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Atlas / Disease / Psychotic disorder

Psychotic disorder

disease
On this page

Also known as mental or behavioral disordermental or behavioural disorderpsychosis

Summary

Psychotic disorder (MONDO:0005485) is a disease (an umbrella term covering 8 Mondo subtypes) with 18 cohort genes (54 GWAS associations across 23 studies) and 668 clinical trials. Top therapeutic interventions include ziprasidone, olanzapine, and aripiprazole.

At a glance

  • Umbrella term: 8 Mondo subtypes
  • Cohort genes: 18
  • GWAS associations: 54
  • ClinVar variants: 4
  • Clinical trials: 668

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namepsychotic disorder
Mondo IDMONDO:0005485
EFOEFO:0005407
DOIDDOID:2468
NCITC78576
SNOMED CT69322001
UMLSC0033975
MedGen19568
Is cancer (heuristic)no

Also known as: mental or behavioral disorder · mental or behavioural disorder · psychosis

Data availability: 4 ClinVar variants · 54 GWAS associations (23 studies) · 1 HPO phenotype · 3 cell lines.

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › cognitive disorder › psychotic disorder

Related subtypes (5): amnestic disorder, dementia, alexia, delirium, subjective cognitive decline

Subtypes (8): schizophreniform disorder, alcoholic psychosis, delusional disorder, substance-induced psychosis, schizophrenia, methamphetamine-induced psychosis, schizoaffective disorder, postpartum psychosis

Genetics & variants

GWAS landscape

54 GWAS associations across 23 studies. Top hits map to 29 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs95199281e-07LINC00343 - RNA5SP38?
rs2459142e-07CHN2, CPVL?
rs121968602e-07COL21A1?
chr3:38318332e-07A0.67
rs351885062e-07ZNF462 - RAD23BA0.86
rs168985613e-07FBXO32 - RN7SKP155A0.76
rs4293583e-07APOET0.83
rs1123688303e-07RBM34, ARID4BT1.39
rs121054215e-07TMEM182?
rs7801165705e-07NDUFB6 - TAF1LCT0.19
chr11:1189175876e-07T1.31
rs356691946e-07GCNT3G0.78
rs8369897e-07FTO - LINC02169T0.88
rs19595368e-07TRIM9?
rs19293888e-07CAMK1DT0.89
rs558238078e-07FLJ36000 - MTND6P35T0.86
rs1872933859e-07SCGB1D5P - NOL8P1A1.54
rs60815411e-06SLC24A3?
rs60507901e-06ZNF337A0.87
rs46198072e-06RPL24P7 - UBE2E2-DT?
rs107392402e-06RAD23B - LINC01509A1.12
rs72830762e-06C21orf91-OT1C0.88
rs169024603e-06PVT1?
rs15725913e-06NALCN?
rs1837480763e-06ANO3A1.38
rs357920583e-06KIF26BA1.13
rs60512723e-06MIR663AHG - FRG1CPT1.14
rs67175683e-06LINC02580C1.12
rs727691383e-06LINC00923T0.8
rs795717573e-06MT3 - MT2AT1.18

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90481723Verma A202416,732423,587Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481722Verma A202411,580106,379Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481733Verma A20249,712432,125Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481732Verma A20247,094110,965Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90708782Antonsdottir IM20243,9616,027Genetic associations with psychosis and affective disturbance in Alzheimer’s disease.
GCST90481720Verma A20243,37254,908Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90708784Antonsdottir IM20242,7783,199Genetic associations with psychosis and affective disturbance in Alzheimer’s disease.
GCST90481730Verma A20242,18056,282Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST008910Trochet H20191,78723,008Bayesian meta-analysis across genome-wide association studies of diverse phenotypes.
GCST90435853Zhou W2018850365,476Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding1
Tier 2: splice/UTR0
Tier 3: regulatory3
Tier 4: intronic/intergenic46

