intergenic_variantRPL12P40 - RN7SKP1822e-06Tier 4: intronic/intergenic
rs10429371888981259C>T0.214intergenic_variantRLIG1P3 - RPSAP743e-06Tier 4: intronic/intergenic
rs170884391873854856T>G0.043intron_variantRN7SL401P - FBXO153e-06Tier 4: intronic/intergenic
rs61201412033180849T>C0.025intron_variantBPIFA23e-06Tier 4: intronic/intergenic
rs120373431218758563G>T0.061intergenic_variantU3 - NXNP13e-06Tier 4: intronic/intergenic
rs172365293160508519C>T0.035intron_variantKPNA43e-06Tier 4: intronic/intergenic
rs71387441226853027A>G0.339intron_variantITPR2 - INTS133e-06Tier 4: intronic/intergenic
rs20323811181524108G>A,C,T0.079intergenic_variantCOX6A1P4 - MTND4LP184e-06Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 12 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
TSHROrphanet:424Familial hyperthyroidism due to mutations in TSH receptor
TSHROrphanet:90673Hypothyroidism due to TSH receptor mutations
TSHROrphanet:95713Athyreosis
TSHROrphanet:95720Thyroid hypoplasia
TSHROrphanet:99819Familial gestational hyperthyroidism
FERMT1Orphanet:2908Kindler epidermolysis bullosa
CHMOrphanet:180Choroideremia
RNASET2Orphanet:85136Cystic leukoencephalopathy without megalencephaly
ANKRD17Orphanet:528084Non-specific syndromic intellectual disability
BBS9Orphanet:110Bardet-Biedl syndrome
CXCR2Orphanet:420699Autosomal recessive severe congenital neutropenia due to CXCR2 deficiency
ITPR2Orphanet:468666Isolated generalized anhidrosis with normal sweat glands

