Developmental and epileptic encephalopathy, 12
diseaseOn this page
Also known as DEE12developmental and epileptic encephalopathy 12early infantile epileptic encephalopathy 12early infantile epileptic encephalopathy caused by mutation in PLCB1EIEE12epileptic encephalopathy, early infantile, 12epileptic encephalopathy, early infantile, type 12PLCB1 early infantile epileptic encephalopathy
Summary
Developmental and epileptic encephalopathy, 12 (MONDO:0013389) is a disease caused by PLCB1 (GenCC Strong), with 7 cohort genes.
At a glance
- Causal gene: PLCB1 (GenCC Strong)
- Cohort genes: 7
- ClinVar variants: 1,948
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | developmental and epileptic encephalopathy, 12 |
| Mondo ID | MONDO:0013389 |
| OMIM | 613722 |
| DOID | DOID:0080459 |
| UMLS | C3150988 |
| MedGen | 462338 |
| GARD | 0013318 |
| Is cancer (heuristic) | no |
Also known as: DEE12 · developmental and epileptic encephalopathy 12 · developmental and epileptic encephalopathy, 12 · early infantile epileptic encephalopathy 12 · early infantile epileptic encephalopathy caused by mutation in PLCB1 · EIEE12 · epileptic encephalopathy, early infantile, 12 · epileptic encephalopathy, early infantile, type 12 · PLCB1 early infantile epileptic encephalopathy
Data availability: 1,948 ClinVar variants · 4 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › epilepsy › epilepsy syndrome › neonatal epilepsy syndrome › malignant migrating partial seizures of infancy › developmental and epileptic encephalopathy, 12
Related subtypes (2): developmental and epileptic encephalopathy, 16, developmental and epileptic encephalopathy, 34
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:
256 likely benign, 240 uncertain significance, 30 benign/likely benign, 25 conflicting classifications of pathogenicity, 19 benign, 17 pathogenic, 8 likely pathogenic, 5 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1070278 | NC_000020.10:g.(?8608931)(8639361_?)del | PLCB1 | Pathogenic | criteria provided, single submitter |
| 1435065 | NM_015192.4(PLCB1):c.2666del (p.Lys889fs) | PLCB1 | Pathogenic | criteria provided, single submitter |
| 1451701 | NM_015192.4(PLCB1):c.967del (p.Ser323fs) | PLCB1 | Pathogenic | criteria provided, single submitter |
| 1456484 | NC_000020.10:g.(?8639165)(8698515_?)del | PLCB1 | Pathogenic | criteria provided, single submitter |
| 1069274 | NM_007254.4(PNKP):c.984del (p.Leu329fs) | PNKP | Pathogenic | criteria provided, single submitter |
| 1071624 | NM_007254.4(PNKP):c.318G>A (p.Trp106Ter) | PNKP | Pathogenic | criteria provided, single submitter |
| 1071794 | NM_007254.4(PNKP):c.1059C>A (p.Cys353Ter) | PNKP | Pathogenic | criteria provided, single submitter |
| 1074930 | NC_000019.9:g.(?50364485)(50370481_?)del | PNKP | Pathogenic | criteria provided, single submitter |
| 1075417 | NM_007254.4(PNKP):c.1299-2A>G | PNKP | Pathogenic | criteria provided, single submitter |
| 1323477 | NM_007254.4(PNKP):c.1386+1G>C | PNKP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1371267 | NM_007254.4(PNKP):c.1311T>A (p.Cys437Ter) | PNKP | Pathogenic | criteria provided, single submitter |
| 1382516 | NM_007254.4(PNKP):c.1066G>T (p.Glu356Ter) | PNKP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1412103 | NM_007254.4(PNKP):c.1390C>T (p.Arg464Ter) | PNKP | Pathogenic | criteria provided, single submitter |
| 1419965 | NM_007254.4(PNKP):c.808C>T (p.Gln270Ter) | PNKP | Pathogenic | criteria provided, single submitter |
