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Anxiety disorder

disease
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Also known as anxiety

Summary

Anxiety disorder (MONDO:0005618) is a disease (an umbrella term covering 10 Mondo subtypes) with 29 cohort genes (146 GWAS associations across 59 studies) and 4,026 clinical trials. Top therapeutic interventions include escitalopram, fluoxetine, and paroxetine.

At a glance

  • Umbrella term: 10 Mondo subtypes
  • Cohort genes: 29
  • GWAS associations: 146
  • Clinical trials: 4,026

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameanxiety disorder
Mondo IDMONDO:0005618
EFOEFO:0006788
MeSHD001008
DOIDDOID:2030
NCITC2878
SNOMED CT197480006
UMLSC0003469
MedGen361
Is cancer (heuristic)no

Also known as: anxiety · anxiety disorder

Data availability: 146 GWAS associations (59 studies) · 11 cell lines.

Disease family

An umbrella term covering 10 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › mental disorder › anxiety disorder

Related subtypes (13): akinetopsia, cortical deafness, pain agnosia, tactile agnosia, visual agnosia, psychosexual disorder, drug-induced mental disorder, alcohol-induced mental disorder, adjustment disorder, mood disorder, psychotic disorder, developmental disorder of mental health, disruptive behavior disorder

Subtypes (10): separation anxiety disorder, neurocirculatory asthenia, generalized anxiety disorder, phobic disorder, acute stress disorder, neurotic disorder, panic disorder, obsessive-compulsive disorder, anxiety, mixed anxiety and depressive disorder

Genetics & variants

GWAS landscape

146 GWAS associations across 59 studies. Top hits map to 19 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
chr11:576754102e-16A0.04
chr18:351544805e-15A0.04
chr3:442845842e-14G0.04
chr7:20357983e-14G0.04
chr18:351565373e-14C0.04
rs109595541e-13LINC03131 - JKAMPP1A1.09
chr14:421575452e-13G0.03
rs80095713e-13LRFN5G0.03
rs14411025e-13CAPZBP1 - LINC01965A0.03
chr3:528495496e-13T0.04
rs75062167e-13CELF4C0.04
chr14:419726091e-12T0.03
chr11:1133707583e-12G0.03
rs11111773e-12LRFN5A0.03
chr1:728886544e-12C0.04
chr2:1044543454e-12A0.03
chr2:1442043384e-12C0.03
rs66892265e-12LINC01360T0.01
rs44767487e-12RNU4-69P - RPL23AP44A0.02
chr11:1128277157e-12A0.04
chr11:286518948e-12G0.03
rs79280179e-12DRD2 - TMPRSS5C0.01
chr7:1351034499e-12C0.03
rs75286041e-11PDE4B?1.14
rs46039731e-11SATB1-AS1T0.74
rs71108631e-11NCAM1A0.03
rs111288962e-11SATB1-AS1T0.02
rs48700602e-11ESR1G0.01
chr7:122687172e-11C0.03
chr8:1327334152e-11T0.04

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90476513Verma A2024180,155239,767Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90476514Verma A2024117,865295,381Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90446654Li W202374,973400,243Genome-wide meta-analysis, functional genomics and integrative analyses implicate new risk genes and therapeutic targets for anxiety disorders.
GCST90480756Verma A202460,13551,891Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481760Verma A202460,13551,891Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST008920Zhu Z201946,802359,081Shared Genetics of Asthma and Mental Health Disorders: A Large-Scale Genome-Wide Cross-Trait Analysis.
GCST90473275UK Biobank Whole-Genome Sequencing Consortium202538,796419,644Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90480753Verma A202433,63874,354Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481763Verma A202433,63874,354Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481758Verma A202432,72922,962Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR2
Tier 3: regulatory1
Tier 4: intronic/intergenic47