MAF distribution

BucketVariants
common (>=0.05)44
low_freq (0.01-0.05)0
rare (<0.01)0
unknown6

Functional consequences

ConsequenceCount
intron_variant23
intergenic_variant17
unknown4
regulatory_region_variant3
non_coding_transcript_exon_variant2
missense_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs951992813106052437C>A,G0.05intron_variantLINC00343 - RNA5SP381e-07Tier 4: intronic/intergenic
rs245914729178543G>A,T0.05regulatory_region_variantCHN2, CPVL2e-07Tier 3: regulatory
rs12196860656085576G>A0.05intron_variantCOL21A12e-07Tier 4: intronic/intergenic
chr3:38318332e-07Tier 4: intronic/intergenic
rs351885069107244562G>A0.05intron_variantZNF462 - RAD23B2e-07Tier 4: intronic/intergenic
rs168985618123553071A>G,T0.05regulatory_region_variantFBXO32 - RN7SKP1553e-07Tier 3: regulatory
rs4293581944908684T>C0.05missense_variantAPOE3e-07Tier 1: coding
rs1123688301235155396T>C0.05intron_variantRBM34, ARID4B3e-07Tier 4: intronic/intergenic
rs121054212102959630C>T0.05intergenic_variantTMEM1825e-07Tier 4: intronic/intergenic
rs780116570932594703intergenic_variantNDUFB6 - TAF1L5e-07Tier 4: intronic/intergenic
chr11:1189175876e-07Tier 4: intronic/intergenic
rs356691941559628924GTTTTT>G,GTT,GTTT,GTTTT,GTTTTTT,GTTTTTTT,GTTTTTTTT,GTTTTTTTTT,GTTTTTTTTTT,GTTTTTTTTTTT,GTTTTTTTTTTTT,GTTTTTTTTTTTTT,GTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT0.05intergenic_variantGCNT36e-07Tier 4: intronic/intergenic
rs8369891654204289G>T0.05intergenic_variantFTO - LINC021697e-07Tier 4: intronic/intergenic
rs19595361450980053T>A,C,G0.05intron_variantTRIM98e-07Tier 4: intronic/intergenic
rs19293881012794602T>A,C0.05intron_variantCAMK1D8e-07Tier 4: intronic/intergenic
rs558238071722460404C>G,T0.05intron_variantFLJ36000 - MTND6P358e-07Tier 4: intronic/intergenic
rs1872933854165544432G>A,T0.05intergenic_variantSCGB1D5P - NOL8P19e-07Tier 4: intronic/intergenic
rs60815412019232246A>G0.05intron_variantSLC24A31e-06Tier 4: intronic/intergenic
rs60507902025691705A>G0.05intron_variantZNF3371e-06Tier 4: intronic/intergenic
rs4619807323152437G>A0.05intergenic_variantRPL24P7 - UBE2E2-DT2e-06Tier 4: intronic/intergenic
rs107392409107346412G>A0.05intergenic_variantRAD23B - LINC015092e-06Tier 4: intronic/intergenic
rs72830762117770827C>G,T0.05intron_variantC21orf91-OT12e-06Tier 4: intronic/intergenic
rs169024608127907951G>A,C0.05intron_variantPVT13e-06Tier 4: intronic/intergenic
rs157259113101407725C>A,G,T0.05intron_variantNALCN3e-06Tier 4: intronic/intergenic
rs1837480761126508785T>A0.05intron_variantANO33e-06Tier 4: intronic/intergenic
rs357920581245670493AT>A,ATT,ATTT0.05intron_variantKIF26B3e-06Tier 4: intronic/intergenic
rs60512722026293225C>T0.05intergenic_variantMIR663AHG - FRG1CP3e-06Tier 4: intronic/intergenic
rs6717568243080607G>C,T0.05regulatory_region_variantLINC025803e-06Tier 3: regulatory
rs727691381597792711C>T0.05intron_variantLINC009233e-06Tier 4: intronic/intergenic
rs795717571656604999T>C0.05intergenic_variantMT3 - MT2A3e-06Tier 4: intronic/intergenic

ClinVar germline variants

4 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 uncertain significance

ClinVarVariant (HGVS)GeneClassificationReview
26803946;XY;t(3;18)(q13.31;q22.1)dnPathogeniccriteria provided, single submitter
995853NM_005772.5(RCL1):c.370C>T (p.Gln124Ter)RCL1Pathogenicno assertion criteria provided
397528NC_000022.11:g.50721470dupSHANK3Pathogeniccriteria provided, multiple submitters, no conflicts
995854GRCh37/hg19 2q13(chr2:110862474-110983457)x1BUB1Uncertain significanceno assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
BUB1Orphanet:1052Mosaic variegated aneuploidy syndrome
SHANK3Orphanet:662169Phelan-McDermid syndrome due to 22q13.3 deletion
SHANK3Orphanet:662172Phelan-McDermid syndrome due to SHANK3 mutation
NALCNOrphanet:1146Distal arthrogryposis type 1
NALCNOrphanet:1147Sheldon-Hall syndrome
NALCNOrphanet:2053Freeman-Sheldon syndrome
NALCNOrphanet:562528Congenital limbs-face contractures-hypotonia-developmental delay syndrome
NALCNOrphanet:700336Hypotonia-speech impairment-severe cognitive delay syndrome due to NALCN deficiency
PYGLOrphanet:369Glycogen storage disease due to liver glycogen phosphorylase deficiency
RASGRP1Orphanet:664699EBV-induced lymphoproliferative disease due to RASGRP1 deficiency

Cohort genes → proteins

18 cohort genes, 16 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only15
multi_evidence3

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SLC24A3HGNC:10977ENSG00000185052Q9HC58Sodium/potassium/calcium exchanger 3gwas
BUB1HGNC:1148ENSG00000169679O43683Mitotic checkpoint serine/threonine-protein kinase BUB1clinvar
TNFHGNC:11892ENSG00000232810P01375Tumor necrosis factorgwas
UBE2E2HGNC:12478ENSG00000182247Q96LR5Ubiquitin-conjugating enzyme E2 E2gwas
SHANK3HGNC:14294ENSG00000251322Q9BYB0SH3 and multiple ankyrin repeat domains protein 3clinvar
CPVLHGNC:14399ENSG00000106066Q9H3G5Probable serine carboxypeptidase CPVLgwas
TRIM9HGNC:16288ENSG00000100505Q9C026E3 ubiquitin-protein ligase TRIM9gwas
COL21A1HGNC:17025ENSG00000124749Q96P44Collagen alpha-1(XXI) chaingwas
RCL1HGNC:17687ENSG00000120158Q9Y2P8RNA 3’-terminal phosphate cyclase-like proteinclinvar
NALCNHGNC:19082ENSG00000102452Q8IZF0Sodium leak channel NALCNgwas
CHN2HGNC:1944ENSG00000106069P52757Beta-chimaeringwas
FAM98BHGNC:26773ENSG00000171262Q52LJ0tRNA-splicing ligase complex subunit FAM98Bgwas
RPL24P7HGNC:36862ENSG00000215016RPL24 pseudogene 7gwas
ITGBL1HGNC:6164ENSG00000198542O95965Integrin beta-like protein 1gwas
MICBHGNC:7091ENSG00000204516Q29980MHC class I polypeptide-related sequence Bgwas
PVT1HGNC:9709ENSG00000249859Pvt1 oncogenegwas
PYGLHGNC:9725ENSG00000100504P06737Glycogen phosphorylase, liver formgwas
RASGRP1HGNC:9878ENSG00000172575O95267RAS guanyl-releasing protein 1gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SLC24A3Sodium/potassium/calcium exchanger 3Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+).
BUB1Mitotic checkpoint serine/threonine-protein kinase BUB1Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment.
TNFTumor necrosis factorCytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR.
UBE2E2Ubiquitin-conjugating enzyme E2 E2Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins.
SHANK3SH3 and multiple ankyrin repeat domains protein 3Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance.
CPVLProbable serine carboxypeptidase CPVLMay be involved in the digestion of phagocytosed particles in the lysosome, participation in an inflammatory protease cascade, and trimming of peptides for antigen presentation.
TRIM9E3 ubiquitin-protein ligase TRIM9E3 ubiquitin-protein ligase which ubiquitinates itself in cooperation with an E2 enzyme UBE2D2/UBC4 and serves as a targeting signal for proteasomal degradation.
RCL1RNA 3’-terminal phosphate cyclase-like proteinAs part of the small subunit (SSU) processome, it plays a role in 40S-ribosomal-subunit biogenesis in the early pre-rRNA processing steps at sites A0, A1 and A2 that are required for proper maturation of the 18S RNA.
NALCNSodium leak channel NALCNVoltage-gated ion channel responsible for the resting Na(+) permeability that controls neuronal excitability.
CHN2Beta-chimaerinGTPase-activating protein for p21-rac.
FAM98BtRNA-splicing ligase complex subunit FAM98BAccessory subunit of the tRNA-splicing ligase complex that acts by directly joining spliced tRNA halves to mature-sized tRNAs by incorporating the precursor-derived splice junction phosphate into the mature tRNA as a canonical 3’,5’-phosph…
MICBMHC class I polypeptide-related sequence BWidely expressed membrane-bound protein which acts as a ligand to stimulate an activating receptor KLRK1/NKG2D, expressed on the surface of essentially all human natural killer (NK), gammadelta T and CD8+ alphabeta T-cells.
PYGLGlycogen phosphorylase, liver formAllosteric enzyme that catalyzes the rate-limiting step in glycogen catabolism, the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate, and plays a central role in maintaining cellular and organismal glucose homeostasis.
RASGRP1RAS guanyl-releasing protein 1Functions as a calcium- and diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP.

Protein-family classification

Druggable: 6 · Difficult: 3 · Unknown: 9 · Druggable fraction: 0.33

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

FamilyGenesFoldFDR
Ion channel16.2×0.645
Protease12.0×0.645
Scaffold/PPI21.9×0.645
Antibody/Immunoglobulin11.6×0.645
Kinase11.5×0.645
Enzyme (other)21.3×0.645
Other/Unknown90.9×0.879
Transcription factor10.5×0.902

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SLC24A3Other/UnknownnoK/Na/Ca-exchanger, NaCa_Exmemb, NCX_ion-bd_dom_sf
BUB1Kinaseyes2.7.11.1Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TNFOther/UnknownnoTNF_alpha, TNF_dom, TNF
UBE2E2Enzyme (other)yes2.3.2.23UBC, UBQ-conjugating_enzyme/RWD, UBQ-conjugating_AS
SHANK3Scaffold/PPInoSH3_domain, PDZ, SAM
CPVLProteaseyesPeptidase_S10, Ser_caboxypep_ser_AS, AB_hydrolase_fold
TRIM9Transcription factornoZnf_B-box, Znf_RING, B30.2/SPRY
COL21A1Other/UnknownnoVWF_A, Collagen, ConA-like_dom_sf
RCL1Other/UnknownnoRNA3’_term_phos_cyc, RNA3’-term_phos_cycl_insert, RNA3’P_cycl/enolpyr_Trfase_a/b
NALCNIon channelyesIon_trans_dom, Volt_channel_dom_sf, NALCN
CHN2Scaffold/PPInoRhoGAP_dom, SH2, PKC_DAG/PE
FAM98BOther/UnknownnoFAM98
RPL24P7Other/Unknownno
ITGBL1Other/UnknownnoEGF, EGF_extracell, Integrin_bsu
MICBAntibody/ImmunoglobulinyesIg_C1-set, Ig-like_dom, MHC_I-like_Ag-recog
PVT1Other/Unknownno
PYGLEnzyme (other)yes2.4.1.1Glyco_trans_35, Glycg_phsphrylas, Pyridoxal_P_attach_site
RASGRP1Other/UnknownnoRas-like_Gua-exchang_fac_N, RASGEF_cat_dom, EF_hand_dom

Expression context

Cohort genes with no expression data: 0.

17 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)18
unknown0

Top tissues across cohort

TissueCohort genes
cerebellar cortex3
cerebellar hemisphere3
monocyte3
ganglionic eminence2
granulocyte2
sural nerve2
right hemisphere of cerebellum2
leukocyte2
mononuclear cell2
Brodmann (1909) area 232
cerebellar vermis2
lateral nuclear group of thalamus1
saphenous vein1
tongue squamous epithelium1
primordial germ cell in gonad1
ventricular zone1
bone marrow1
male germ line stem cell (sensu Vertebrata) in testis1
oviduct epithelium1
prefrontal cortex1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SLC24A3272broadmarkerlateral nuclear group of thalamus, tongue squamous epithelium, saphenous vein
BUB1185ubiquitousmarkerventricular zone, primordial germ cell in gonad, ganglionic eminence
TNF119broadmarkergranulocyte, male germ line stem cell (sensu Vertebrata) in testis, bone marrow
UBE2E2255ubiquitousmarkersural nerve, oviduct epithelium, prefrontal cortex
SHANK3246ubiquitousmarkerright hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
CPVL264ubiquitousmarkermonocyte, mononuclear cell, leukocyte
TRIM9215broadmarkerright hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
COL21A1239broadmarkerblood vessel layer, bronchial epithelial cell, sural nerve
RCL1240ubiquitousmarkerbuccal mucosa cell, right lobe of liver, liver
NALCN201ubiquitousmarkermiddle temporal gyrus, Brodmann (1909) area 23, corpus callosum
CHN2139broadmarkercerebellum, cerebellar cortex, cerebellar hemisphere
FAM98B255ubiquitousmarkerupper arm skin, left ventricle myocardium, cerebellar vermis
RPL24P758markerganglionic eminence, apex of heart, mucosa of stomach
ITGBL1243broadmarkerfrontal pole, paraflocculus, middle frontal gyrus
MICB133ubiquitousyesgranulocyte, leukocyte, monocyte
PVT1227ubiquitousmarkerlower esophagus mucosa, adrenal tissue, colonic epithelium
PYGL255ubiquitousmarkerblood, monocyte, mononuclear cell
RASGRP1248broadmarkerpons, cerebellar vermis, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

