Developmental and epileptic encephalopathy, 30
diseaseOn this page
Also known as DEE30developmental and epileptic encephalopathy 30early infantile epileptic encephalopathy caused by mutation in SIK1EIEE30epileptic encephalopathy, early infantile, 30epileptic encephalopathy, early infantile, type 30SIK1 early infantile epileptic encephalopathy
Summary
Developmental and epileptic encephalopathy, 30 (MONDO:0014595) is a disease caused by SIK1 (GenCC Definitive), with 7 cohort genes.
At a glance
- Causal gene: SIK1 (GenCC Definitive)
- Cohort genes: 7
- ClinVar variants: 1,034
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | developmental and epileptic encephalopathy, 30 |
| Mondo ID | MONDO:0014595 |
| OMIM | 616341 |
| DOID | DOID:0080465 |
| UMLS | C4225360 |
| MedGen | 898954 |
| GARD | 0016093 |
| Is cancer (heuristic) | no |
Also known as: DEE30 · developmental and epileptic encephalopathy 30 · early infantile epileptic encephalopathy caused by mutation in SIK1 · EIEE30 · epileptic encephalopathy, early infantile, 30 · epileptic encephalopathy, early infantile, type 30 · SIK1 early infantile epileptic encephalopathy
Data availability: 1,034 ClinVar variants · 2 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › syndromic disease › infantile spasms › developmental and epileptic encephalopathy, 30
Related subtypes (7): developmental and epileptic encephalopathy, 2, developmental and epileptic encephalopathy, 1, developmental and epileptic encephalopathy, 5, developmental and epileptic encephalopathy, 12, developmental and epileptic encephalopathy, 15, developmental and epileptic encephalopathy, 27, developmental and epileptic encephalopathy, 40
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
600 retrieved; paginated sample, class counts are floors:
281 likely benign, 269 uncertain significance, 22 benign, 21 conflicting classifications of pathogenicity, 4 pathogenic, 1 benign/likely benign, 1 likely pathogenic, 1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 206981 | NM_001040142.2(SCN2A):c.2995G>A (p.Glu999Lys) | SCN2A | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 190105 | NM_173354.5(SIK1):c.859C>A (p.Pro287Thr) | SIK1 | Pathogenic | no assertion criteria provided |
| 190106 | NM_173354.5(SIK1):c.1039G>T (p.Glu347Ter) | SIK1 | Pathogenic | no assertion criteria provided |
| 190107 | NM_173354.5(SIK1):c.1840C>T (p.Gln614Ter) | SIK1 | Pathogenic | no assertion criteria provided |
| 190109 | NM_173354.5(SIK1):c.1906G>A (p.Gly636Ser) | SIK1 | Pathogenic | no assertion criteria provided |
| 1703110 | NM_173354.5(SIK1):c.1839C>A (p.Cys613Ter) | SIK1 | Likely pathogenic | criteria provided, single submitter |
| 2422361 | NC_000021.8:g.(?43160998)(47754702_?)del | ABCG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1025710 | NM_173354.5(SIK1):c.1691T>C (p.Leu564Pro) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1030319 | NM_173354.5(SIK1):c.468G>A (p.Leu156=) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1036622 | NM_173354.5(SIK1):c.1783C>T (p.Arg595Trp) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1041574 | NM_173354.5(SIK1):c.938A>G (p.Gln313Arg) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1044080 | NM_173354.5(SIK1):c.1634C>T (p.Ser545Leu) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1063659 | NM_173354.5(SIK1):c.2201T>C (p.Ile734Thr) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1137642 | NM_173354.5(SIK1):c.1463-5C>A | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1362958 | NM_173354.5(SIK1):c.835C>G (p.Arg279Gly) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1372665 | NM_173354.5(SIK1):c.1784G>A (p.Arg595Gln) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1393532 | NM_173354.5(SIK1):c.1235C>T (p.Ser412Leu) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1408200 | NM_173354.5(SIK1):c.1642G>A (p.Ala548Thr) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1462942 | NM_173354.5(SIK1):c.1279G>A (p.Gly427Arg) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1475064 | NM_173354.5(SIK1):c.691A>G (p.Thr231Ala) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1627773 | NM_173354.5(SIK1):c.1055A>G (p.Gln352Arg) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1763111 | NM_173354.5(SIK1):c.836G>A (p.Arg279Gln) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 190108 | NM_173354.5(SIK1):c.1897C>T (p.Gln633Ter) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1912697 | NM_173354.5(SIK1):c.1793G>C (p.Gly598Ala) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2181702 | NM_173354.5(SIK1):c.692C>T (p.Thr231Met) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2199574 | NM_173354.5(SIK1):c.2152G>A (p.Ala718Thr) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2898107 | NM_173354.5(SIK1):c.1066C>T (p.Pro356Ser) | SIK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1409580 | NC_000021.8:g.(?43160998)(47865240_?)dup | KRTAP12-2 | Uncertain significance | criteria provided, single submitter |