Cohort genes → proteins

31 cohort genes, 30 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only31

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
RPS6KA2HGNC:10431ENSG00000071242Q15349Ribosomal protein S6 kinase alpha-2gwas
TSHRHGNC:12373ENSG00000165409P16473Thyrotropin receptorgwas
FBXO15HGNC:13617ENSG00000141665Q8NCQ5F-box only protein 15gwas
BPIFA1HGNC:15749ENSG00000198183Q9NP55BPI fold-containing family A member 1gwas
FERMT1HGNC:15889ENSG00000101311Q9BQL6Fermitin family homolog 1gwas
BPIFA2HGNC:16203ENSG00000131050Q96DR5BPI fold-containing family A member 2gwas
IRAK3HGNC:17020ENSG00000090376Q9Y616Interleukin-1 receptor-associated kinase 3gwas
LSM5HGNC:17162ENSG00000106355Q9Y4Y9U6 snRNA-associated Sm-like protein LSm5gwas
AAMPHGNC:18ENSG00000127837Q13685Angio-associated migratory cell proteingwas
CHMHGNC:1940ENSG00000188419P24386Rab proteins geranylgeranyltransferase component A 1gwas
TXNDC16HGNC:19965ENSG00000087301Q9P2K2Thioredoxin domain-containing protein 16gwas
BPIFA4PHGNC:20469ENSG00000183566Q86YQ2Putative BPIFA4P proteingwas
ARHGAP15HGNC:21030ENSG00000075884Q53QZ3Rho GTPase-activating protein 15gwas
KIF6HGNC:21202ENSG00000164627Q6ZMV9Kinesin-like protein KIF6gwas
RNASET2HGNC:21686ENSG00000026297O00584Ribonuclease T2gwas
ANKRD17HGNC:23575ENSG00000132466O75179Ankyrin repeat domain-containing protein 17gwas
SIPA1L2HGNC:23800ENSG00000116991Q9P2F8Signal-induced proliferation-associated 1-like protein 2gwas
C1GALT1HGNC:24337ENSG00000106392Q9NS00Glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase 1gwas
NACA4PHGNC:24688ENSG00000228224Q9BZK3Putative nascent polypeptide-associated complex subunit alpha-like proteingwas
SH2D4AHGNC:26102ENSG00000104611Q9H788SH2 domain-containing protein 4Agwas
BBS9HGNC:30000ENSG00000122507Q3SYG4Protein PTHB1gwas
DRD3HGNC:3024ENSG00000151577P35462D(3) dopamine receptorgwas
AJAP1HGNC:30801ENSG00000196581Q9UKB5Adherens junction-associated protein 1gwas
LINC00693HGNC:44526long intergenic non-protein coding RNA 693gwas
CXCR1HGNC:6026ENSG00000163464P25024C-X-C chemokine receptor type 1gwas
CXCR2HGNC:6027ENSG00000180871P25025C-X-C chemokine receptor type 2gwas
ITGALHGNC:6148ENSG00000005844P20701Integrin alpha-Lgwas
ITPR2HGNC:6181ENSG00000123104Q14571Inositol 1,4,5-trisphosphate-gated calcium channel ITPR2gwas
KPNA4HGNC:6397ENSG00000186432O00629Importin subunit alpha-3gwas
IPO5HGNC:6402ENSG00000065150O00410Importin-5gwas
CAVIN3HGNC:9400ENSG00000170955Q969G5Caveolae-associated protein 3gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
RPS6KA2Ribosomal protein S6 kinase alpha-2Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, su…
TSHRThyrotropin receptorReceptor for the thyroid-stimulating hormone (TSH) or thyrotropin.
FBXO15F-box only protein 15Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.
BPIFA1BPI fold-containing family A member 1Lipid-binding protein which shows high specificity for the surfactant phospholipid dipalmitoylphosphatidylcholine (DPPC).
FERMT1Fermitin family homolog 1Involved in cell adhesion.
BPIFA2BPI fold-containing family A member 2Has strong antibacterial activity against P.aeruginosa.
IRAK3Interleukin-1 receptor-associated kinase 3Putative inactive protein kinase which regulates signaling downstream of immune receptors including IL1R and Toll-like receptors.
LSM5U6 snRNA-associated Sm-like protein LSm5Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex).
AAMPAngio-associated migratory cell proteinPlays a role in angiogenesis and cell migration.
CHMRab proteins geranylgeranyltransferase component A 1Substrate-binding subunit of the Rab geranylgeranyltransferase (GGTase) complex.
BPIFA4PPutative BPIFA4P proteinMajor protein in sweat, has surfactant properties.
ARHGAP15Rho GTPase-activating protein 15GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.
RNASET2Ribonuclease T2Ribonuclease that plays an essential role in innate immune response by recognizing and degrading RNAs from microbial pathogens that are subsequently sensed by TLR8.
ANKRD17Ankyrin repeat domain-containing protein 17Could play pivotal roles in cell cycle and DNA regulation.
C1GALT1Glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase 1Glycosyltransferase that generates the core 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins.
SH2D4ASH2 domain-containing protein 4AInhibits estrogen-induced cell proliferation by competing with PLCG for binding to ESR1, blocking the effect of estrogen on PLCG and repressing estrogen-induced proliferation.
BBS9Protein PTHB1The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.
DRD3D(3) dopamine receptorDopamine receptor that is primarily expressed in limbic areas of the brain and is involved in the modulation of cognitive, emotional, and endocrine functions.
AJAP1Adherens junction-associated protein 1Plays a role in cell adhesion and cell migration.
CXCR1C-X-C chemokine receptor type 1Receptor to interleukin-8, which is a powerful neutrophils chemotactic factor.
CXCR2C-X-C chemokine receptor type 2Receptor for interleukin-8 which is a powerful neutrophil chemotactic factor.
ITGALIntegrin alpha-LIntegrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4.
ITPR2Inositol 1,4,5-trisphosphate-gated calcium channel ITPR2Inositol 1,4,5-trisphosphate-gated calcium channel that upon inositol 1,4,5-trisphosphate binding transports calcium from the endoplasmic reticulum lumen to cytoplasm.
KPNA4Importin subunit alpha-3Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1.
IPO5Importin-5Functions in nuclear protein import as nuclear transport receptor.
CAVIN3Caveolae-associated protein 3Regulates the traffic and/or budding of caveolae.