MAF distribution

BucketVariants
common (>=0.05)49
low_freq (0.01-0.05)1
rare (<0.01)0
unknown0

Functional consequences

ConsequenceCount
intron_variant23
unknown20
intergenic_variant4
5_prime_UTR_variant1
regulatory_region_variant1
3_prime_UTR_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
chr11:576754100.3282e-16Tier 4: intronic/intergenic
chr18:351544800.2475e-15Tier 4: intronic/intergenic
chr3:442845840.4762e-14Tier 4: intronic/intergenic
chr7:20357980.1843e-14Tier 4: intronic/intergenic
chr18:351565370.2473e-14Tier 4: intronic/intergenic
rs10959554911131371A>T0.21intergenic_variantLINC03131 - JKAMPP11e-13Tier 4: intronic/intergenic
chr14:421575450.4072e-13Tier 4: intronic/intergenic
rs80095711441676612G>A,C0.5intron_variantLRFN53e-13Tier 4: intronic/intergenic
rs14411022103863404A>C,G,T0.407intron_variantCAPZBP1 - LINC019655e-13Tier 4: intronic/intergenic
chr3:528495490.3896e-13Tier 4: intronic/intergenic
rs75062161837545899C>T0.238intron_variantCELF47e-13Tier 4: intronic/intergenic
chr14:419726090.4221e-12Tier 4: intronic/intergenic
chr11:1133707580.3583e-12Tier 4: intronic/intergenic
rs11111771441607134A>C,G0.4515_prime_UTR_variantLRFN53e-12Tier 2: splice/UTR
chr1:728886540.1784e-12Tier 4: intronic/intergenic
chr2:1044543450.4624e-12Tier 4: intronic/intergenic
chr2:1442043380.3594e-12Tier 4: intronic/intergenic
rs6689226173341240T>C,G0.05intron_variantLINC013605e-12Tier 4: intronic/intergenic
rs44767485120798862A>G,T0.05intergenic_variantRNU4-69P - RPL23AP447e-12Tier 4: intronic/intergenic
chr11:1128277150.427e-12Tier 4: intronic/intergenic
chr11:286518940.3568e-12Tier 4: intronic/intergenic
rs792801711113578040C>A0.05regulatory_region_variantDRD2 - TMPRSS59e-12Tier 3: regulatory
chr7:1351034490.3859e-12Tier 4: intronic/intergenic
rs7528604165941669G>A,C0.05intron_variantPDE4B1e-11Tier 4: intronic/intergenic
rs4603973318693714T>G0.306intron_variantSATB1-AS11e-11Tier 4: intronic/intergenic
rs711086311112972416A>C,G,T0.425intron_variantNCAM11e-11Tier 4: intronic/intergenic
rs11128896318655438T>A,G0.05intron_variantSATB1-AS12e-11Tier 4: intronic/intergenic
rs48700606151910269G>A0.05intron_variantESR12e-11Tier 4: intronic/intergenic
chr7:122687170.4092e-11Tier 4: intronic/intergenic
chr8:1327334150.1792e-11Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 20 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
GIGYF2Orphanet:411602Hereditary late-onset Parkinson disease
PKD1L1Orphanet:101063Situs inversus totalis
PKD1L1Orphanet:157769Situs ambiguus
CNGB3Orphanet:1871Progressive cone dystrophy
CNGB3Orphanet:49382Achromatopsia
CNGB3Orphanet:827Stargardt disease
TMEM106BOrphanet:100069Semantic dementia
TMEM106BOrphanet:100070Progressive non-fluent aphasia
TMEM106BOrphanet:275864Behavioral variant of frontotemporal dementia
KNL1Orphanet:2512Autosomal recessive primary microcephaly
IQCEOrphanet:93334Postaxial polydactyly type A
KCNJ13Orphanet:65Leber congenital amaurosis
KCNJ13Orphanet:91496Snowflake vitreoretinal degeneration
NTRK2Orphanet:251615Pilomyxoid astrocytoma
NTRK2Orphanet:442835Non-specific early-onset epileptic encephalopathy
NTRK2Orphanet:697160Infantile epileptic spasms syndrome
NTRK2Orphanet:99704Early-onset obesity-hyperphagia-severe developmental delay syndrome
RAD51Orphanet:145Hereditary breast and/or ovarian cancer syndrome
RAD51Orphanet:238722Familial congenital mirror movements
RAD51Orphanet:84Fanconi anemia