| 1055976 | NC_000021.8:g.(?44838130)(45196150_?)dup | RRP1B | Uncertain significance | criteria provided, single submitter |
| 1000093 | NM_173354.5(SIK1):c.1988T>C (p.Leu663Ser) | SIK1 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 7 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| SIK1 | Definitive | Autosomal dominant | developmental and epileptic encephalopathy, 30 | 7 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| SIK1 | Orphanet:1934 | Early infantile developmental and epileptic encephalopathy |
| SIK1 | Orphanet:697160 | Infantile epileptic spasms syndrome |
| SCN2A | Orphanet:140927 | Self-limited neonatal-infantile epilepsy |
| SCN2A | Orphanet:1934 | Early infantile developmental and epileptic encephalopathy |
| SCN2A | Orphanet:2131 | Alternating hemiplegia of childhood |
| SCN2A | Orphanet:293181 | Epilepsy of infancy with migrating focal seizures |
| SCN2A | Orphanet:306 | Self-limited infantile epilepsy |
| SCN2A | Orphanet:33069 | Dravet syndrome |
| SCN2A | Orphanet:36387 | Genetic epilepsy with febrile seizure plus |
| SCN2A | Orphanet:697160 | Infantile epileptic spasms syndrome |
Cohort genes → proteins
7 cohort genes, 7 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 7 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| SIK1 | HGNC:11142 | ENSG00000142178 | P57059 | Serine/threonine-protein kinase SIK1 | gencc,clinvar |
| SCN2A | HGNC:10588 | ENSG00000136531 | Q99250 | Sodium channel protein type 2 subunit alpha | clinvar |
| KRTAP12-2 | HGNC:20530 | ENSG00000221864 | P59991 | Keratin-associated protein 12-2 | clinvar |
| RRP1B | HGNC:23818 | ENSG00000160208 | Q14684 | Ribosomal RNA processing protein 1 homolog B | clinvar |
| AGPAT3 | HGNC:326 | ENSG00000160216 | Q9NRZ7 | 1-acyl-sn-glycerol-3-phosphate acyltransferase gamma | clinvar |
| ABCG1 | HGNC:73 | ENSG00000160179 | P45844 | ATP-binding cassette sub-family G member 1 | clinvar |
| PDXK | HGNC:8819 | ENSG00000160209 | O00764 | Pyridoxal kinase | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| SIK1 | Serine/threonine-protein kinase SIK1 | Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression. |
| SCN2A | Sodium channel protein type 2 subunit alpha | Mediates the voltage-dependent sodium ion permeability of excitable membranes. |
| KRTAP12-2 | Keratin-associated protein 12-2 | In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through t… |
| RRP1B | Ribosomal RNA processing protein 1 homolog B | Positively regulates DNA damage-induced apoptosis by acting as a transcriptional coactivator of proapoptotic target genes of the transcriptional activator E2F1. |
| AGPAT3 | 1-acyl-sn-glycerol-3-phosphate acyltransferase gamma | Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone. |
| ABCG1 | ATP-binding cassette sub-family G member 1 | Catalyzes the efflux of phospholipids such as sphingomyelin, cholesterol and its oxygenated derivatives like 7beta-hydroxycholesterol and this transport is coupled to hydrolysis of ATP. |
| PDXK | Pyridoxal kinase | Catalyzes the phosphorylation of the dietary vitamin B6 vitamers pyridoxal (PL), pyridoxine (PN) and pyridoxamine (PM) to form pyridoxal 5’-phosphate (PLP), pyridoxine 5’-phosphate (PNP) and pyridoxamine 5’-phosphate (PMP), respectively. |
Protein-family classification
Druggable: 5 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.71
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 |
|---|---|---|---|
| Kinase | 2 | 7.9× | 0.121 |
| Ion channel | 1 | 15.9× | 0.144 |
| Transporter | 1 | 11.1× | 0.144 |
| Enzyme (other) | 1 | 1.7× | 0.571 |
| Other/Unknown | 2 | 0.5× | 0.968 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| SIK1 | Kinase | yes | Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf | |
| SCN2A | Ion channel | yes | IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom | |
| KRTAP12-2 | Other/Unknown | no | KRTAP_PMG | |
| RRP1B | Other/Unknown | no | RRP1 | |
| AGPAT3 | Enzyme (other) | yes | 2.3.1.51 | Plipid/glycerol_acylTrfase, Acyltransf_C |
| ABCG1 | Transporter | yes | ABC_transporter-like_ATP-bd, AAA+_ATPase, Pigment_permease/Abcg | |
| PDXK | Kinase | yes | 2.7.1.35 | PyrdxlKinase, PM/HMP-P_kinase-1, Ribokinase-like |
Expression context
Cohort genes with no expression data: 0.