Protein-family classification

Druggable: 11 · Difficult: 6 · Unknown: 14 · 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
Scaffold/PPI63.4×0.055
GPCR43.1×0.136
Ion channel13.6×0.540
Kinase21.8×0.540
Enzyme (other)31.2×0.678
Antibody/Immunoglobulin10.9×0.771
Other/Unknown140.8×0.915

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
RPS6KA2Kinaseyes2.7.11.1Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
TSHRGPCRyesGPCR_Rhodpsn, Gphrmn_rcpt_fam, TSH_rcpt
FBXO15Other/UnknownnoF-box_dom, F-box-like_dom_sf
BPIFA1Other/UnknownnoLipid-bd_serum_glycop_N, Bactericidal_perm-incr_a/b_dom, BPI_fold-superfamily_member
FERMT1Scaffold/PPInoPH_domain, PH-like_dom_sf, FERM_central
BPIFA2Other/UnknownnoLipid-bd_serum_glycop_N, Bactericidal_perm-incr_a/b_dom, BPI_fold-antibacterial
IRAK3KinaseyesDeath_dom, Prot_kinase_dom, Kinase-like_dom_sf
LSM5Other/UnknownnoSm_dom_euk/arc, LSM_dom_sf, LSm5
AAMPScaffold/PPInoWD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
CHMEnzyme (other)yes2.5.1.60Rab_escort, GDP_dissociation_inhibitor, FAD/NAD-bd_sf
TXNDC16Other/UnknownnoThioredoxin_domain, Thioredoxin-like_sf, TXNDC16
BPIFA4POther/UnknownnoLipid-bd_serum_glycop_N, BPI_fold-superfamily_member
ARHGAP15Scaffold/PPInoRhoGAP_dom, PH_domain, Rho_GTPase_activation_prot
KIF6Other/UnknownnoKinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase
RNASET2Enzyme (other)yes4.6.1.19RNase_T2-like, RNase_T2_His_AS_1, RNase_T2_His_AS_2
ANKRD17Scaffold/PPInoAnkyrin_rpt, KH_dom, KH_dom_type_1
SIPA1L2Scaffold/PPInoRap/Ran_GAP_dom, PDZ, SIPA1L_C
C1GALT1Enzyme (other)yes2.4.1.122Fringe-like_glycosylTrfase, C1GALT1/C1GALT1_chp1
NACA4POther/UnknownnoNas_poly-pep-assoc_cplx_dom, EGD2/NACA0like, NAC_A/B_dom_sf
SH2D4AScaffold/PPInoSH2, SH2_dom_sf
BBS9Other/UnknownnoPTHB1, PHTB1_N_dom, PHTB1_GAE_dom
DRD3GPCRyesGPCR_Rhodpsn, Dopamine_rcpt, Dopamine_D3_rcpt
AJAP1Other/UnknownnoAJAP1_PANP_C, AJAP1
LINC00693Other/Unknownno
CXCR1GPCRyesChemokine_CXCR_1/2, GPCR_Rhodpsn, Chemokine_CXCR1
CXCR2GPCRyesChemokine_CXCR2, Chemokine_CXCR_1/2, GPCR_Rhodpsn
ITGALAntibody/ImmunoglobulinyesIntegrin_alpha, VWF_A, FG-GAP
ITPR2Ion channelyesInsP3_rcpt, RIH_dom, Ion_trans_dom
KPNA4Other/UnknownnoArmadillo, Importin-a_IBB, ARM-like
IPO5Other/UnknownnoHEAT, Importin-beta_N, ARM-like
CAVIN3Other/UnknownnoCavin_fam

Expression context

Cohort genes with no expression data: 1.