Cohort genes → proteins

29 cohort genes, 28 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only29

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
AURKBHGNC:11390ENSG00000178999Q96GD4Aurora kinase Bgwas
GIGYF2HGNC:11960ENSG00000204120Q6Y7W6GRB10-interacting GYF protein 2gwas
PKD1L1HGNC:18053ENSG00000158683Q8TDX9Polycystin-1-like protein 1gwas
SDK1HGNC:19307ENSG00000146555Q7Z5N4Protein sidekick-1gwas
TTC7BHGNC:19858ENSG00000165914Q86TV6Tetratricopeptide repeat protein 7Bgwas
ZFYVE19HGNC:20758ENSG00000166140Q96K21Abscission/NoCut checkpoint regulatorgwas
CNGB3HGNC:2153ENSG00000170289Q9NQW8Cyclic nucleotide-gated channel beta-3gwas
TMEM106BHGNC:22407ENSG00000106460Q9NUM4Transmembrane protein 106Bgwas
ADCY2HGNC:233ENSG00000078295Q08462Adenylate cyclase type 2gwas
DUSP29HGNC:23481ENSG00000188716Q68J44Dual specificity phosphatase 29gwas
KNL1HGNC:24054ENSG00000137812Q8NG31Outer kinetochore KNL1 complex subunit KNL1gwas
RMDN3HGNC:25550ENSG00000137824Q96TC7Regulator of microtubule dynamics protein 3gwas
DNAJC17HGNC:25556ENSG00000104129Q9NVM6DnaJ homolog subfamily C member 17gwas
MFAP3LHGNC:29083ENSG00000198948O75121Microfibrillar-associated protein 3-likegwas
IQCEHGNC:29171ENSG00000106012Q6IPM2IQ domain-containing protein Egwas
TMEM132DHGNC:29411ENSG00000151952Q14C87Transmembrane protein 132Dgwas
MYH15HGNC:31073ENSG00000144821Q9Y2K3Myosin-15gwas
EDIL3HGNC:3173ENSG00000164176O43854EGF-like repeat and discoidin I-like domain-containing protein 3gwas
C15orf62HGNC:34489ENSG00000188277A8K5M9Uncharacterized protein C15orf62, mitochondrialgwas
GCHFRHGNC:4194ENSG00000137880P30047GTP cyclohydrolase 1 feedback regulatory proteingwas
CXCL1HGNC:4602ENSG00000163739P09341Growth-regulated alpha proteingwas
GUCY1A2HGNC:4684ENSG00000152402P33402Guanylate cyclase soluble subunit alpha-2gwas
RAD51-AS1HGNC:48621ENSG00000245849RAD51 antisense RNA 1gwas
KCNJ13HGNC:6259ENSG00000115474O60928Inward rectifier potassium channel 13gwas
NTRK2HGNC:8032ENSG00000148053Q16620BDNF/NT-3 growth factors receptorgwas
OR8A1HGNC:8469ENSG00000196119Q8NGG7Olfactory receptor 8A1gwas
PDE4BHGNC:8781ENSG00000184588Q073433’,5’-cyclic-AMP phosphodiesterase 4Bgwas
PTPRTHGNC:9682ENSG00000196090O14522Receptor-type tyrosine-protein phosphatase Tgwas
RAD51HGNC:9817ENSG00000051180Q06609DNA repair protein RAD51 homolog 1gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
AURKBAurora kinase BSerine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis.
GIGYF2GRB10-interacting GYF protein 2Key component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation.
PKD1L1Polycystin-1-like protein 1Component of a calcium-permeant ion channel formed by PKD1L2 and PKD1L1 in primary cilia, where it controls cilium calcium concentration, without affecting cytoplasmic calcium concentration, and regulates sonic hedgehog/SHH signaling and G…
SDK1Protein sidekick-1Adhesion molecule that promotes lamina-specific synaptic connections in the retina.
TTC7BTetratricopeptide repeat protein 7BComponent of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane.
ZFYVE19Abscission/NoCut checkpoint regulatorKey regulator of abscission step in cytokinesis: part of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage.
CNGB3Cyclic nucleotide-gated channel beta-3Pore-forming subunit of the cone cyclic nucleotide-gated channel.
TMEM106BTransmembrane protein 106BIn neurons, involved in the transport of late endosomes/lysosomes.
ADCY2Adenylate cyclase type 2Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.
DUSP29Dual specificity phosphatase 29Dual specificity phosphatase able to dephosphorylate phosphotyrosine, phosphoserine and phosphothreonine residues within the same substrate, with a preference for phosphotyrosine as a substrate.
KNL1Outer kinetochore KNL1 complex subunit KNL1Acts as a component of the outer kinetochore KNL1 complex that serves as a docking point for spindle assembly checkpoint components and mediates microtubule-kinetochore interactions.
RMDN3Regulator of microtubule dynamics protein 3Involved in cellular calcium homeostasis regulation.
DNAJC17DnaJ homolog subfamily C member 17May negatively affect PAX8-induced thyroglobulin/TG transcription.
MFAP3LMicrofibrillar-associated protein 3-likeMay participate in the nuclear signaling of EGFR and MAPK1/ERK2.
IQCEIQ domain-containing protein EComponent of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling.
TMEM132DTransmembrane protein 132DRegulate neuronals morphology via inhibition of the WAVE regulatory complex (WCR), a complex that controls F-actin cytoskeletal dynamics.
MYH15Myosin-15Muscle contraction.
EDIL3EGF-like repeat and discoidin I-like domain-containing protein 3Promotes adhesion of endothelial cells through interaction with the alpha-v/beta-3 integrin receptor.
GCHFRGTP cyclohydrolase 1 feedback regulatory proteinMediates tetrahydrobiopterin inhibition of GTP cyclohydrolase 1.
CXCL1Growth-regulated alpha proteinHas chemotactic activity for neutrophils.
GUCY1A2Guanylate cyclase soluble subunit alpha-2Has guanylyl cyclase on binding to the beta-1 subunit.
KCNJ13Inward rectifier potassium channel 13Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it.
NTRK2BDNF/NT-3 growth factors receptorReceptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticit…
OR8A1Olfactory receptor 8A1Odorant receptor.
PDE4B3’,5’-cyclic-AMP phosphodiesterase 4BHydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
PTPRTReceptor-type tyrosine-protein phosphatase TMay be involved in both signal transduction and cellular adhesion in the CNS.
RAD51DNA repair protein RAD51 homolog 1Plays an important role in homologous strand exchange, a key step in DNA repair through homologous recombination (HR).

Protein-family classification

Druggable: 12 · Difficult: 4 · Unknown: 13 · Druggable fraction: 0.41

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
Ion channel27.7×0.209
Phosphatase25.8×0.209
Antibody/Immunoglobulin33.0×0.227
Kinase21.9×0.633
Transcription factor30.8×0.913
Enzyme (other)20.8×0.913
GPCR10.8×0.913
Other/Unknown130.8×0.916
Scaffold/PPI10.6×0.916

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
AURKBKinaseyesProt_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
GIGYF2Other/UnknownnoGYF, GYF-like_dom_sf, GRB10-interact_GYF
PKD1L1Antibody/ImmunoglobulinyesPKD_dom, PLAT/LH2_dom, PKD/REJ-like
SDK1Antibody/ImmunoglobulinyesIg_sub2, Ig_sub, FN3_dom
TTC7BOther/UnknownnoTPR-like_helical_dom_sf, TPR_rpt, TTC7_N
ZFYVE19Transcription factornoZnf_FYVE, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
CNGB3Ion channelyescNMP-bd_dom, Ion_trans_dom, RmlC-like_jellyroll
TMEM106BOther/UnknownnoTMEM106, TMEM106_C, TMEM106_N
ADCY2Enzyme (other)yes4.6.1.1A/G_cyclase, Adcy_conserved_dom, A/G_cyclase_CS
DUSP29PhosphataseyesDual-sp_phosphatase_cat-dom, Tyr_Pase_dom, Tyr_Pase_AS
KNL1Other/UnknownnoBlinkin, Knl1_RWD_C, KNL1_MELT_rpt
RMDN3Other/UnknownnoTPR-like_helical_dom_sf,
DNAJC17Other/UnknownnoRRM_dom, DnaJ_domain, Nucleotide-bd_a/b_plait_sf
MFAP3LAntibody/ImmunoglobulinyesIg_sub2, Ig_sub, Ig-like_dom
IQCEOther/UnknownnoIQ_motif_EF-hand-BS, CellDiv_DevSignal_Domain
TMEM132DOther/UnknownnoTMEM132, TMEM132_N, TMEM132_C
MYH15Scaffold/PPInoMyosin_head_motor_dom-like, Myosin_tail, SH3_Myosin
EDIL3Other/UnknownnoEGF-type_Asp/Asn_hydroxyl_site, FA58C, EGF
C15orf62Other/UnknownnoCdc42_Effector_BORG/CEP
GCHFROther/UnknownnoGTP_CycHdrlase_I_reg, GFRP_sf
CXCL1Other/UnknownnoChemokine_CXC, Chemokine_IL8-like_dom, Chemokine_CXC_CS
GUCY1A2Enzyme (other)yes4.6.1.2A/G_cyclase, Heme_NO-bd, HNOB_dom_associated
RAD51-AS1Other/Unknownno
KCNJ13Ion channelyesKCNJ13, K_chnl_inward-rec_Kir_cyto, Ig_E-set
NTRK2Kinaseyes2.7.10.1LRRNT, Cys-rich_flank_reg_C, Prot_kinase_dom
OR8A1GPCRyesGPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
PDE4BTranscription factorno3.1.4.53PDEase_catalytic_dom, HD/PDEase_dom, PDEase
PTPRTPhosphataseyes3.1.3.48PTP_cat, Tyr_Pase_dom, MAM_dom
RAD51Transcription factorno3.6.4.B7AAA+_ATPase, DNA_repair_Rad51/TF_NusA_a-hlx, DNA_recomb/repair_Rad51

Expression context

Cohort genes with no expression data: 0.

26 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)1
broad (>20)28
unknown0

Top tissues across cohort

TissueCohort genes
sural nerve4
male germ line stem cell (sensu Vertebrata) in testis4
primordial germ cell in gonad4
Brodmann (1909) area 234
ventricular zone3
cerebellar hemisphere3
lower esophagus mucosa3
pigmented layer of retina3
middle temporal gyrus3
calcaneal tendon2
lateral nuclear group of thalamus2
C1 segment of cervical spinal cord2
olfactory segment of nasal mucosa2
choroid plexus epithelium2
lateral globus pallidus2
buccal mucosa cell2
ganglionic eminence1
oocyte1
colonic epithelium1
apex of heart1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
AURKB187ubiquitousmarkerventricular zone, ganglionic eminence, oocyte
GIGYF2291ubiquitousmarkercalcaneal tendon, sural nerve, colonic epithelium
PKD1L1150tissue_specificmarkermale germ line stem cell (sensu Vertebrata) in testis, apex of heart, primordial germ cell in gonad
SDK1183broadmarkerpopliteal artery, decidua, tibial artery
TTC7B245ubiquitousmarkerlateral nuclear group of thalamus, cerebellar cortex, cerebellar hemisphere
ZFYVE19211ubiquitousmarkerlower esophagus mucosa, mucosa of transverse colon, C1 segment of cervical spinal cord
CNGB3161tissue_specificmarkermale germ line stem cell (sensu Vertebrata) in testis, pigmented layer of retina, diaphragm
TMEM106B286ubiquitousmarkercaput epididymis, corpus epididymis, cauda epididymis
ADCY2254broadmarkermiddle temporal gyrus, Brodmann (1909) area 23, dorsal motor nucleus of vagus nerve
DUSP2955tissue_specificyeshindlimb stylopod muscle, gastrocnemius, muscle of leg
KNL1193ubiquitousmarkermale germ line stem cell (sensu Vertebrata) in testis, ventricular zone, primordial germ cell in gonad
RMDN3281ubiquitousmarkerileal mucosa, C1 segment of cervical spinal cord, cerebellar hemisphere
DNAJC17193ubiquitousmarkersural nerve, calcaneal tendon, olfactory segment of nasal mucosa
MFAP3L265ubiquitousmarkersperm, choroid plexus epithelium, pigmented layer of retina
IQCE231ubiquitousmarkerleft testis, right testis, sural nerve
TMEM132D79broadmarkermiddle temporal gyrus, Brodmann (1909) area 23, Brodmann (1909) area 46
MYH15135tissue_specificmarkerparaflocculus, frontal pole, middle frontal gyrus
EDIL3274ubiquitousmarkerlateral globus pallidus, inferior vagus X ganglion, substantia nigra pars reticulata
C15orf62170tissue_specificyeslower esophagus mucosa, buccal mucosa cell, esophagus mucosa
GCHFR215ubiquitousmarkerright lobe of liver, liver, lower esophagus mucosa
CXCL1240ubiquitousmarkerolfactory segment of nasal mucosa, periodontal ligament, spleen
GUCY1A2234broadmarkerBrodmann (1909) area 23, lateral nuclear group of thalamus, visceral pleura
RAD51-AS1194ubiquitousyesright uterine tube, right lobe of thyroid gland, cerebellar hemisphere
KCNJ13166broadmarkerchoroid plexus epithelium, pigmented layer of retina, retina
NTRK2273broadmarkercranial nerve II, lateral globus pallidus, CA1 field of hippocampus
OR8A117markermale germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, sural nerve
PDE4B287ubiquitousmarkercorpus callosum, cartilage tissue, subthalamic nucleus
PTPRT131broadmarkerBrodmann (1909) area 10, middle temporal gyrus, Brodmann (1909) area 23
RAD51193ubiquitousmarkerprimordial germ cell in gonad, buccal mucosa cell, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

SymbolInteractor count
RAD516,465
AURKB6,131
NTRK25,190
KNL13,438
CXCL13,376
GIGYF22,914
RMDN32,665
PTPRT2,373
EDIL31,947
ADCY21,629

Intra-cohort edges

ABSources
AURKBKNL1string_interaction
AURKBZFYVE19string_interaction
C15orf62DNAJC17string_interaction
C15orf62ZFYVE19string_interaction
DNAJC17ZFYVE19string_interaction

Structural data

PDB: 17 · AlphaFold-only: 11 · No structure: 1

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
RAD51Q0660952
PDE4BQ0734343
TMEM106BQ9NUM429
CNGB3Q9NQW89
NTRK2Q166209
GCHFRP300478
CXCL1P093418
KNL1Q8NG317
TTC7BQ86TV65
KCNJ13O609285
GIGYF2Q6Y7W63
AURKBQ96GD41
DUSP29Q68J441
RMDN3Q96TC71
DNAJC17Q9NVM61
EDIL3O438541
PTPRTO145221

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
OR8A1Q8NGG787.02
ADCY2Q0846278.91
GUCY1A2P3340276.88
MYH15Q9Y2K374.58
SDK1Q7Z5N472.92
TMEM132DQ14C8770.52
ZFYVE19Q96K2169.82
IQCEQ6IPM269.36
MFAP3LO7512161.86
C15orf62A8K5M961.19
PKD1L1Q8TDX9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 124. Enrichment computed across 29 evidence-associated genes (13 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 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
SDK interactions1439.2×0.047SDK1
BDNF activates NTRK2 (TRKB) signaling1439.2×0.047NTRK2
NTF3 activates NTRK2 (TRKB) signaling1439.2×0.047NTRK2
NTF4 activates NTRK2 (TRKB) signaling1439.2×0.047NTRK2
Amplification of signal from the kinetochores230.3×0.047AURKB, KNL1
Signaling by Hedgehog228.3×0.047ADCY2, IQCE
Mitotic Spindle Checkpoint224.4×0.052AURKB, KNL1
Activated NTRK2 signals through PLCG11219.6×0.061NTRK2
NGF-independant TRKA activation1175.7×0.061NTRK2
Activated NTRK2 signals through FYN1146.4×0.061NTRK2
NTRK2 activates RAC11146.4×0.061NTRK2
Activated NTRK2 signals through CDK51146.4×0.061NTRK2
Activated NTRK2 signals through PI3K1125.5×0.061NTRK2
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal217.9×0.061AURKB, KNL1
Mitotic Metaphase and Anaphase214.9×0.061AURKB, KNL1
Mitotic Anaphase214.9×0.061AURKB, KNL1
EML4 and NUDC in mitotic spindle formation214.3×0.061AURKB, KNL1
Cell Cycle Checkpoints213.6×0.062AURKB, KNL1
Resolution of Sister Chromatid Cohesion213.3×0.062AURKB, KNL1
Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation187.8×0.063GCHFR
Adenylate cyclase activating pathway187.8×0.063ADCY2
Activated NTRK2 signals through RAS187.8×0.063NTRK2
RHO GTPases Activate Formins211.9×0.063AURKB, KNL1
Activated NTRK2 signals through FRS2 and FRS3173.2×0.068NTRK2
Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition167.6×0.068EDIL3
Nitric oxide stimulates guanylate cyclase162.8×0.068GUCY1A2
Mitotic Prometaphase210.7×0.068AURKB, KNL1
RHO GTPase Effectors210.5×0.068AURKB, KNL1
M Phase210.2×0.068AURKB, KNL1
Adenylate cyclase inhibitory pathway158.6×0.070ADCY2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 26 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
mitotic cytokinesis checkpoint signaling2324.1×0.003AURKB, ZFYVE19
negative regulation of cytokinesis2185.2×0.005AURKB, ZFYVE19
protein localization to kinetochore2108.0×0.010AURKB, KNL1
midbody abscission256.4×0.029AURKB, ZFYVE19
response to glucoside1648.1×0.039RAD51
positive regulation of lateral attachment of mitotic spindle microtubules to kinetochore1648.1×0.039AURKB
positive regulation of meiosis I spindle assembly checkpoint1648.1×0.039KNL1
spliceosomal complex disassembly1324.1×0.039DNAJC17
negative regulation of biosynthetic process1324.1×0.039GCHFR
homologous chromosome orientation in meiotic metaphase I1324.1×0.039KNL1
negative regulation of small molecule metabolic process1324.1×0.039GCHFR
repair of mitotic kinetochore microtubule attachment defect1324.1×0.039AURKB
negative regulation of relaxation of cardiac muscle1324.1×0.039PDE4B
mitotic recombination-dependent replication fork processing1324.1×0.039RAD51
mitotic sister chromatid biorientation1324.1×0.039AURKB
feeding behavior241.8×0.039GIGYF2, NTRK2
DNA recombinase assembly1216.1×0.045RAD51
detection of nodal flow1216.1×0.045PKD1L1
cell cycle G2/M phase transition1216.1×0.045AURKB
positive regulation of mitotic sister chromatid segregation1216.1×0.045AURKB
trans-synaptic signaling by BDNF, modulating synaptic transmission1216.1×0.045NTRK2
obsolete positive regulation of nitric oxide mediated signal transduction1162.0×0.046GUCY1A2
post-transcriptional gene silencing1162.0×0.046GIGYF2
DNA strand invasion1162.0×0.046RAD51
response to oxygen levels1162.0×0.046GUCY1A2
positive regulation of mitotic sister chromatid separation1162.0×0.046AURKB
positive regulation of microtubule depolymerization1129.6×0.046AURKB
brain-derived neurotrophic factor receptor signaling pathway1129.6×0.046NTRK2
mechanoreceptor differentiation1129.6×0.046NTRK2
chromosome organization involved in meiotic cell cycle1129.6×0.046RAD51

Therapeutics

Drugs indicated for this disease

8 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
AlprazolamApproved (phase 4)
ChlordiazepoxideApproved (phase 4)
DiazepamApproved (phase 4)
LorazepamApproved (phase 4)
MeprobamateApproved (phase 4)
OxazepamApproved (phase 4)
PregabalinApproved (phase 4)
ProchlorperazineApproved (phase 4)
FluoxetinePhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Fasedienol, Propranolol.

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 4 · Undrugged: 25

Druggability breadth: 8 of 29 evidence-associated genes (28%) 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
AURKBSORAFENIB TOSYLATE
GUCY1A2BENZYDAMINE
NTRK2FEDRATINIB
PDE4BINAMRINONE

Top cohort targets by molecule count

SymbolMoleculesMax phase
AURKB824
PDE4B554
NTRK2504
GUCY1A214
GIGYF200
PKD1L100
SDK100
TTC7B00
ZFYVE1900
CNGB300

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
SORAFENIB TOSYLATE4AURKB
FEDRATINIB4AURKB, NTRK2
TIVOZANIB4AURKB
LENVATINIB4AURKB
AXITINIB4AURKB
SORAFENIB4AURKB, NTRK2
ENTRECTINIB4AURKB, NTRK2
BELUMOSUDIL4AURKB
PACRITINIB4AURKB
FOSTAMATINIB4AURKB
TOFACITINIB4AURKB
VANDETANIB4AURKB
UPADACITINIB4AURKB
PEXIDARTINIB4AURKB
PAZOPANIB4AURKB
NINTEDANIB4AURKB, NTRK2
SUNITINIB4AURKB, NTRK2
DASATINIB4AURKB
ERLOTINIB4AURKB
LAPATINIB4AURKB
QUIZARTINIB4AURKB, NTRK2
CRIZOTINIB4AURKB, NTRK2
MIDOSTAURIN4AURKB, NTRK2
INAMRINONE4AURKB, PDE4B
CABOZANTINIB4AURKB
BENZYDAMINE4GUCY1A2
RUXOLITINIB4NTRK2
INFIGRATINIB PHOSPHATE4NTRK2
INFIGRATINIB4NTRK2
CERITINIB4NTRK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

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

SymbolAssaysType breakdown
AURKB1,227Binding:1199, ADMET:22, Functional:6
PDE4B796Binding:755, Functional:29, ADMET:11, Toxicity:1
NTRK2554Binding:547, ADMET:5, Functional:2
RAD51124Binding:116, ADMET:8
GUCY1A232Binding:27, Functional:5
ADCY231Binding:29, Functional:2
KCNJ139Binding:9
GIGYF25Binding:5

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
ADCY24.6.1.1adenylate cyclase
GUCY1A24.6.1.2guanylate cyclase
NTRK22.7.10.1receptor protein-tyrosine kinase
PDE4B3.1.4.533’,5’-cyclic-AMP phosphodiesterase
PTPRT3.1.3.48protein-tyrosine-phosphatase
RAD513.6.4.B7

Cohort genes with high screening signal

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

SymbolChEMBL assays
AURKB1,227
NTRK2554
PDE4B796
RAD51124

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)
SORAFENIB TOSYLATE4AURKB
FEDRATINIB4AURKB, NTRK2
TIVOZANIB4AURKB
LENVATINIB4AURKB
AXITINIB4AURKB
SORAFENIB4AURKB, NTRK2
ENTRECTINIB4AURKB, NTRK2
BELUMOSUDIL4AURKB
PACRITINIB4AURKB
FOSTAMATINIB4AURKB
TOFACITINIB4AURKB
VANDETANIB4AURKB
UPADACITINIB4AURKB
PEXIDARTINIB4AURKB
PAZOPANIB4AURKB
NINTEDANIB4AURKB, NTRK2
SUNITINIB4AURKB, NTRK2
DASATINIB4AURKB
ERLOTINIB4AURKB
LAPATINIB4AURKB
QUIZARTINIB4AURKB, NTRK2
CRIZOTINIB4AURKB, NTRK2
MIDOSTAURIN4AURKB, NTRK2
INAMRINONE4AURKB, PDE4B
CABOZANTINIB4AURKB
BENZYDAMINE4GUCY1A2
RUXOLITINIB4NTRK2
INFIGRATINIB PHOSPHATE4NTRK2
INFIGRATINIB4NTRK2
CERITINIB4NTRK2

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)4AURKB, GUCY1A2, NTRK2, PDE4B
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug4CNGB3, DUSP29, KCNJ13, PTPRT
DDruggable family + AlphaFold only, no drug5PKD1L1, SDK1, ADCY2, MFAP3L, OR8A1
EDifficult family or no structure, no drug16GIGYF2, TTC7B, ZFYVE19, TMEM106B, KNL1, RMDN3, DNAJC17, IQCE, TMEM132D, MYH15 (+6 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
RAD51124—
GIGYF25—
PKD1L10—
SDK10—
TTC7B0—
ZFYVE190—
CNGB30—
TMEM106B0—
ADCY231—
DUSP290—
KNL10—
RMDN30—
DNAJC170—
MFAP3L0—
IQCE0—
TMEM132D0—
MYH150—
EDIL30—
C15orf620—
GCHFR0—
CXCL10—
RAD51-AS10—
KCNJ139—
OR8A10—
PTPRT0—

Clinical trials & evidence

Clinical trials

Clinical trials: 4,026.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified650
PHASE2142
PHASE495
PHASE384
PHASE159
PHASE1/PHASE229
EARLY_PHASE123
PHASE2/PHASE318

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04221997PHASE4RECRUITINGTrial With the Treatment of Sertraline in Youth With Generalized, Separation and/or Social Anxiety Disorders.
NCT04245436PHASE4RECRUITINGAcute and Long-Term Antidepressant Treatment Success in Adolescents With Anxiety (AtLAS-A)
NCT04623099PHASE4RECRUITINGPharmacogenetically-guided Escitalopram Treatment for Pediatric Anxiety: Aiming to Improve Safety and Efficacy (PrEcISE)
NCT04751864PHASE4ACTIVE_NOT_RECRUITINGBrain Stimulation & Generalized Anxiety Study
NCT05934669PHASE4RECRUITINGIN Midazolam vs IN Dexmedetomidine vs IN Ketamine During Minimal Procedures in Pediatric ED
NCT06004115PHASE4RECRUITINGProcesses and Circuitry Underlying Threat Sensitivity as a Treatment Target for Co-morbid Anxiety and Depression
NCT06787976PHASE4NOT_YET_RECRUITINGEffect of Dolutegravir Compared With Darunavir/Cobicistat on the Severity of Neuropsychiatric Effects al 12 Weeks in Antirretroviral Treatment-Naive Adults.
NCT06843044PHASE4RECRUITINGEfficacy and Safety of Ranquilon in Patients With Anxiety Disorders Due to Neurasthenia and Adjustment Disorders
NCT07182890PHASE4RECRUITINGEfficacy of Clostridium Butyricum in Alleviating Anxiety and Depression in Patients With Functional Dyspepsia
NCT07187492PHASE4RECRUITINGEfficacy of Bacillus Coagulans in Alleviating Anxiety and Depression in Patients With Functional Dyspepsia
NCT07432815PHASE4RECRUITINGTreatment of Psoriasis With Depression and/or Anxiety With Methotrexate vs Combined Methotrexate and Antidepressant
NCT07439042PHASE4NOT_YET_RECRUITINGBuspirone for Anxiety in Autistic Youth
NCT07542730PHASE4NOT_YET_RECRUITINGDiphenhydramine as an Adjunct to Moderate Sedation for Procedural First Trimester Abortions
NCT00044642PHASE4COMPLETEDLorazepam-Induced Toxicity in the Aged
NCT00071630PHASE4COMPLETEDTherapeutic Processes and Treatment Outcome in Adolescents With Anxiety Disorders
NCT00105586PHASE4COMPLETEDDrug Therapy for Generalized Anxiety Disorder Among the Elderly
NCT00113295PHASE4COMPLETEDCombination of Paroxetine CR and Quetiapine for the Treatment of Refractory Generalized Anxiety Disorder
NCT00152776PHASE4COMPLETEDTreating Climacteric Symptoms With a Complex Homeopathic Remedy
NCT00174850PHASE4COMPLETEDSwitching From an SSRI to Tiagabine(GABITRIL) in Order to Alleviate SSRI Induced Sexual Dysfunction
NCT00182533PHASE4TERMINATEDSertraline in Generalized Social Phobia With Co-Occurring Anxiety and Mood Disorders
NCT00183274PHASE4COMPLETEDEffectiveness of Long-Term Versus Short-Term Treatment of Generalized Anxiety Disorder With Venlafaxine XR
NCT00208169PHASE4COMPLETEDAbilify Therapy for Reducing Comorbid Substance Abuse
NCT00302107PHASE4COMPLETEDA Placebo-Controlled Study of Mirtazapine for PTSD
NCT00352469PHASE4COMPLETEDTrial of Seroquel SR for Alcohol Dependence and Comorbid Anxiety
NCT00546923PHASE4COMPLETEDStudy Evaluating Venlafaxine Extended-Release in Depressed and Anxious Patients
NCT00596414PHASE4COMPLETEDSedation and Analgesia for Transjugular Liver Biopsy: A Randomized Double Blind Placebo Controlled Trial
NCT00623454PHASE4COMPLETEDNon Cardiac Chest Pain and Benign Palpitations
NCT00676364PHASE4COMPLETEDRandomized Control Trial of a Topical Anesthetic to Evaluate Pain and Anxiety During Venipuncture
NCT00703885PHASE4COMPLETEDPharmacofMRI (Functional Magnetic Resonance Imaging) of Anxiolytic Medications (Alprazolam)
NCT00706836PHASE4COMPLETEDPharmacofMRI of Anxiolytic Medications (Pregabalin)
NCT00721526PHASE4COMPLETEDDisulfiram Combined With Lorazepam for Alcohol Dependence and Anxiety Disorder
NCT00762099PHASE4UNKNOWNPerioperative Pregabalin Use, Rehabilitation, Pain Outcomes and Anxiety Following Hip Surgery
NCT00826111PHASE4COMPLETEDThe Effects of Eszopiclone and Lexapro on Prefrontal Glutamate and GABA in Depression With Anxiety and Insomnia
NCT00928772PHASE4TERMINATEDCranial Electro Therapy Stimulation in Reducing Perioperative Anxiety
NCT00951483PHASE4COMPLETEDCardiovascular Biomarkers and Quetiapine in Depression and Anxiety Patients
NCT01081249PHASE4COMPLETEDEffects of Oxytocin on Behavior and Physiology in a Psychotherapy Setting
NCT01148186PHASE4TERMINATEDAn Intervention Study to Reduce the Use and Impact of Potentially Inappropriate Medications Among Older Adults
NCT01155804PHASE4UNKNOWNAssessment of the Effectiveness of a Program of Preparation to Pregnancy and Delivery
NCT01285284PHASE4UNKNOWNEffect of Music Over the Tolerance to Colonoscopy.
NCT01309074PHASE4WITHDRAWNDoes Pregabalin Improve Symptoms of Anxiety in Patients With Epilepsy? A Comparison With Sertraline

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
ESCITALOPRAM424
FLUOXETINE421
PAROXETINE413
CITALOPRAM412
VENLAFAXINE412
ALPRAZOLAM410
BUSPIRONE410
HYDROXYZINE410
FLUVOXAMINE49
MIDAZOLAM48
LORAZEPAM47
PRAZOSIN46
PROPRANOLOL46
RISPERIDONE45
SERTRALINE45
MELATONIN44
MIRTAZAPINE44
TIAGABINE44
CANNABIDIOL43
DIAZEPAM43
DULOXETINE HYDROCHLORIDE43
VORTIOXETINE43
ZOPICLONE43
ACAMPROSATE42
CLOBAZAM42
CYCLOSERINE42
DIPHENHYDRAMINE42
HALOPERIDOL42
KETAMINE42
MIFEPRISTONE42

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_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot