Childhood-onset schizophrenia
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Summary
Childhood-onset schizophrenia (MONDO:0957430) is a disease with 20 cohort genes.
At a glance
- Prevalence: Unknown (Europe) [Orphanet-validated]
- Cohort genes: 20
- ClinVar variants: 21
Clinical features
Epidemiology
Prevalence records
1 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Annual incidence | 1-5 / 10 000 | Europe | Validated |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | childhood-onset schizophrenia |
| Mondo ID | MONDO:0957430 |
| Orphanet | 641496 |
| UMLS | C0036346 |
| MedGen | 48576 |
| GARD | 0004766 |
| Is cancer (heuristic) | no |
Data availability: 21 ClinVar variants.
Disease family
Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › cognitive disorder › psychotic disorder › schizophrenia › childhood-onset schizophrenia
Related subtypes (17): paranoid schizophrenia, treatment-refractory schizophrenia, schizophrenia 1, schizophrenia 3, schizophrenia 5, schizophrenia 7, schizophrenia 8, schizophrenia 2, schizophrenia 10, schizophrenia 11, schizophrenia 12, schizophrenia 15, schizophrenia 16, chromosome 2p16.3 deletion syndrome, early-onset schizophrenia, schizophrenia 19, schizophrenia 17
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
21 retrieved; paginated sample, class counts are floors:
16 likely pathogenic, 3 benign, 2 conflicting classifications of pathogenicity
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 208393 | NM_001040025.3(ARL16):c.-41G>T | ARL16 | Likely pathogenic | criteria provided, single submitter |
| 208399 | NM_138706.5(B3GNT6):c.552C>G (p.Asp184Glu) | B3GNT6 | Likely pathogenic | criteria provided, single submitter |
| 208382 | NM_207361.6(FREM2):c.8351G>A (p.Arg2784Lys) | FREM2 | Likely pathogenic | criteria provided, single submitter |
| 208386 | NM_003774.5(GALNT4):c.1194C>T (p.Asn398=) | GALNT4 | Likely pathogenic | criteria provided, single submitter |
| 208391 | NM_207370.4(GPR153):c.217C>T (p.Arg73Cys) | GPR153 | Likely pathogenic | criteria provided, single submitter |
| 208388 | NM_005685.4(GTF2IRD1):c.973C>T (p.Arg325Cys) | GTF2IRD1 | Likely pathogenic | criteria provided, single submitter |
| 208387 | NM_000210.4(ITGA6):c.*91AGA[1] | ITGA6 | Likely pathogenic | criteria provided, single submitter |
| 208394 | NM_002402.4(MEST):c.559C>T (p.Pro187Ser) | MEST | Likely pathogenic | criteria provided, single submitter |
| 208395 | NM_015009.3(PDZRN3):c.820G>A (p.Asp274Asn) | PDZRN3 | Likely pathogenic | criteria provided, single submitter |
| 208402 | NM_000961.4(PTGIS):c.824G>A (p.Arg275Gln) | PTGIS | Likely pathogenic | criteria provided, single submitter |
| 208401 | NM_021975.4(RELA):c.329T>C (p.Ile110Thr) | RELA | Likely pathogenic | criteria provided, single submitter |
| 208396 | NM_001035.3(RYR2):c.2236C>T (p.Gln746Ter) | RYR2 | Likely pathogenic | criteria provided, single submitter |
| 208397 | NM_001035.3(RYR2):c.2238A>C (p.Gln746His) | RYR2 | Likely pathogenic | criteria provided, single submitter |
| 208383 | NM_178860.5(SEZ6):c.678_686del (p.Thr227_Thr229del) | SEZ6 | Likely pathogenic | criteria provided, single submitter |
| 208390 | NM_198993.5(STAC2):c.257G>A (p.Arg86Lys) | STAC2 | Likely pathogenic | criteria provided, single submitter |
| 208398 | NM_032538.3(TTBK1):c.773G>A (p.Arg258Gln) | TTBK1 | Likely pathogenic | criteria provided, single submitter |
| 208389 | NM_005529.7(HSPG2):c.4233C>T (p.Tyr1411=) | HSPG2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 208384 | NM_144687.4(NLRP12):c.858C>G (p.Pro286=) | NLRP12 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 208404 | NM_001326411.2(PISD):c.322-3886G>A | LOC110121499 | Benign | criteria provided, single submitter |
| 208405 | NM_017514.5(PLXNA3):c.1847G>A (p.Arg616Gln) | PLXNA3 | Benign | criteria provided, single submitter |
| 208406 | NM_015316.3(PPP1R13B):c.215G>A (p.Arg72Gln) | PPP1R13B | Benign | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 16 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| RYR2 | Orphanet:293888 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant |
| RYR2 | Orphanet:293899 | Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant |
| RYR2 | Orphanet:293910 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant |
| RYR2 | Orphanet:3286 | Catecholaminergic polymorphic ventricular tachycardia |
| B4GAT1 | Orphanet:899 | Walker-Warburg syndrome |
| NLRP12 | Orphanet:247868 | NLRP12-associated hereditary periodic fever syndrome |
| FREM2 | Orphanet:2052 | Fraser syndrome |
| FREM2 | Orphanet:93100 | Renal agenesis, unilateral |
| FREM2 | Orphanet:98949 | Complete cryptophthalmia |
| GTF2IRD1 | Orphanet:904 | Williams syndrome |
| HSPG2 | Orphanet:1606 | 1p36 deletion syndrome |
| HSPG2 | Orphanet:1865 | Dyssegmental dysplasia, Silverman-Handmaker type |
| HSPG2 | Orphanet:800 | Schwartz-Jampel syndrome |
| ITGA6 | Orphanet:79403 | Junctional epidermolysis bullosa with pyloric atresia |
| RELA | Orphanet:530792 | RELA fusion-positive ependymoma |
| RELA | Orphanet:596759 | Combined immunodeficiency due to RELA haploinsufficiency |
Cohort genes → proteins
20 cohort genes, 20 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 20 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| RYR2 | HGNC:10484 | ENSG00000198626 | Q92736 | Ryanodine receptor 2 | clinvar |
| PPP1R13B | HGNC:14950 | ENSG00000088808 | Q96KQ4 | Apoptosis-stimulating of p53 protein 1 | clinvar |
| B4GAT1 | HGNC:15685 | ENSG00000174684 | O43505 | Beta-1,4-glucuronyltransferase 1 | clinvar |
| SEZ6 | HGNC:15955 | ENSG00000063015 | Q53EL9 | Seizure protein 6 homolog | clinvar |
| PDZRN3 | HGNC:17704 | ENSG00000121440 | Q9UPQ7 | E3 ubiquitin-protein ligase PDZRN3 | clinvar |
| TTBK1 | HGNC:19140 | ENSG00000146216 | Q5TCY1 | Tau-tubulin kinase 1 | clinvar |
| NLRP12 | HGNC:22938 | ENSG00000142405 | P59046 | NACHT, LRR and PYD domains-containing protein 12 | clinvar |
| GPR153 | HGNC:23618 | ENSG00000158292 | Q6NV75 | Probable G-protein coupled receptor 153 | clinvar |
| STAC2 | HGNC:23990 | ENSG00000141750 | Q6ZMT1 | SH3 and cysteine-rich domain-containing protein 2 | clinvar |
| B3GNT6 | HGNC:24141 | ENSG00000198488 | Q6ZMB0 | Acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase | clinvar |
| FREM2 | HGNC:25396 | ENSG00000150893 | Q5SZK8 | FRAS1-related extracellular matrix protein 2 | clinvar |
| ARL16 | HGNC:27902 | ENSG00000214087 | Q0P5N6 | ADP-ribosylation factor-like protein 16 | clinvar |
| GALNT4 | HGNC:4126 | ENSG00000257594 | Q8N4A0 | Polypeptide N-acetylgalactosaminyltransferase 4 | clinvar |
| GTF2IRD1 | HGNC:4661 | ENSG00000006704 | Q9UHL9 | General transcription factor II-I repeat domain-containing protein 1 | clinvar |
| HSPG2 | HGNC:5273 | ENSG00000142798 | P98160 | Basement membrane-specific heparan sulfate proteoglycan core protein | clinvar |
| ITGA6 | HGNC:6142 | ENSG00000091409 | P23229 | Integrin alpha-6 | clinvar |
| MEST | HGNC:7028 | ENSG00000106484 | Q5EB52 | Mesoderm-specific transcript homolog protein | clinvar |