6 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) | 1 |
| broad (>20) | 6 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| Brodmann (1909) area 23 | 2 |
| middle temporal gyrus | 2 |
| mucosa of stomach | 1 |
| skin of abdomen | 1 |
| zone of skin | 1 |
| cerebellar vermis | 1 |
| colonic epithelium | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| sural nerve | 1 |
| germinal epithelium of ovary | 1 |
| gingiva | 1 |
| gingival epithelium | 1 |
| lateral globus pallidus | 1 |
| left adrenal gland | 1 |
| right adrenal gland | 1 |
| right adrenal gland cortex | 1 |
| adult organism | 1 |
| left testis | 1 |
| right testis | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| SIK1 | 138 | not_expressed | marker | mucosa of stomach, skin of abdomen, zone of skin |
| SCN2A | 187 | broad | marker | middle temporal gyrus, Brodmann (1909) area 23, cerebellar vermis |
| KRTAP12-2 | 16 | yes | male germ line stem cell (sensu Vertebrata) in testis, sural nerve, colonic epithelium | |
| RRP1B | 286 | ubiquitous | marker | germinal epithelium of ovary, gingival epithelium, gingiva |
| AGPAT3 | 274 | ubiquitous | marker | lateral globus pallidus, middle temporal gyrus, Brodmann (1909) area 23 |
| ABCG1 | 270 | ubiquitous | marker | right adrenal gland, left adrenal gland, right adrenal gland cortex |
| PDXK | 295 | ubiquitous | marker | left testis, right testis, adult organism |
Protein interactions among cohort
Intra-cohort edges: 1.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| RRP1B | 3,651 |
| SCN2A | 2,810 |
| ABCG1 | 2,178 |
| AGPAT3 | 2,081 |
| PDXK | 1,899 |
| SIK1 | 1,840 |
| KRTAP12-2 | 773 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| PDXK | RRP1B | string_interaction |
Structural data
PDB: 4 · AlphaFold-only: 3 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| PDXK | O00764 | 10 |
| SCN2A | Q99250 | 5 |
| ABCG1 | P45844 | 5 |
| RRP1B | Q14684 | 2 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| AGPAT3 | Q9NRZ7 | 94.63 |
| KRTAP12-2 | P59991 | 70.96 |
| SIK1 | P57059 | 61.31 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 28. Enrichment computed across 7 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Vitamin B6 activation to pyridoxal phosphate | 1 | 634.4× | 0.044 | PDXK |
| HDL remodeling | 1 | 190.3× | 0.046 | ABCG1 |
| ABC transporters in lipid homeostasis | 1 | 100.2× | 0.046 | ABCG1 |
| Plasma lipoprotein remodeling | 1 | 79.3× | 0.046 | ABCG1 |
| Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes | 1 | 79.3× | 0.046 | SIK1 |
| NR1H2 and NR1H3-mediated signaling | 1 | 65.6× | 0.046 | ABCG1 |
| Interaction between L1 and Ankyrins | 1 | 61.4× | 0.046 | SCN2A |
| R-HSA-400253 | 1 | 57.7× | 0.046 | SIK1 |
| Phase 0 - rapid depolarisation | 1 | 57.7× | 0.046 | SCN2A |
| Sensory perception of taste | 1 | 56.0× | 0.046 | SCN2A |
| NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux | 1 | 51.4× | 0.046 | ABCG1 |
| Synthesis of PA | 1 | 48.8× | 0.046 | AGPAT3 |
| Sensory perception of sweet, bitter, and umami (glutamate) taste | 1 | 46.4× | 0.046 | SCN2A |
| Plasma lipoprotein assembly, remodeling, and clearance | 1 | 38.1× | 0.052 | ABCG1 |