| 1452109 | NM_007254.4(PNKP):c.1448+2T>A | PNKP | Pathogenic | criteria provided, single submitter |
| 1452440 | NM_007254.4(PNKP):c.1543dup (p.Tyr515fs) | PNKP | Pathogenic | criteria provided, single submitter |
| 1453217 | NM_007254.4(PNKP):c.756_760del (p.Thr253fs) | PNKP | Pathogenic | criteria provided, single submitter |
| 1453676 | NM_007254.4(PNKP):c.721G>T (p.Glu241Ter) | PNKP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1455443 | NM_007254.4(PNKP):c.1270_1283dup (p.Ala429fs) | PNKP | Pathogenic | criteria provided, single submitter |
| 1455884 | NM_007254.4(PNKP):c.1395_1396del (p.Glu465fs) | PNKP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1460226 | NM_007254.4(PNKP):c.847del (p.Asp283fs) | PNKP | Pathogenic | criteria provided, single submitter |
| 159788 | NM_007254.4(PNKP):c.1295_1298+6del | PNKP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1481396 | NM_015192.4(PLCB1):c.465-2A>C | PLCB1 | Likely pathogenic | criteria provided, single submitter |
| 1486443 | NM_015192.4(PLCB1):c.2208+1G>A | PLCB1 | Likely pathogenic | criteria provided, single submitter |
| 1507516 | NM_015192.4(PLCB1):c.1168-1G>A | PLCB1 | Likely pathogenic | criteria provided, single submitter |
| 1068053 | NM_007254.4(PNKP):c.199-2A>G | PNKP | Likely pathogenic | criteria provided, single submitter |
| 1467112 | NM_007254.4(PNKP):c.1298+1G>A | PNKP | Likely pathogenic | criteria provided, single submitter |
| 1497182 | NM_007254.4(PNKP):c.865+1G>A | PNKP | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1520587 | NM_007254.4(PNKP):c.1387-2A>G | PNKP | Likely pathogenic | criteria provided, single submitter |
| 1522783 | NM_007254.4(PNKP):c.636+1G>C | PNKP | Likely pathogenic | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 6 · Orphanet: 14 · 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 |
|---|---|---|---|---|
| PLCB1 | Strong | Autosomal recessive | developmental and epileptic encephalopathy, 12 | 6 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| PLCB1 | Orphanet:293181 | Epilepsy of infancy with migrating focal seizures |
| PLCB1 | 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 |
| PLCB4 | Orphanet:137888 | Auriculocondylar syndrome |
| PNKP | Orphanet:101101 | Charcot-Marie-Tooth disease type 2B2 |
| PNKP | Orphanet:1934 | Early infantile developmental and epileptic encephalopathy |
| PNKP | Orphanet:459033 | Ataxia-oculomotor apraxia type 4 |
Cohort genes → proteins
7 cohort genes, 6 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 7 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| PLCB1 | HGNC:15917 | ENSG00000182621 | Q9NQ66 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 | gencc,clinvar |
| SCN2A | HGNC:10588 | ENSG00000136531 | Q99250 | Sodium channel protein type 2 subunit alpha | clinvar |
| ALDH16A1 | HGNC:28114 | ENSG00000161618 | Q8IZ83 | Aldehyde dehydrogenase family 16 member A1 | clinvar |
| AKT1S1 | HGNC:28426 | ENSG00000204673 | Q96B36 | Proline-rich AKT1 substrate 1 | clinvar |
| PTOV1-AS2 | HGNC:51284 | ENSG00000269352 | PTOV1 antisense RNA 2 | clinvar | |
| PLCB4 | HGNC:9059 | ENSG00000101333 | Q15147 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 | clinvar |
| PNKP | HGNC:9154 | ENSG00000039650 | Q96T60 | Bifunctional polynucleotide phosphatase/kinase | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| PLCB1 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 | Catalyzes the hydrolysis of 1-phosphatidylinositol 4,5-bisphosphate into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) and mediates intracellular signaling downstream of G protein-coupled receptors. |