SymbolInteractor count
TNF11,116
SHANK33,702
BUB13,618
CPVL3,307
UBE2E23,079
PYGL2,733
RCL12,272
TRIM92,141
RASGRP11,939
NALCN1,860

Intra-cohort edges

ABSources
CHN2CPVLstring_interaction
COL21A1ITGBL1string_interaction
ITGBL1SHANK3intact

Structural data

PDB: 11 · AlphaFold-only: 5 · No structure: 2

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
TNFP0137552
PYGLP0673719
UBE2E2Q96LR510
BUB1O436839
NALCNQ8IZF05
SHANK3Q9BYB03
RCL1Q9Y2P83
TRIM9Q9C0262
MICBQ299802
RASGRP1O952672
CHN2P527571

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
CPVLQ9H3G593.55
ITGBL1O9596584.28
FAM98BQ52LJ075.11
SLC24A3Q9HC5870.31
COL21A1Q96P4468.41

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 57. Enrichment computed across 18 evidence-associated genes (14 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 14 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Activation of RAS in B cells1163.1×0.158RASGRP1
TNFR1-mediated ceramide production1135.9×0.158TNF
RUNX2 regulates genes involved in cell migration1102.0×0.158ITGBL1
Sodium/Calcium exchangers174.2×0.158SLC24A3
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)162.8×0.158TNF
Glycogen breakdown (glycogenolysis)154.4×0.158PYGL
Rap1 signalling151.0×0.158RASGRP1
Effects of PIP2 hydrolysis132.6×0.169RASGRP1
TNFR1-induced proapoptotic signaling131.4×0.169TNF
Integrin signaling130.2×0.169RASGRP1
TNF signaling130.2×0.169TNF
TNFR1-induced NF-kappa-B signaling pathway124.0×0.194TNF
Collagen chain trimerization118.5×0.202COL21A1
Transcriptional regulation by RUNX2118.1×0.202ITGBL1
Interleukin-10 signaling116.6×0.202TNF
Regulation of TNFR1 signaling116.0×0.202TNF
Amplification of signal from the kinetochores114.1×0.202BUB1
tRNA processing in the nucleus114.1×0.202FAM98B
rRNA modification in the nucleus and cytosol113.4×0.202RCL1
TNFR2 non-canonical NF-kB pathway112.9×0.202TNF
Antigen processing: Ubiquitination & Proteasome degradation25.3×0.202UBE2E2, TRIM9
Collagen biosynthesis and modifying enzymes112.2×0.204COL21A1
Mitotic Spindle Checkpoint111.3×0.204BUB1
FCERI mediated NF-kB activation111.2×0.204RASGRP1
Stimuli-sensing channels19.7×0.213NALCN
Transcriptional regulation of white adipocyte differentiation19.3×0.213TNF
R-HSA-42539319.3×0.213SLC24A3
Transport of small molecules23.6×0.213SLC24A3, NALCN
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal18.3×0.224BUB1
Interleukin-4 and Interleukin-13 signaling17.3×0.232TNF