30 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)30
unknown1

Top tissues across cohort

TissueCohort genes
granulocyte5
blood4
secondary oocyte4
right uterine tube3
calcaneal tendon3
nasal cavity epithelium2
left ventricle myocardium2
leukocyte2
monocyte2
Brodmann (1909) area 232
endothelial cell2
Brodmann (1909) area 462
corpus callosum2
sperm2
oocyte2
inferior olivary complex1
lower lobe of lung1
medial globus pallidus1
left lobe of thyroid gland1
right lobe of thyroid gland1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
RPS6KA2295ubiquitousmarkerinferior olivary complex, lower lobe of lung, medial globus pallidus
TSHR169broadmarkerright lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
FBXO15197broadmarkerbronchial epithelial cell, bronchus, right uterine tube
BPIFA167tissue_specificmarkerolfactory segment of nasal mucosa, nasal cavity epithelium, nasal cavity mucosa
FERMT1235ubiquitousmarkermucosa of sigmoid colon, colonic mucosa, gingival epithelium
BPIFA266tissue_specificmarkerparotid gland, nasal cavity epithelium, left ventricle myocardium
IRAK3238ubiquitousmarkermonocyte, mononuclear cell, leukocyte
LSM5294ubiquitousmarkerventricular zone, ganglionic eminence, embryo
AAMP283ubiquitousmarkerbody of stomach, mucosa of transverse colon, left ovary
CHM264ubiquitousmarkerendothelial cell, Brodmann (1909) area 23, middle temporal gyrus
TXNDC16241ubiquitousmarkerseminal vesicle, corpus epididymis, Brodmann (1909) area 46
BPIFA4P145markerprimordial germ cell in gonad, mucosa of paranasal sinus, endothelial cell
ARHGAP15207broadmarkerblood, bone marrow cell, granulocyte
KIF6190broadmarkerright uterine tube, corpus callosum, sperm
RNASET2291ubiquitousmarkerright uterine tube, granulocyte, blood
ANKRD17292ubiquitousmarkersecondary oocyte, sural nerve, visceral pleura
SIPA1L2254ubiquitousmarkerleft ventricle myocardium, cardiac muscle of right atrium, pons
C1GALT1277ubiquitousmarkeramniotic fluid, secondary oocyte, corpus callosum
NACA4P195ubiquitousmarkerparietal pleura, pleura, superficial temporal artery
SH2D4A235ubiquitousmarkersecondary oocyte, oocyte, calcaneal tendon
BBS9279ubiquitousmarkeroocyte, secondary oocyte, calcaneal tendon
DRD325markermale germ line stem cell (sensu Vertebrata) in testis, metanephric glomerulus, endometrium epithelium
AJAP1178broadmarkerorbitofrontal cortex, Brodmann (1909) area 46, Brodmann (1909) area 23
LINC00693
CXCR1148broadmarkerblood, granulocyte, type B pancreatic cell
CXCR2202broadmarkerblood, periodontal ligament, granulocyte
ITGAL244broadmarkergranulocyte, monocyte, leukocyte
ITPR2273ubiquitousmarkercalcaneal tendon, adrenal tissue, germinal epithelium of ovary
KPNA4289ubiquitousmarkerbiceps brachii, skeletal muscle tissue of biceps brachii, skeletal muscle tissue of rectus abdominis
IPO5305ubiquitousmarkersperm, left testis, male germ cell

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

SymbolInteractor count
KPNA44,085
IPO53,552
CXCR22,717
ANKRD172,536
ITGAL2,448
IRAK32,390
CXCR12,224
RPS6KA21,994
LSM51,965
ITPR21,815

Intra-cohort edges

ABSources
AJAP1KPNA4string_interaction
BPIFA1BPIFA2string_interaction
CXCR1CXCR2string_interaction