| SCN2A | Sodium channel protein type 2 subunit alpha | Mediates the voltage-dependent sodium ion permeability of excitable membranes. |
| AKT1S1 | Proline-rich AKT1 substrate 1 | Negative regulator of the mechanistic target of rapamycin complex 1 (mTORC1), an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and… |
| PLCB4 | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 | Activated phosphatidylinositol-specific phospholipase C enzymes catalyze the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) involved in G-protein coupled receptor signaling pathways. |
| PNKP | Bifunctional polynucleotide phosphatase/kinase | Plays a key role in the repair of DNA damage, functioning as part of both the non-homologous end-joining (NHEJ) and base excision repair (BER) pathways. |
Protein-family classification
Druggable: 4 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.57
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 |
|---|---|---|---|
| Ion channel | 1 | 15.9× | 0.147 |
| Phosphatase | 1 | 12.0× | 0.147 |
| Enzyme (other) | 2 | 3.4× | 0.147 |
| Other/Unknown | 3 | 0.8× | 0.858 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| PLCB1 | Enzyme (other) | yes | 3.1.4.11 | C2_dom, PLipase_C_PInositol-sp_X_dom, PI-PLC_fam |
| SCN2A | Ion channel | yes | IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom | |
| ALDH16A1 | Other/Unknown | no | Aldehyde_DH, Aldehyde_DH_dom, Ald_DH/histidinol_DH | |
| AKT1S1 | Other/Unknown | no | AKT1S1, PRAS_NT | |
| PTOV1-AS2 | Other/Unknown | no | ||
| PLCB4 | Enzyme (other) | yes | 3.1.4.11 | C2_dom, PLipase_C_PInositol-sp_X_dom, PI-PLC_fam |
| PNKP | Phosphatase | yes | 2.7.1.78 | HAD-SF_hydro_IIIA, PNKP, Polynucleotide_phosphatase |
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) | 0 |
| broad (>20) | 7 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| granulocyte | 3 |
| Brodmann (1909) area 23 | 2 |
| parotid gland | 2 |
| right uterine tube | 2 |
| endothelial cell | 1 |
| superior frontal gyrus | 1 |
| cerebellar vermis | 1 |
| middle temporal gyrus | 1 |
| mucosa of transverse colon | 1 |
| spleen | 1 |
| gastrocnemius | 1 |
| hindlimb stylopod muscle | 1 |
| muscle of leg | 1 |
| lateral nuclear group of thalamus | 1 |
| sural nerve | 1 |
| right adrenal gland cortex | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| PLCB1 | 278 | ubiquitous | marker | endothelial cell, Brodmann (1909) area 23, superior frontal gyrus |
| SCN2A | 187 | broad | marker | middle temporal gyrus, Brodmann (1909) area 23, cerebellar vermis |
| ALDH16A1 | 212 | ubiquitous | marker | granulocyte, spleen, mucosa of transverse colon |
| AKT1S1 | 222 | ubiquitous | marker | gastrocnemius, hindlimb stylopod muscle, muscle of leg |
| PTOV1-AS2 | 247 | yes | granulocyte, parotid gland, right uterine tube | |
| PLCB4 | 273 | ubiquitous | marker | parotid gland, lateral nuclear group of thalamus, sural nerve |
| PNKP | 259 | ubiquitous | marker | right uterine tube, granulocyte, right adrenal gland cortex |
Protein interactions among cohort
Intra-cohort edges: 1.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| ALDH16A1 | 3,339 |
| SCN2A | 2,810 |
| PNKP | 2,445 |
| PLCB1 | 2,235 |
| AKT1S1 | 1,894 |
| PLCB4 | 1,595 |
| PTOV1-AS2 | 0 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| PLCB1 | PNKP | string_interaction |
Structural data
PDB: 3 · AlphaFold-only: 3 · No structure: 1
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| SCN2A | Q99250 | 5 |
| AKT1S1 | Q96B36 | 4 |