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 15 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
regulation of sister chromatid cohesion11123.5×0.023BUB1
positive regulation of translational initiation by iron11123.5×0.023TNF
negative regulation of branching involved in lung morphogenesis11123.5×0.023TNF
negative regulation of bile acid secretion11123.5×0.023TNF
response to Gram-negative bacterium11123.5×0.023TNF
positive regulation of interleukin-33 production11123.5×0.023TNF
response to 3,3’,5-triiodo-L-thyronine11123.5×0.023TNF
positive regulation of maintenance of mitotic sister chromatid cohesion, centromeric11123.5×0.023BUB1
negative regulation of L-glutamate import across plasma membrane1561.7×0.023TNF
chronic inflammatory response to antigenic stimulus1561.7×0.023TNF
positive regulation of chronic inflammatory response to antigenic stimulus1561.7×0.023TNF
positive regulation of fractalkine production1561.7×0.023TNF
positive regulation of protein transport1561.7×0.023TNF
positive regulation of vitamin D biosynthetic process1561.7×0.023TNF
guanylate kinase-associated protein clustering1561.7×0.023SHANK3
response to hydrogen sulfide1561.7×0.023TNF
response to quercetin1561.7×0.023TNF
response to gold nanoparticle1561.7×0.023TNF
positive regulation of blood microparticle formation1561.7×0.023TNF
regulation of endothelial cell apoptotic process1561.7×0.023TNF
positive regulation of MAP kinase activity286.4×0.023TNF, RASGRP1
positive regulation of protein phosphorylation236.8×0.023TNF, RASGRP1
immune response-activating cell surface receptor signaling pathway1374.5×0.024MICB
secretory granule localization1374.5×0.024RASGRP1
positive regulation of synapse structural plasticity1374.5×0.024SHANK3
regulation of branching involved in salivary gland morphogenesis1374.5×0.024TNF
positive regulation of synoviocyte proliferation1374.5×0.024TNF
positive regulation of neutrophil activation1374.5×0.024TNF
obsolete regulation of membrane lipid metabolic process1374.5×0.024TNF
endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)1280.9×0.024RCL1

Therapeutics

Drugs indicated for this disease

44 approved, 17 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
AcetophenazineApproved (phase 4)
AmisulprideApproved (phase 4)
AripiprazoleApproved (phase 4)
AsenapineApproved (phase 4)
BenperidolApproved (phase 4)
BrexpiprazoleApproved (phase 4)
BromperidolApproved (phase 4)
CariprazineApproved (phase 4)
ChlorpromazineApproved (phase 4)
ChlorprothixeneApproved (phase 4)
ClozapineApproved (phase 4)
DroperidolApproved (phase 4)
FluphenazineApproved (phase 4)
FluspirileneApproved (phase 4)
HaloperidolApproved (phase 4)
IloperidoneApproved (phase 4)
LevomepromazineApproved (phase 4)
LoxapineApproved (phase 4)
LumateperoneApproved (phase 4)
MesoridazineApproved (phase 4)
MolindoneApproved (phase 4)
OlanzapineApproved (phase 4)
OxypertineApproved (phase 4)
PaliperidoneApproved (phase 4)
PericiazineApproved (phase 4)
PerphenazineApproved (phase 4)
PimavanserinApproved (phase 4)
PimozideApproved (phase 4)
Pipotiazine PalmitateApproved (phase 4)
ProchlorperazineApproved (phase 4)
PromazineApproved (phase 4)
ProthipendylApproved (phase 4)
QuetiapineApproved (phase 4)
RemoxiprideApproved (phase 4)
RisperidoneApproved (phase 4)
SertindoleApproved (phase 4)
SulpirideApproved (phase 4)
ThioridazineApproved (phase 4)
ThiothixeneApproved (phase 4)
TrifluoperazineApproved (phase 4)
TrifluperidolApproved (phase 4)
TriflupromazineApproved (phase 4)
VeraliprideApproved (phase 4)
ZiprasidoneApproved (phase 4)
AcetylcysteinePhase 3 (in late-stage trials)
AspirinPhase 3 (in late-stage trials)
CannabidiolPhase 3 (in late-stage trials)
CyanocobalaminPhase 3 (in late-stage trials)
DoconexentPhase 3 (in late-stage trials)
FlupentixolPhase 3 (in late-stage trials)
IcosapentPhase 3 (in late-stage trials)
LithiumPhase 3 (in late-stage trials)
LurasidonePhase 3 (in late-stage trials)
MelperonePhase 3 (in late-stage trials)
MinocyclinePhase 3 (in late-stage trials)
NiacinPhase 3 (in late-stage trials)
PerazinePhase 3 (in late-stage trials)
PipamperonePhase 3 (in late-stage trials)
SulforaphanePhase 3 (in late-stage trials)
TiapridePhase 3 (in late-stage trials)
ZuclopenthixolPhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Folic Acid, Levetiracetam, Memantine, Metyrosine, OMEGA-3-ACID ETHYL ESTERS, Pantoprazole, Pyridoxine, Rituximab, Sodium Benzoate.