| COPI-independent Golgi-to-ER retrograde traffic | 1 | 34.6× | 0.053 | AGPAT3 |
| ABC-family protein mediated transport | 1 | 20.2× | 0.081 | ABCG1 |
| L1CAM interactions | 1 | 20.0× | 0.081 | SCN2A |
| Cardiac conduction | 1 | 18.1× | 0.082 | SCN2A |
| Signaling by Nuclear Receptors | 1 | 17.0× | 0.082 | ABCG1 |
| Sensory Perception | 1 | 15.9× | 0.082 | SCN2A |
| Developmental Biology | 2 | 4.8× | 0.082 | SCN2A, KRTAP12-2 |
| Muscle contraction | 1 | 12.9× | 0.096 | SCN2A |
| Keratinization | 1 | 9.3× | 0.125 | KRTAP12-2 |
| Axon guidance | 1 | 7.5× | 0.147 | SCN2A |
| Nervous system development | 1 | 7.2× | 0.148 | SCN2A |
| Transport of small molecules | 1 | 4.2× | 0.233 | ABCG1 |
| Neutrophil degranulation | 1 | 3.9× | 0.242 | PDXK |
| Signal Transduction | 1 | 1.7× | 0.463 | ABCG1 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| pyridoxal 5’-phosphate salvage | 1 | 2808.7× | 0.011 | PDXK |
| pyridoxal metabolic process | 1 | 2808.7× | 0.011 | PDXK |
| intrinsic apoptotic signaling pathway in response to osmotic stress | 1 | 1404.3× | 0.011 | SCN2A |
| pyridoxamine metabolic process | 1 | 1404.3× | 0.011 | PDXK |
| glycoprotein transport | 1 | 936.2× | 0.011 | ABCG1 |
| cellular response to high density lipoprotein particle stimulus | 1 | 936.2× | 0.011 | ABCG1 |
| negative regulation of triglyceride biosynthetic process | 1 | 702.2× | 0.011 | SIK1 |
| obsolete negative regulation of CREB transcription factor activity | 1 | 702.2× | 0.011 | SIK1 |
| regulation of myotube differentiation | 1 | 561.7× | 0.013 | SIK1 |
| response to lipid | 1 | 401.2× | 0.015 | ABCG1 |
| positive regulation of anoikis | 1 | 312.1× | 0.015 | SIK1 |
| negative regulation of cholesterol storage | 1 | 255.3× | 0.015 | ABCG1 |
| negative regulation of macrophage derived foam cell differentiation | 1 | 216.1× | 0.015 | ABCG1 |
| CDP-diacylglycerol biosynthetic process | 1 | 216.1× | 0.015 | AGPAT3 |
| intracellular cholesterol transport | 1 | 216.1× | 0.015 | ABCG1 |
| anoikis | 1 | 216.1× | 0.015 | SIK1 |
| amyloid precursor protein catabolic process | 1 | 200.6× | 0.015 | ABCG1 |
| phospholipid efflux | 1 | 187.2× | 0.015 | ABCG1 |
| positive regulation of cholesterol biosynthetic process | 1 | 187.2× | 0.015 | ABCG1 |
| regulation of cholesterol metabolic process | 1 | 187.2× | 0.015 | ABCG1 |
| xenobiotic detoxification by transmembrane export across the plasma membrane | 1 | 187.2× | 0.015 | ABCG1 |
| negative regulation of GTPase activity | 1 | 175.5× | 0.015 | RRP1B |
| low-density lipoprotein particle remodeling | 1 | 175.5× | 0.015 | ABCG1 |
| phospholipid homeostasis | 1 | 165.2× | 0.015 | ABCG1 |
| regulation of sodium ion transport | 1 | 156.0× | 0.015 | SIK1 |
| reverse cholesterol transport | 1 | 156.0× | 0.015 | ABCG1 |
| host-mediated activation of viral transcription | 1 | 147.8× | 0.015 | RRP1B |
| positive regulation of amyloid-beta formation | 1 | 147.8× | 0.015 | ABCG1 |
| high-density lipoprotein particle remodeling | 1 | 133.8× | 0.016 | ABCG1 |
| negative regulation of gluconeogenesis | 1 | 133.8× | 0.016 | SIK1 |
Therapeutics
Drug target analysis
Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 4