| PNKP | Q96T60 | 2 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| ALDH16A1 | Q8IZ83 | 91.58 |
| PLCB4 | Q15147 | 86.03 |
| PLCB1 | Q9NQ66 | 84.55 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 34. Enrichment computed across 7 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Synthesis of IP3 and IP4 in the cytosol | 2 | 169.2× | 0.002 | PLCB1, PLCB4 |
| PLC beta mediated events | 2 | 106.2× | 0.002 | PLCB1, PLCB4 |
| APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway | 1 | 326.3× | 0.024 | PNKP |
| Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion | 1 | 285.5× | 0.024 | PLCB1 |
| G alpha (q) signalling events | 2 | 22.9× | 0.024 | PLCB1, PLCB4 |
| Acetylcholine regulates insulin secretion | 1 | 228.4× | 0.025 | PLCB1 |
| AKT phosphorylates targets in the cytosol | 1 | 163.1× | 0.030 | AKT1S1 |
| G beta:gamma signalling through PLC beta | 1 | 114.2× | 0.031 | PLCB1 |
| Presynaptic function of Kainate receptors | 1 | 108.8× | 0.031 | PLCB1 |
| mTORC1-mediated signalling | 1 | 95.2× | 0.031 | AKT1S1 |
| Constitutive Signaling by AKT1 E17K in Cancer | 1 | 84.6× | 0.031 | AKT1S1 |
| Cellular response to heat stress | 1 | 78.8× | 0.031 | AKT1S1 |
| PI3K/AKT Signaling in Cancer | 1 | 73.7× | 0.031 | AKT1S1 |
| Interaction between L1 and Ankyrins | 1 | 73.7× | 0.031 | SCN2A |
| Phase 0 - rapid depolarisation | 1 | 69.2× | 0.031 | SCN2A |
| Sensory perception of taste | 1 | 67.2× | 0.031 | SCN2A |
| HSF1-dependent transactivation | 1 | 63.4× | 0.031 | AKT1S1 |
| Sensory perception of sweet, bitter, and umami (glutamate) taste | 1 | 55.7× | 0.033 | SCN2A |
| MTOR signalling | 1 | 53.1× | 0.033 | AKT1S1 |
| Ca2+ pathway | 1 | 35.7× | 0.047 | PLCB1 |
| L1CAM interactions | 1 | 24.0× | 0.066 | SCN2A |
| Cardiac conduction | 1 | 21.8× | 0.070 | SCN2A |
| Sensory Perception | 1 | 19.0× | 0.076 | SCN2A |
| Intracellular signaling by second messengers | 1 | 18.3× | 0.076 | AKT1S1 |
| Muscle contraction | 1 | 15.4× | 0.086 | SCN2A |
| PIP3 activates AKT signaling | 1 | 13.4× | 0.095 | AKT1S1 |
| Diseases of signal transduction by growth factor receptors and second messengers | 1 | 11.4× | 0.107 | AKT1S1 |
| Axon guidance | 1 | 9.0× | 0.129 | SCN2A |
| Nervous system development | 1 | 8.6× | 0.130 | SCN2A |
| Cellular responses to stress | 1 | 7.4× | 0.146 | AKT1S1 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| phosphatidylinositol metabolic process | 2 | 354.8× | 7e-04 | PLCB1, PLCB4 |
| phosphatidylinositol-mediated signaling | 2 | 280.9× | 7e-04 | PLCB1, PLCB4 |
| release of sequestered calcium ion into cytosol | 2 | 137.6× | 0.002 | PLCB1, PLCB4 |
| phospholipase C-activating endothelin receptor signaling pathway | 1 | 3370.4× | 0.003 | PLCB4 |
| cellular response to glyceraldehyde | 1 | 3370.4× | 0.003 | PLCB1 |
| negative regulation of monocyte extravasation | 1 | 3370.4× | 0.003 | PLCB1 |
| memory | 2 | 73.3× | 0.003 | PLCB1, SCN2A |
| intrinsic apoptotic signaling pathway in response to osmotic stress | 1 | 1685.2× | 0.004 | SCN2A |
| phosphatidylinositol catabolic process | 1 | 1685.2× | 0.004 | PLCB1 |
| activation of meiosis involved in egg activation | 1 | 1685.2× | 0.004 | PLCB1 |
| cellular response to fluoride | 1 | 1685.2× | 0.004 | PLCB1 |
| regulation of retrograde trans-synaptic signaling by endocanabinoid | 1 | 1123.5× | 0.005 | PLCB1 |
| inositol trisphosphate metabolic process | 1 | 842.6× | 0.006 | PLCB1 |
| positive regulation of developmental growth | 1 | 842.6× | 0.006 | PLCB1 |
| regulation of fertilization | 1 | 561.7× | 0.008 | PLCB1 |
| cellular response to ionomycin | 1 | 561.7× | 0.008 | PLCB1 |
| phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway | 1 | 421.3× | 0.008 | PLCB1 |
| positive regulation of glycoprotein biosynthetic process | 1 | 421.3× | 0.008 | PLCB1 |
| cellular response to vasopressin | 1 | 421.3× | 0.008 | PLCB1 |
| interleukin-12-mediated signaling pathway | 1 | 374.5× | 0.008 | PLCB1 |
| regulation of establishment of endothelial barrier | 1 | 374.5× | 0.008 | PLCB1 |
| ligand-gated ion channel signaling pathway | 1 | 374.5× | 0.008 | PLCB1 |
| interleukin-15-mediated signaling pathway | 1 | 337.0× | 0.009 | PLCB1 |
| negative regulation of cell size | 1 | 337.0× | 0.009 | AKT1S1 |
| positive regulation of acrosome reaction | 1 | 306.4× | 0.009 | PLCB1 |
| response to radiation | 1 | 240.7× | 0.011 | PNKP |
| base-excision repair, gap-filling | 1 | 224.7× | 0.011 | PNKP |
| positive regulation of embryonic development | 1 | 224.7× | 0.011 | PLCB1 |
| G protein-coupled acetylcholine receptor signaling pathway | 1 | 210.7× | 0.011 | PLCB1 |
| neurotrophin TRK receptor signaling pathway | 1 | 210.7× | 0.011 | AKT1S1 |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 6
Druggability breadth: 5 of 7 evidence-associated genes (71%) 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 |
|---|---|
| SCN2A | BEPRIDIL |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| SCN2A | 99 | 4 |
| PLCB1 | 0 | 0 |
| ALDH16A1 | 0 | 0 |
| AKT1S1 | 0 | 0 |
| PTOV1-AS2 | 0 | 0 |
| PLCB4 | 0 | 0 |
| PNKP | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| 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 |
| NIFEDIPINE | 4 | SCN2A |
| PRAZOSIN | 4 | SCN2A |
| DILTIAZEM | 4 | SCN2A |
| PRENYLAMINE | 4 | SCN2A |
| COCAINE | 4 | SCN2A |
| TRIFLUOPERAZINE | 4 | SCN2A |
| CINNARIZINE | 4 | SCN2A |
| THIORIDAZINE | 4 | SCN2A |
| ETIDOCAINE | 4 | SCN2A |
| CHLORPHENIRAMINE | 4 | SCN2A |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 3.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| SCN2A | 203 | Binding:172, Functional:20, ADMET:10, Toxicity:1 |
| AKT1S1 | 14 | Binding:14 |
| PLCB1 | 11 | Binding:9, Functional:2 |
| PNKP | 8 | Binding:8 |
| ALDH16A1 | 3 | Binding:3 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| PLCB1 | 3.1.4.11 | phosphoinositide phospholipase C |
| PLCB4 | 3.1.4.11 | phosphoinositide phospholipase C |
| PNKP | 2.7.1.78, 3.1.3.32 | polynucleotide 5’-hydroxyl-kinase, polynucleotide 3’-phosphatase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| SCN2A | 203 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 6; 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) |
|---|---|---|
| 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 |
| NIFEDIPINE | 4 | SCN2A |
| PRAZOSIN | 4 | SCN2A |
| DILTIAZEM | 4 | SCN2A |
| PRENYLAMINE | 4 | SCN2A |
| COCAINE | 4 | SCN2A |
| TRIFLUOPERAZINE | 4 | SCN2A |
| CINNARIZINE | 4 | SCN2A |
| THIORIDAZINE | 4 | SCN2A |
| ETIDOCAINE | 4 | SCN2A |
| CHLORPHENIRAMINE | 4 | SCN2A |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | SCN2A |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | PNKP |
| D | Druggable family + AlphaFold only, no drug | 2 | PLCB1, PLCB4 |
| E | Difficult family or no structure, no drug | 3 | ALDH16A1, AKT1S1, PTOV1-AS2 |
Undrugged target profiles
6 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| PLCB1 | 11 | — |
| ALDH16A1 | 3 | — |
| AKT1S1 | 14 | — |
| PTOV1-AS2 | 0 | — |
| PLCB4 | 0 | — |
| PNKP | 8 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.