Structural data

PDB: 13 · AlphaFold-only: 17 · No structure: 1

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
ITGALP2070141
LSM5Q9Y4Y920
CXCR2P2502520
KPNA4O0062917
TSHRP164739
BPIFA1Q9NP557
DRD3P354627
CXCR1P250245
IRAK3Q9Y6163
IPO5O004103
BBS9Q3SYG42
ARHGAP15Q53QZ31
RNASET2O005841

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
C1GALT1Q9NS0088.43
AAMPQ1368584.55
FERMT1Q9BQL681.14
CHMP2438681.05
TXNDC16Q9P2K280.51
FBXO15Q8NCQ577.42
RPS6KA2Q1534977.37
SH2D4AQ9H78873.71
CAVIN3Q969G572.11
NACA4PQ9BZK371.89
KIF6Q6ZMV971.56
BPIFA4PQ86YQ266.91
BPIFA2Q96DR565.37
SIPA1L2Q9P2F856.59
ANKRD17O7517953.73
AJAP1Q9UKB550.22
ITPR2Q14571

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 152. Enrichment computed across 31 evidence-associated genes (21 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 21 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Innate Immune System89.7×1e-04RPS6KA2, BPIFA1, BPIFA2, IRAK3, AAMP, RNASET2, ITGAL, ITPR2
Immune System95.6×9e-04RPS6KA2, BPIFA1, BPIFA2, IRAK3, AAMP, RNASET2, ITGAL, ITPR2 (+1 more)
vRNP Assembly1271.9×0.080IPO5
Signal amplification1181.3×0.080AAMP
Antimicrobial peptides221.3×0.080BPIFA1, BPIFA2
Signaling by VEGF220.9×0.080AAMP, ITPR2
Chemokine receptors bind chemokines217.8×0.080CXCR1, CXCR2
Toll Like Receptor TLR6:TLR2 Cascade216.7×0.080RPS6KA2, IRAK3
Influenza Infection216.7×0.080KPNA4, IPO5
Toll Like Receptor 2 (TLR2) Cascade216.5×0.080RPS6KA2, IRAK3
Toll Like Receptor TLR1:TLR2 Cascade216.0×0.080RPS6KA2, IRAK3
G alpha (i) signalling events47.4×0.080DRD3, CXCR1, CXCR2, ITPR2
Hemostasis46.9×0.080AAMP, KIF6, ITGAL, ITPR2
Signaling by Receptor Tyrosine Kinases37.4×0.080RPS6KA2, AAMP, ITPR2
MyD88:MAL(TIRAP) cascade initiated on plasma membrane214.5×0.084RPS6KA2, IRAK3
Dopamine receptors1108.8×0.087DRD3
RUNX3 Regulates Immune Response and Cell Migration190.6×0.093ITGAL
CREB phosphorylation177.7×0.093RPS6KA2
Toll Like Receptor 4 (TLR4) Cascade212.5×0.093RPS6KA2, IRAK3
Toll-like Receptor Cascades211.8×0.093RPS6KA2, IRAK3
Neutrophil degranulation44.4×0.093RNASET2, CXCR1, CXCR2, ITGAL
RSK activation168.0×0.097RPS6KA2
Cytokine Signaling in Immune system35.8×0.097RPS6KA2, IRAK3, KPNA4
Platelet activation, signaling and aggregation210.1×0.105AAMP, ITPR2
CLEC7A (Dectin-1) induces NFAT activation149.4×0.122ITPR2
Hormone ligand-binding receptors145.3×0.124TSHR
Deadenylation-dependent mRNA decay141.8×0.124LSM5
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling141.8×0.124RPS6KA2
Gastrin-CREB signalling pathway via PKC and MAPK141.8×0.124RPS6KA2
mRNA decay by 5’ to 3’ exoribonuclease136.2×0.134LSM5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 27 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
positive regulation of macrophage tolerance induction1624.1×0.024IRAK3
regulation of polarized epithelial cell differentiation1624.1×0.024AJAP1
interleukin-8-mediated signaling pathway1624.1×0.024CXCR2
thyroid-stimulating hormone signaling pathway1624.1×0.024TSHR
regulation of protein-containing complex disassembly1624.1×0.024IRAK3
negative regulation of timing of anagen1624.1×0.024FERMT1
presynaptic signal transduction1624.1×0.024SIPA1L2
negative regulation of fermentation1624.1×0.024CAVIN3
cellular response to thyrotropin-releasing hormone1624.1×0.024TSHR
dendritic cell chemotaxis273.4×0.024CXCR1, CXCR2
NLS-bearing protein import into nucleus259.4×0.024KPNA4, IPO5
surfactant homeostasis259.4×0.024BPIFA1, BPIFA4P
brain renin-angiotensin system1312.1×0.032RPS6KA2
immune response in nasopharyngeal-associated lymphoid tissue1312.1×0.032BPIFA1
memory T cell extravasation1312.1×0.032ITGAL
musculoskeletal movement, spinal reflex action1312.1×0.032DRD3
cellular response to carbohydrate stimulus1312.1×0.032RPS6KA2
receptor internalization224.0×0.032CXCR1, CXCR2
protein targeting to membrane221.9×0.035CHM, NACA4P
negative regulation of cell cycle221.5×0.035RPS6KA2, IPO5
neutrophil chemotaxis221.2×0.035CXCR1, CXCR2
acid secretion1208.1×0.035DRD3
negative regulation of single-species biofilm formation in or on host organism1208.1×0.035BPIFA1
cellular response to glycoprotein1208.1×0.035TSHR
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction219.5×0.035DRD3, CAVIN3
response to histamine1156.0×0.039DRD3
negative regulation of protein-containing complex disassembly1156.0×0.039IRAK3
positive regulation of dopamine receptor signaling pathway1156.0×0.039DRD3
positive regulation of MDA-5 signaling pathway1156.0×0.039ANKRD17
circadian regulation of gene expression217.3×0.039DRD3, CAVIN3