Druggability breadth: 4 of 7 evidence-associated genes (57%) 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 |
|---|---|
| SIK1 | FEDRATINIB |
| SCN2A | BEPRIDIL |
| PDXK | SUNITINIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| SCN2A | 99 | 4 |
| SIK1 | 19 | 4 |
| PDXK | 6 | 4 |
| KRTAP12-2 | 0 | 0 |
| RRP1B | 0 | 0 |
| AGPAT3 | 0 | 0 |
| ABCG1 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| FEDRATINIB | 4 | SIK1 |
| AXITINIB | 4 | SIK1 |
| NERATINIB | 4 | SIK1 |
| VANDETANIB | 4 | SIK1 |
| BOSUTINIB | 4 | SIK1 |
| PAZOPANIB | 4 | SIK1 |
| NINTEDANIB | 4 | SIK1 |
| SUNITINIB | 4 | PDXK, SIK1 |
| DASATINIB | 4 | SIK1 |
| MIDOSTAURIN | 4 | SIK1 |
| BEPRIDIL | 4 | SCN2A |
| DIBUCAINE | 4 | SCN2A |
| ARTICAINE | 4 | SCN2A |
| BUPIVACAINE | 4 | SCN2A |
| IMIPRAMINE | 4 | SCN2A |
| DROPERIDOL | 4 | SCN2A |
| DICYCLOMINE | 4 | SCN2A |
| TETRABENAZINE | 4 | SCN2A |
| PHENIRAMINE | 4 | SCN2A |
| PRILOCAINE | 4 | SCN2A |
| PROPOXYCAINE | 4 | SCN2A |
| PROPARACAINE | 4 | SCN2A |
| HEXYLCAINE | 4 | SCN2A |
| PRAMOXINE | 4 | SCN2A |
| BENOXINATE | 4 | SCN2A |
| QUINIDINE | 4 | SCN2A |
| FELODIPINE | 4 | SCN2A |
| PHENYTOIN | 4 | SCN2A |
| QUININE | 4 | SCN2A |
| NISOLDIPINE | 4 | SCN2A |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 2.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| SIK1 | 210 | Binding:205, Toxicity:4, ADMET:1 |
| SCN2A | 203 | Binding:172, Functional:20, ADMET:10, Toxicity:1 |
| PDXK | 21 | Binding:20, ADMET:1 |
| RRP1B | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| AGPAT3 | 2.3.1.51 | 1-acylglycerol-3-phosphate O-acyltransferase |
| PDXK | 2.7.1.35 | pyridoxal kinase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| SIK1 | 210 |
| SCN2A | 203 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 7; 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.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| FEDRATINIB | 4 | SIK1 |
| AXITINIB | 4 | SIK1 |
| NERATINIB | 4 | SIK1 |
| VANDETANIB | 4 | SIK1 |
| BOSUTINIB | 4 | SIK1 |
| PAZOPANIB | 4 | SIK1 |
| NINTEDANIB | 4 | SIK1 |
| SUNITINIB | 4 | PDXK, SIK1 |
| DASATINIB | 4 | SIK1 |
| MIDOSTAURIN | 4 | SIK1 |
| BEPRIDIL | 4 | SCN2A |
| DIBUCAINE | 4 | SCN2A |
| ARTICAINE | 4 | SCN2A |
| BUPIVACAINE | 4 | SCN2A |
| IMIPRAMINE | 4 | SCN2A |
| DROPERIDOL | 4 | SCN2A |
| DICYCLOMINE | 4 | SCN2A |
| TETRABENAZINE | 4 | SCN2A |
| PHENIRAMINE | 4 | SCN2A |
| PRILOCAINE | 4 | SCN2A |
| PROPOXYCAINE | 4 | SCN2A |
| PROPARACAINE | 4 | SCN2A |
| HEXYLCAINE | 4 | SCN2A |
| PRAMOXINE | 4 | SCN2A |
| BENOXINATE | 4 | SCN2A |
| QUINIDINE | 4 | SCN2A |
| FELODIPINE | 4 | SCN2A |
| PHENYTOIN | 4 | SCN2A |
| QUININE | 4 | SCN2A |
| NISOLDIPINE | 4 | SCN2A |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 3 | SIK1, SCN2A, PDXK |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | ABCG1 |
| D | Druggable family + AlphaFold only, no drug | 1 | AGPAT3 |
| E | Difficult family or no structure, no drug | 2 | KRTAP12-2, RRP1B |
Undrugged target profiles
4 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| RRP1B | 1 | PDXK |
| KRTAP12-2 | 0 | — |
| AGPAT3 | 0 | — |
| ABCG1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.