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 15

Druggability breadth: 5 of 18 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
BUB1GILTERITINIB
TNFPREDNISOLONE

Top cohort targets by molecule count

SymbolMoleculesMax phase
TNF124
BUB1104
PYGL33
SLC24A300
UBE2E200
SHANK300
CPVL00
TRIM900
COL21A100
RCL100

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
GILTERITINIB4BUB1
SUNITINIB4BUB1
ERLOTINIB4BUB1
PREDNISOLONE4TNF
POMALIDOMIDE4TNF
PENTOXIFYLLINE4TNF
MESALAMINE4TNF
LENALIDOMIDE4TNF
LOSMAPIMOD3BUB1
ICOTINIB3BUB1
MARIMASTAT3TNF
IBERDOMIDE3TNF
ALVOCIDIB3PYGL
QUERCETIN3PYGL
AT-92832BUB1
MILCICLIB2BUB1
DORAMAPIMOD2TNF
AVADOMIDE2TNF
MIZACORAT2TNF
LINPERLISIB2TNF
ROLIPRAM2TNF
AFEGOSTAT2PYGL
XL-0191BUB1
CYC-1161BUB1
CUDC-1011BUB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

SymbolAssaysType breakdown
TNF193Binding:162, Functional:31
BUB186Binding:84, Functional:2
PYGL58Binding:58
RASGRP18Binding:8
CHN21Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
BUB12.7.11.1non-specific serine/threonine protein kinase
UBE2E22.3.2.23, 2.3.2.24E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme
PYGL2.4.1.1glycogen phosphorylase

Cohort genes with high screening signal

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

SymbolChEMBL assays
TNF193

Pharmacogenomics

Cohort genes with a PharmGKB record: 17; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

25 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)
GILTERITINIB4BUB1
SUNITINIB4BUB1
ERLOTINIB4BUB1
PREDNISOLONE4TNF
POMALIDOMIDE4TNF
PENTOXIFYLLINE4TNF
MESALAMINE4TNF
LENALIDOMIDE4TNF
LOSMAPIMOD3BUB1
ICOTINIB3BUB1
MARIMASTAT3TNF
IBERDOMIDE3TNF
ALVOCIDIB3PYGL
QUERCETIN3PYGL
AT-92832BUB1
MILCICLIB2BUB1
DORAMAPIMOD2TNF
AVADOMIDE2TNF
MIZACORAT2TNF
LINPERLISIB2TNF
ROLIPRAM2TNF
AFEGOSTAT2PYGL
XL-0191BUB1
CYC-1161BUB1
CUDC-1011BUB1

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)2BUB1, TNF
BPhased (≥1) drug, not yet approved1PYGL
CDruggable family + PDB, no drug3UBE2E2, NALCN, MICB
DDruggable family + AlphaFold only, no drug1CPVL
EDifficult family or no structure, no drug11SLC24A3, SHANK3, TRIM9, COL21A1, RCL1, CHN2, FAM98B, RPL24P7, ITGBL1, PVT1 (+1 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
SLC24A30—
UBE2E20—
SHANK30—
CPVL0—
TRIM90—
COL21A10—
RCL10—
NALCN0—
CHN21—
FAM98B0—
RPL24P70—
ITGBL10—
MICB0—
PVT10—
RASGRP18—

Clinical trials & evidence

Clinical trials

Clinical trials: 668.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified491
PHASE453
PHASE340
PHASE238
PHASE125
EARLY_PHASE112
PHASE2/PHASE35
PHASE1/PHASE24

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05282277PHASE4RECRUITINGExamining the Effects of Estradiol on Neural and Molecular Response to Reward
NCT05316883PHASE4RECRUITINGBiomarkers in Clozapine-responding Schizophrenia
NCT06546475PHASE4NOT_YET_RECRUITINGA Pilot Trial of Tapering Antipsychotics for Patients in Remitted Psychosis Co-administering With N-Acetylcysteine
NCT06590298PHASE4NOT_YET_RECRUITINGEvaluating the Effects of Adjunctive Aripiprazole on Weight and Metabolic Outcomes in Females
NCT06634641PHASE4RECRUITINGClozapine-related Immunodeficiency in Parkinsons Disease
NCT07001878PHASE4RECRUITINGCannabis Potency Effects on Brain White Matter in Early Phase Psychosis
NCT00001656PHASE4COMPLETEDComparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00009217PHASE4COMPLETEDTreatment of Behavioral Symptoms in Alzheimer’s Disease
NCT00044187PHASE4COMPLETEDThe Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00108368PHASE4COMPLETEDThe Effects of Risperidone and Olanzapine on Thinking
NCT00130923PHASE4COMPLETEDRisperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020PHASE4COMPLETEDClinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00156715PHASE4COMPLETEDEfficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223PHASE4COMPLETEDEffectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00169026PHASE4TERMINATEDAlcoholism and Schizophrenia: Effects of Clozapine
NCT00199940PHASE4COMPLETEDSafety And Efficacy Study Of Ziprasidone In Pediatric Psychotic Illness
NCT00202306PHASE4COMPLETEDIndicated Prevention of Psychotic Disorders With Low-dose Lithium
NCT00216632PHASE4COMPLETEDA Study of Treatment Success in Changing From Olanzapine to Long-acting Injectable Risperidone (RISPERDAL® CONSTA™)
NCT00224302PHASE4COMPLETEDTreatment of MDEs During the Course of Psychotic Disorders With Duloxetine
NCT00232349PHASE4TERMINATEDEfficacy of Galantamine to Treat Schizophrenia
NCT00246259PHASE4COMPLETEDA Trial Comparing Risperidone Long-Acting Injection With Oral Antipsychotic in the Treatment of Early Psychosis
NCT00249171PHASE4COMPLETEDA Study of Risperidone in Combination With Lorazepam Compared With Standard Therapy for Emergency Treatment of Schizophrenic Patients
NCT00272597PHASE4COMPLETEDRisperidone LA Heathcare Resource Study
NCT00282165PHASE4TERMINATEDEfficacy of a Triptan in the Treatment of Hostility and Aggression Among Convicts With a Psychiatric Treatment Order
NCT00299702PHASE4COMPLETEDEvaluation of Effectiveness of Risperdal® Consta® Compared to Abilify® Over a Two-year Period in Patients With Schizophrenia
NCT00307203PHASE4COMPLETEDSafety and Effectiveness of Sustained Release Bupropion in Treating Individuals With Schizophrenia Who Smoke
NCT00369239PHASE4COMPLETEDTreatment With Risperidone Long Acting Injectable (RLAI) in an Early Phase of Psychosis
NCT00417482PHASE4COMPLETEDAntipsychotic Discontinuation in Alzheimer’s Disease
NCT00498550PHASE4COMPLETEDTreatment of Schizophrenia and Comorbid Cannabis Use Disorder: Comparing Clozapine to Treatment-as-Usual
NCT00535145PHASE4COMPLETEDStudy to Measure the Safety of Paliperidone ER (Extended-release) in Patients With Liver Disease
NCT00702793PHASE4WITHDRAWNSafety and Tolerability of Varenicline in Schizophrenia (SATOVA)
NCT00786318PHASE4WITHDRAWNZiprasidone vs Standard Therapy for Agitated Patients in the ED
NCT00806234PHASE4COMPLETEDReducing Weight Gain and Improving Metabolic Function in Children Being Treated With Antipsychotics
NCT00932529PHASE4COMPLETEDUse, Effects and Side-effects of Second-generation Antipsychotics in a Naturalistic Setting
NCT00986167PHASE4UNKNOWNQuetiapine Extended Release (XR) for the Management of Psychotic Aggression or Agitation in Adult Acute Psychiatry
NCT01015586PHASE4COMPLETEDTreatment of Alcohol Dependence and Comorbid Bipolar Disorder
NCT01119014PHASE4COMPLETEDTolerance and Effect of Antipsychotics in Children and Adolescents With Psychosis
NCT01119638PHASE4COMPLETEDEscitalopram Treatment for BPSD in Alzheimer’s Disease in Comparison to Risperidone
NCT01161277PHASE4COMPLETEDEffects of Aripiprazole and Haloperidol on Mesolimbic System Functioning
NCT01279213PHASE4COMPLETEDClozapine/Paliperidone Versus Clozapine/Placebo in Resistant Schizophrenia

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
ZIPRASIDONE427
OLANZAPINE415
ARIPIPRAZOLE49
CLOZAPINE48
QUETIAPINE48
RISPERIDONE48
FLUOXETINE46
MIFEPRISTONE45
AMISULPRIDE43
HALOPERIDOL43
PALIPERIDONE43
CANNABIDIOL42
DRONABINOL42
GLYCINE42
PANTOPRAZOLE42
PIMOZIDE42
VALACYCLOVIR42
VARENICLINE42
ACETYLCYSTEINE41
AMANTADINE41
ASENAPINE41
BENZTROPINE41
BREXPIPRAZOLE41
CEFTRIAXONE41
DEXTROAMPHETAMINE SULFATE41
DIVALPROEX SODIUM41
DULOXETINE41
ESCITALOPRAM41
ESTRADIOL41
GALANTAMINE41

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