Therapeutics

Drug target analysis

Approved (phase 4): 7 · Phase ≥3: 7 · Phased (≥1): 7 · Undrugged: 24

Druggability breadth: 14 of 31 evidence-associated genes (45%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

SymbolExample approved molecule
RPS6KA2FEDRATINIB
TSHRLEVOSALBUTAMOL
IRAK3FEDRATINIB
DRD3CABERGOLINE
CXCR1DEXIBUPROFEN
CXCR2DEXIBUPROFEN
ITGALLOVASTATIN

Top cohort targets by molecule count

SymbolMoleculesMax phase
DRD34484
TSHR3544
IRAK3354
RPS6KA2294
CXCR2134
CXCR194
ITGAL24
FBXO1500
BPIFA100
FERMT100

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
FEDRATINIB4DRD3, IRAK3, RPS6KA2
RUXOLITINIB4RPS6KA2
NERATINIB4RPS6KA2
TOFACITINIB CITRATE4RPS6KA2
TOFACITINIB4RPS6KA2
BOSUTINIB4DRD3, RPS6KA2
BRIGATINIB4RPS6KA2
NINTEDANIB4IRAK3, RPS6KA2
SUNITINIB4DRD3, IRAK3, RPS6KA2
MIDOSTAURIN4IRAK3, RPS6KA2
LEVOSALBUTAMOL4TSHR
PROGESTERONE4TSHR
DICLOFENAC SODIUM4TSHR
CLOTRIMAZOLE4CXCR1, DRD3, TSHR
DAPSONE4TSHR
COLCHICINE4TSHR
OXAPROZIN4DRD3, TSHR
BUMETANIDE4TSHR
GLIPIZIDE4TSHR
CARBAMAZEPINE4TSHR
METHYL SALICYLATE4TSHR
PHENELZINE4TSHR
EDROPHONIUM4TSHR
SULFAPHENAZOLE4TSHR
AMOXAPINE4DRD3, TSHR
PYRIDOSTIGMINE4TSHR
ACETAMINOPHEN4TSHR
DICYCLOMINE4DRD3, TSHR
IODIPAMIDE4TSHR
TESTOSTERONE PROPIONATE4TSHR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