| PLXNA3 | HGNC:9101 | ENSG00000130827 | P51805 | Plexin-A3 | clinvar |
| PTGIS | HGNC:9603 | ENSG00000124212 | Q16647 | Prostacyclin synthase | clinvar |
| RELA | HGNC:9955 | ENSG00000173039 | Q04206 | Transcription factor p65 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| RYR2 | Ryanodine receptor 2 | Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering cardiac muscle contraction. |
| PPP1R13B | Apoptosis-stimulating of p53 protein 1 | Regulator that plays a central role in regulation of apoptosis via its interaction with p53/TP53. |
| B4GAT1 | Beta-1,4-glucuronyltransferase 1 | Beta-1,4-glucuronyltransferase involved in O-mannosylation of alpha-dystroglycan (DAG1). |
| SEZ6 | Seizure protein 6 homolog | May play a role in cell-cell recognition and in neuronal membrane signaling. |
| PDZRN3 | E3 ubiquitin-protein ligase PDZRN3 | E3 ubiquitin-protein ligase. |
| TTBK1 | Tau-tubulin kinase 1 | Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. |
| NLRP12 | NACHT, LRR and PYD domains-containing protein 12 | Plays an essential role as an potent mitigator of inflammation. |
| GPR153 | Probable G-protein coupled receptor 153 | Orphan receptor. |
| STAC2 | SH3 and cysteine-rich domain-containing protein 2 | Plays a redundant role in promoting the expression of calcium channel CACNA1S at the cell membrane, and thereby contributes to increased channel activity. |
| B3GNT6 | Acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase | Beta-1,3-N-acetylglucosaminyltransferase that synthesizes the core 3 structure of the O-glycan, an important precursor in the biosynthesis of mucin-type glycoproteins. |
| FREM2 | FRAS1-related extracellular matrix protein 2 | Extracellular matrix protein required for maintenance of the integrity of the skin epithelium and for maintenance of renal epithelia. |
| ARL16 | ADP-ribosylation factor-like protein 16 | Required for the trafficking of ciliary proteins IFT140 and INPP5E from the Golgi to the cilia, thus playing a role in ciliogenesis. |
| GALNT4 | Polypeptide N-acetylgalactosaminyltransferase 4 | Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. |
| GTF2IRD1 | General transcription factor II-I repeat domain-containing protein 1 | May be a transcription regulator involved in cell-cycle progression and skeletal muscle differentiation. |
| HSPG2 | Basement membrane-specific heparan sulfate proteoglycan core protein | Integral component of basement membranes. |
| ITGA6 | Integrin alpha-6 | Integrin alpha-6/beta-1 (ITGA6:ITGB1) is a receptor for laminin on platelets. |
| MEST | Mesoderm-specific transcript homolog protein | Plays an important role in enabling neurons to transition from bipolar to multipolar shapes, a process essential for their correct migration toward the cortical plate during brain development. |
| PLXNA3 | Plexin-A3 | Coreceptor for SEMA3A and SEMA3F. |
| PTGIS | Prostacyclin synthase | Catalyzes the biosynthesis and metabolism of eicosanoids. |
| RELA | Transcription factor p65 | NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as infl… |
Protein-family classification
Druggable: 11 · Difficult: 5 · Unknown: 4 · Druggable fraction: 0.55
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.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Complement | 1 | 13.4× | 0.239 |
| Antibody/Immunoglobulin | 3 | 4.4× | 0.239 |
| Enzyme (other) | 4 | 2.4× | 0.239 |
| Ion channel | 1 | 5.6× | 0.371 |
| Scaffold/PPI | 2 | 1.7× | 0.582 |
| Kinase | 1 | 1.4× | 0.646 |
| Transcription factor | 3 | 1.2× | 0.646 |
| GPCR | 1 | 1.2× | 0.646 |
| Other/Unknown | 4 | 0.4× | 1.000 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| RYR2 | Ion channel | yes | RIH_dom, B30.2/SPRY, EF_hand_dom | |
| PPP1R13B | Scaffold/PPI | no | SH3_domain, Ankyrin_rpt, ASPP1_RA | |
| B4GAT1 | Enzyme (other) | yes | 2.4.1.149 | B4GAT1 |
| SEZ6 | Complement | yes | Sushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf | |
| PDZRN3 | Transcription factor | no | Znf_TRAF, PDZ, Znf_RING | |
| TTBK1 | Kinase | yes | 2.7.11.26 | Prot_kinase_dom, Kinase-like_dom_sf, Protein_kinase_ATP_BS |
| NLRP12 | Other/Unknown | no | Leu-rich_rpt, DAPIN, NACHT_NTPase | |
| GPR153 | GPCR | yes | GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, GPR153 | |
| STAC2 | Scaffold/PPI | no | SH3_domain, PKC_DAG/PE, Stac2_SH3 | |
| B3GNT6 | Enzyme (other) | yes | 2.4.1.147 | Glyco_trans_31 |
| FREM2 | Other/Unknown | no | Calx_beta, CalX-like_sf, CSPG_rpt | |
| ARL16 | Other/Unknown | no | Small_GTPase_ARF/SAR, P-loop_NTPase | |
| GALNT4 | Enzyme (other) | yes | 2.4.1.41 | Ricin_B_lectin, Glyco_trans_2-like, Nucleotide-diphossugar_trans |
| GTF2IRD1 | Transcription factor | no | GTF2I, TF_II-I, GTF2I-like_rpt_sf | |
| HSPG2 | Antibody/Immunoglobulin | yes | Laminin_IV, SEA_dom, EGF | |
| ITGA6 | Antibody/Immunoglobulin | yes | Integrin_alpha, FG-GAP, Int_alpha_beta-p | |
| MEST | Other/Unknown | no | AB_hydrolase_1, Epox_hydrolase-like, AB_hydrolase_fold | |
| PLXNA3 | Antibody/Immunoglobulin | yes | Semap_dom, Plexin_repeat, IPT_dom | |
| PTGIS | Enzyme (other) | yes | 5.3.99.4 | Cyt_P450, Cyt_P450_E_grp-IV, Cyt_P450_CYP7A1-type |
| RELA | Transcription factor | no | NFkB/Dor, IPT_dom, p53-like_TF_DNA-bd_sf |
Expression context
Cohort genes with no expression data: 0.
16 cohort genes are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 20 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| popliteal artery | 3 |
| tibial artery | 3 |
| right hemisphere of cerebellum | 2 |
| blood vessel layer | 2 |
| mucosa of stomach | 2 |
| lateral nuclear group of thalamus | 2 |
| prefrontal cortex | 2 |
| rectum | 2 |
| heart right ventricle | 1 |
| left ventricle myocardium | 1 |
| myocardium | 1 |
| left lobe of thyroid gland | 1 |
| right lobe of thyroid gland | 1 |
| thyroid gland | 1 |
| endothelial cell | 1 |
| middle temporal gyrus | 1 |
| pons | 1 |
| cortical plate | 1 |
| ganglionic eminence | 1 |
| hair follicle | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| RYR2 | 210 | broad | marker | heart right ventricle, left ventricle myocardium, myocardium |
| PPP1R13B | 277 | ubiquitous | marker | right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland |
| B4GAT1 | 285 | ubiquitous | marker | endothelial cell, middle temporal gyrus, pons |
| SEZ6 | 167 | broad | marker | cortical plate, ganglionic eminence, right hemisphere of cerebellum |
| PDZRN3 | 282 | broad | marker | blood vessel layer, hair follicle, mucosa of stomach |
| TTBK1 | 126 | broad | yes | lateral nuclear group of thalamus, prefrontal cortex, postcentral gyrus |
| NLRP12 | 117 | tissue_specific | marker | blood, monocyte, leukocyte |
| GPR153 | 265 | ubiquitous | yes | ileal mucosa, lateral nuclear group of thalamus, triceps brachii |
| STAC2 | 164 | broad | marker | popliteal artery, tibial artery, right frontal lobe |
| B3GNT6 | 76 | tissue_specific | yes | rectum, mucosa of sigmoid colon, mucosa of transverse colon |
| FREM2 | 160 | broad | marker | adrenal tissue, kidney epithelium, renal medulla |
| ARL16 | 134 | ubiquitous | marker | metanephros cortex, prefrontal cortex, right uterine tube |
| GALNT4 | 132 | ubiquitous | yes | endometrium, rectum, duodenum |
| GTF2IRD1 | 270 | ubiquitous | marker | lower esophagus mucosa, hindlimb stylopod muscle, tibialis anterior |
| HSPG2 | 271 | ubiquitous | marker | saphenous vein, popliteal artery, tibial artery |
| ITGA6 | 297 | ubiquitous | marker | tibial nerve, sural nerve, dorsal root ganglion |
| MEST | 287 | ubiquitous | marker | cartilage tissue, placenta, secondary oocyte |
| PLXNA3 | 204 | ubiquitous | marker | adenohypophysis, stromal cell of endometrium, right hemisphere of cerebellum |
| PTGIS | 232 | broad | marker | parietal pleura, right coronary artery, blood vessel layer |
| RELA | 295 | ubiquitous | marker | mucosa of stomach, popliteal artery, tibial artery |
Protein interactions among cohort
Intra-cohort edges: 1.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| RELA | 8,449 |
| ITGA6 | 3,130 |
| RYR2 | 2,653 |
| HSPG2 | 2,463 |
| GPR153 | 2,092 |
| PTGIS | 2,053 |
| SEZ6 | 2,025 |
| MEST | 1,862 |
| STAC2 | 1,811 |
| TTBK1 | 1,784 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| PPP1R13B | RELA | string_interaction |
Structural data
PDB: 12 · AlphaFold-only: 8 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| RELA | Q04206 | 88 |
| RYR2 | Q92736 | 26 |
| TTBK1 | Q5TCY1 | 16 |
| GTF2IRD1 | Q9UHL9 | 4 |
| NLRP12 | P59046 | 3 |
| STAC2 | Q6ZMT1 | 3 |
| PDZRN3 | Q9UPQ7 | 2 |
| GALNT4 | Q8N4A0 | 2 |
| HSPG2 | P98160 | 2 |
| ITGA6 | P23229 | 2 |
| PTGIS | Q16647 | 2 |
| PPP1R13B | Q96KQ4 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| MEST | Q5EB52 | 91.88 |
| B4GAT1 | O43505 | 88.46 |
| B3GNT6 | Q6ZMB0 | 87.19 |
| ARL16 | Q0P5N6 | 86.91 |
| PLXNA3 | P51805 | 84.77 |
| SEZ6 | Q53EL9 | 70.43 |
| GPR153 | Q6NV75 | 65.60 |
| FREM2 | Q5SZK8 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 172. Enrichment computed across 20 evidence-associated genes (11 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 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Laminin interactions | 2 | 69.2× | 0.062 | HSPG2, ITGA6 |
| Defective LARGE causes MDDGA6 and MDDGB6 | 1 | 346.1× | 0.070 | B4GAT1 |
| p75NTR signals via NF-kB | 1 | 173.0× | 0.070 | RELA |
| CLEC7A/inflammasome pathway | 1 | 173.0× | 0.070 | RELA |
| DEx/H-box helicases activate type I IFN and inflammatory cytokines production | 1 | 148.3× | 0.070 | RELA |
| IkBA variant leads to EDA-ID | 1 | 148.3× | 0.070 | RELA |
| Regulation of NFE2L2 gene expression | 1 | 129.8× | 0.070 | RELA |
| Interleukin-1 processing | 1 | 115.3× | 0.070 | RELA |
| Activation of PUMA and translocation to mitochondria | 1 | 103.8× | 0.070 | PPP1R13B |
| Inflammasomes | 1 | 103.8× | 0.070 | RELA |
| Cell recruitment (pro-inflammatory response) | 1 | 103.8× | 0.070 | RELA |
| ZBP1(DAI) mediated induction of type I IFNs | 1 | 94.4× | 0.070 | RELA |
| Regulated proteolysis of p75NTR | 1 | 94.4× | 0.070 | RELA |
| Type I hemidesmosome assembly | 1 | 94.4× | 0.070 | ITGA6 |
| Eicosanoids | 1 | 86.5× | 0.070 | PTGIS |
| SUMOylation of immune response proteins | 1 | 86.5× | 0.070 | RELA |
| TP53 Regulates Transcription of Death Receptors and Ligands | 1 | 86.5× | 0.070 | PPP1R13B |
| NF-kB is activated and signals survival | 1 | 79.9× | 0.070 | RELA |
| Diseases of Immune System | 1 | 79.9× | 0.070 | RELA |
| Diseases associated with the TLR signaling cascade | 1 | 79.9× | 0.070 | RELA |
| Downstream signaling events of B Cell Receptor (BCR) | 1 | 74.2× | 0.070 | RELA |
| Defective EXT2 causes exostoses 2 | 1 | 74.2× | 0.070 | HSPG2 |
| Defective EXT1 causes exostoses 1, TRPS2 and CHDS | 1 | 74.2× | 0.070 | HSPG2 |
| Regulation of TP53 Activity through Association with Co-factors | 1 | 74.2× | 0.070 | PPP1R13B |
| Matriglycan biosynthesis on DAG1 | 1 | 74.2× | 0.070 | B4GAT1 |
| Synthesis of Prostaglandins (PG) and Thromboxanes (TX) | 1 | 69.2× | 0.070 | PTGIS |
| SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion | 1 | 69.2× | 0.070 | PLXNA3 |
| TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain | 1 | 69.2× | 0.070 | PPP1R13B |
| Developmental Lineage of Mammary Stem Cells | 1 | 69.2× | 0.070 | ITGA6 |
| RIP-mediated NFkB activation via ZBP1 | 1 | 61.1× | 0.070 | RELA |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 18 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| transition between slow and fast fiber | 1 | 936.2× | 0.026 | GTF2IRD1 |
| regulation of interleukin-18 production | 1 | 936.2× | 0.026 | NLRP12 |
| positive regulation of astrocyte activation | 1 | 936.2× | 0.026 | TTBK1 |
| establishment of protein localization to endoplasmic reticulum | 1 | 936.2× | 0.026 | RYR2 |
| cellular response to interleukin-6 | 2 | 110.1× | 0.026 | PTGIS, RELA |
| response to muscle stretch | 2 | 85.1× | 0.026 | RYR2, RELA |
| negative regulation of non-canonical NF-kappaB signal transduction | 2 | 56.7× | 0.026 | NLRP12, RELA |
| protein O-linked glycosylation via N-acetylgalactosamine | 2 | 48.0× | 0.026 | B3GNT6, GALNT4 |
| negative regulation of extrinsic apoptotic signaling pathway | 2 | 46.8× | 0.026 | ITGA6, RELA |
| embryo implantation | 2 | 39.0× | 0.026 | HSPG2, PTGIS |
| olfactory nerve formation | 1 | 468.1× | 0.030 | PLXNA3 |
| prolactin signaling pathway | 1 | 468.1× | 0.030 | RELA |
| negative regulation of Toll signaling pathway | 1 | 468.1× | 0.030 | NLRP12 |
| Purkinje myocyte to ventricular cardiac muscle cell signaling | 1 | 468.1× | 0.030 | RYR2 |
| cellular response to interleukin-1 | 2 | 31.2× | 0.030 | PTGIS, RELA |
| positive regulation of interleukin-1 beta production | 2 | 28.8× | 0.030 | NLRP12, RELA |
| negative regulation of synaptic transmission, cholinergic | 1 | 312.1× | 0.031 | HSPG2 |
| type B pancreatic cell apoptotic process | 1 | 312.1× | 0.031 | RYR2 |
| regulation of AV node cell action potential | 1 | 312.1× | 0.031 | RYR2 |
| regulation of atrial cardiac muscle cell action potential | 1 | 312.1× | 0.031 | RYR2 |
| positive regulation of voltage-gated calcium channel activity | 1 | 312.1× | 0.031 | STAC2 |
| positive regulation of miRNA metabolic process | 1 | 312.1× | 0.031 | RELA |
| protein O-linked glycosylation | 2 | 25.0× | 0.031 | B3GNT6, GALNT4 |
| left ventricular cardiac muscle tissue morphogenesis | 1 | 234.1× | 0.032 | RYR2 |
| negative regulation of glycoprotein biosynthetic process | 1 | 234.1× | 0.032 | MEST |
| ectodermal cell differentiation | 1 | 234.1× | 0.032 | ITGA6 |
| toll-like receptor TLR6:TLR2 signaling pathway | 1 | 234.1× | 0.032 | RELA |
| obsolete positive regulation of sequestering of calcium ion | 1 | 234.1× | 0.032 | RYR2 |
| neuron projection guidance | 1 | 234.1× | 0.032 | PLXNA3 |
| radial glia-guided pyramidal neuron migration | 1 | 234.1× | 0.032 | MEST |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 3 · Undrugged: 17
Druggability breadth: 9 of 20 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.
| Symbol | Example approved molecule |
|---|---|
| RELA | INDOPROFEN |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| RELA | 17 | 4 |
| RYR2 | 1 | 2 |
| PTGIS | 1 | 2 |
| PPP1R13B | 0 | 0 |
| B4GAT1 | 0 | 0 |
| SEZ6 | 0 | 0 |
| PDZRN3 | 0 | 0 |
| TTBK1 | 0 | 0 |
| NLRP12 | 0 | 0 |
| GPR153 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| INDOPROFEN | 4 | RELA |
| VAMOROLONE | 4 | RELA |
| BORTEZOMIB | 4 | RELA |
| DEXAMETHASONE | 4 | RELA |
| SULFASALAZINE | 4 | RELA |
| GEFITINIB | 4 | RELA |
| CURCUMIN | 3 | RELA |
| RESVERATROL | 3 | RELA |
| IXAZOMIB | 3 | RELA |
| WITHANOLIDE D | 3 | RELA |
| TRIPTOLIDE | 3 | RELA |
| ALADORIAN | 2 | RYR2 |
| PIRMAGREL | 2 | PTGIS |
| FRENTIZOLE | 2 | RELA |
| LAPACHONE | 2 | RELA |
| SANGUINARIUM | 2 | RELA |
| URSOLIC ACID | 2 | RELA |
| AS-602868 | 1 | RELA |
| WITHAFERIN A | 1 | RELA |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 5.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| RELA | 422 | Binding:417, Functional:4, ADMET:1 |
| TTBK1 | 74 | Binding:74 |
| MEST | 20 | Binding:20 |
| RYR2 | 15 | Binding:15 |
| PTGIS | 12 | Binding:12 |
| ITGA6 | 3 | Binding:3 |
| GPR153 | 2 | Binding:2 |
| HSPG2 | 2 | Binding:2 |
| B3GNT6 | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| B4GAT1 | 2.4.1.149 | N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase |
| TTBK1 | 2.7.11.26 | tau-protein kinase |
| B3GNT6 | 2.4.1.147 | acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase |
| GALNT4 | 2.4.1.41 | polypeptide N-acetylgalactosaminyltransferase |
| PTGIS | 5.3.99.4 | prostaglandin-I synthase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| RELA | 422 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 20; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
19 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.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| INDOPROFEN | 4 | RELA |
| VAMOROLONE | 4 | RELA |
| BORTEZOMIB | 4 | RELA |
| DEXAMETHASONE | 4 | RELA |
| SULFASALAZINE | 4 | RELA |
| GEFITINIB | 4 | RELA |
| CURCUMIN | 3 | RELA |
| RESVERATROL | 3 | RELA |
| IXAZOMIB | 3 | RELA |
| WITHANOLIDE D | 3 | RELA |
| TRIPTOLIDE | 3 | RELA |
| ALADORIAN | 2 | RYR2 |
| PIRMAGREL | 2 | PTGIS |
| FRENTIZOLE | 2 | RELA |
| LAPACHONE | 2 | RELA |
| SANGUINARIUM | 2 | RELA |
| URSOLIC ACID | 2 | RELA |
| AS-602868 | 1 | RELA |
| WITHAFERIN A | 1 | RELA |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | RELA |
| B | Phased (≥1) drug, not yet approved | 2 | RYR2, PTGIS |
| C | Druggable family + PDB, no drug | 4 | TTBK1, GALNT4, HSPG2, ITGA6 |
| D | Druggable family + AlphaFold only, no drug | 5 | B4GAT1, SEZ6, GPR153, B3GNT6, PLXNA3 |
| E | Difficult family or no structure, no drug | 8 | PPP1R13B, PDZRN3, NLRP12, STAC2, FREM2, ARL16, GTF2IRD1, MEST |
Undrugged target profiles
17 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| PPP1R13B | 0 | RELA |
| B4GAT1 | 0 | — |
| SEZ6 | 0 | — |
| PDZRN3 | 0 | — |
| TTBK1 | 74 | — |
| NLRP12 | 0 | — |
| GPR153 | 2 | — |
| STAC2 | 0 | — |
| B3GNT6 | 1 | — |
| FREM2 | 0 | — |
| ARL16 | 0 | — |
| GALNT4 | 0 | — |
| GTF2IRD1 | 0 | — |
| HSPG2 | 2 | — |
| ITGA6 | 3 | — |
| MEST | 20 | — |
| PLXNA3 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.