SymbolAssaysType breakdown
DRD31,359Binding:1088, Functional:262, ADMET:6, Unclassified:3
RPS6KA2448Binding:446, ADMET:1, Functional:1
CXCR2272Binding:201, Functional:71
IRAK3147Binding:147
ITGAL146Binding:109, Functional:37
CXCR1120Binding:85, Functional:35
TSHR33Functional:24, Binding:9
IPO513Binding:13
ITPR28Binding:7, Functional:1
FERMT12Binding:2
CHM1Binding:1
KIF61Binding:1
C1GALT11Binding:1
KPNA41Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
RPS6KA22.7.11.1non-specific serine/threonine protein kinase
CHM2.5.1.60protein geranylgeranyltransferase type II
RNASET24.6.1.19ribonuclease T2
C1GALT12.4.1.122N-acetylgalactosaminide beta-1,3-galactosyltransferase

Cohort genes with high screening signal

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

SymbolChEMBL assays
RPS6KA2448
IRAK3147
DRD31,359
CXCR1120
CXCR2272
ITGAL146

Pharmacogenomics

Cohort genes with a PharmGKB record: 28; 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)
FEDRATINIB4DRD3, IRAK3, RPS6KA2
RUXOLITINIB4RPS6KA2
NERATINIB4RPS6KA2
TOFACITINIB CITRATE4RPS6KA2
TOFACITINIB4RPS6KA2
BOSUTINIB4DRD3, RPS6KA2
BRIGATINIB4RPS6KA2
NINTEDANIB4IRAK3, RPS6KA2
SUNITINIB4DRD3, IRAK3, RPS6KA2
MIDOSTAURIN4IRAK3, RPS6KA2
LEVOSALBUTAMOL4TSHR
PROGESTERONE4TSHR
DICLOFENAC SODIUM4TSHR
CLOTRIMAZOLE4CXCR1, DRD3, TSHR
DAPSONE4TSHR
COLCHICINE4TSHR
OXAPROZIN4DRD3, TSHR
BUMETANIDE4TSHR
GLIPIZIDE4TSHR
CARBAMAZEPINE4TSHR
METHYL SALICYLATE4TSHR
PHENELZINE4TSHR
EDROPHONIUM4TSHR
SULFAPHENAZOLE4TSHR
AMOXAPINE4DRD3, TSHR
PYRIDOSTIGMINE4TSHR
ACETAMINOPHEN4TSHR
DICYCLOMINE4DRD3, TSHR
IODIPAMIDE4TSHR
TESTOSTERONE PROPIONATE4TSHR

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)7RPS6KA2, TSHR, IRAK3, DRD3, CXCR1, CXCR2, ITGAL
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug1RNASET2
DDruggable family + AlphaFold only, no drug3CHM, C1GALT1, ITPR2
EDifficult family or no structure, no drug20FBXO15, BPIFA1, FERMT1, BPIFA2, LSM5, AAMP, TXNDC16, BPIFA4P, ARHGAP15, KIF6 (+10 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
FBXO150—
BPIFA10—
FERMT12—
BPIFA20—
LSM50—
AAMP0—
CHM1—
TXNDC160—
BPIFA4P0—
ARHGAP150—
KIF61—
RNASET20—
ANKRD170—
SIPA1L20—
C1GALT11—
NACA4P0—
SH2D4A0—
BBS90—
AJAP10—
LINC006930—
ITPR28—
KPNA41—
IPO513—
CAVIN30—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

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 68

This page pulls from 68 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot