Developmental and epileptic encephalopathy, 11
diseaseOn this page
Also known as DEE11developmental and epileptic encephalopathy 11early infantile epileptic encephalopathy caused by mutation in SCN2AEIEE11epileptic encephalopathy, early infantile, 11epileptic encephalopathy, early infantile, type 11SCN2A early infantile epileptic encephalopathy
Summary
Developmental and epileptic encephalopathy, 11 (MONDO:0013388) is a disease caused by SCN2A (GenCC Definitive), with 5 cohort genes. The dominant Reactome pathway is Interaction between L1 and Ankyrins (3 cohort genes).
At a glance
- Causal gene: SCN2A (GenCC Definitive)
- Cohort genes: 5
- ClinVar variants: 2,028
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | developmental and epileptic encephalopathy, 11 |
| Mondo ID | MONDO:0013388 |
| OMIM | 613721 |
| DOID | DOID:0080421 |
| UMLS | C3150987 |
| MedGen | 462337 |
| GARD | 0015699 |
| Is cancer (heuristic) | no |
Also known as: DEE11 · developmental and epileptic encephalopathy 11 · early infantile epileptic encephalopathy caused by mutation in SCN2A · EIEE11 · epileptic encephalopathy, early infantile, 11 · epileptic encephalopathy, early infantile, type 11 · SCN2A early infantile epileptic encephalopathy
Data availability: 2,028 ClinVar variants · 3 GenCC gene-disease records · 3 cell lines.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neurological disease › Mendelian neurodevelopmental disorder › genetic developmental and epileptic encephalopathy › developmental and epileptic encephalopathy, 11
Related subtypes (104): developmental and epileptic encephalopathy, 9, developmental and epileptic encephalopathy, 8, developmental and epileptic encephalopathy, 2, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, developmental and epileptic encephalopathy, 1, developmental and epileptic encephalopathy, 3, developmental and epileptic encephalopathy, 4, microcephaly, seizures, and developmental delay, developmental and epileptic encephalopathy, 5, developmental and epileptic encephalopathy, 7, neonatal-onset encephalopathy with rigidity and seizures, developmental and epileptic encephalopathy, 14, developmental and epileptic encephalopathy, 15, developmental and epileptic encephalopathy, 17, developmental and epileptic encephalopathy, 18, developmental and epileptic encephalopathy, 19, developmental and epileptic encephalopathy, 23, developmental and epileptic encephalopathy, 27, developmental and epileptic encephalopathy, 30, developmental and epileptic encephalopathy, 50, developmental and epileptic encephalopathy, 35, developmental and epileptic encephalopathy, 37, developmental and epileptic encephalopathy, 38, developmental and epileptic encephalopathy, 40, developmental and epileptic encephalopathy, 48, developmental and epileptic encephalopathy, 49, developmental and epileptic encephalopathy, 51, Lennox-Gastaut syndrome, developmental and epileptic encephalopathy 91, developmental and epileptic encephalopathy 92, developmental and epileptic encephalopathy 93, developmental and epileptic encephalopathy 96, developmental and epileptic encephalopathy, 90, developmental and epileptic encephalopathy, 85, with or without midline brain defects, developmental and epileptic encephalopathy, 67, developmental and epileptic encephalopathy, 86, developmental and epileptic encephalopathy, 87, developmental and epileptic encephalopathy, 88, developmental and epileptic encephalopathy 6B, developmental and epileptic encephalopathy 97, developmental and epileptic encephalopathy 98, developmental and epileptic encephalopathy 99, developmental and epileptic encephalopathy 100, developmental and epileptic encephalopathy 101, developmental and epileptic encephalopathy 89, developmental and epileptic encephalopathy 102, developmental and epileptic encephalopathy 103, developmental and epileptic encephalopathy 104, developmental and epileptic encephalopathy 105 with hypopituitarism, developmental and epileptic encephalopathy 106, developmental and epileptic encephalopathy 107, developmental and epileptic encephalopathy, 68, developmental and epileptic encephalopathy, 69, developmental and epileptic encephalopathy, 70, developmental and epileptic encephalopathy, 71, developmental and epileptic encephalopathy, 72, developmental and epileptic encephalopathy, 74, developmental and epileptic encephalopathy, 75, developmental and epileptic encephalopathy, 76, developmental and epileptic encephalopathy, 77, developmental and epileptic encephalopathy, 78, developmental and epileptic encephalopathy, 79, developmental and epileptic encephalopathy, 80, developmental and epileptic encephalopathy, 81, developmental and epileptic encephalopathy, 82, developmental and epileptic encephalopathy, 83, developmental and epileptic encephalopathy, 84, developmental and epileptic encephalopathy, 52, developmental and epileptic encephalopathy, 53, developmental and epileptic encephalopathy, 54, developmental and epileptic encephalopathy, 55, developmental and epileptic encephalopathy, 56, developmental and epileptic encephalopathy, 57, developmental and epileptic encephalopathy, 58, developmental and epileptic encephalopathy, 59, developmental and epileptic encephalopathy, 60, developmental and epileptic encephalopathy, 61, developmental and epileptic encephalopathy, 62, developmental and epileptic encephalopathy, 63, developmental and epileptic encephalopathy, 64, developmental and epileptic encephalopathy, 65, developmental and epileptic encephalopathy, 73, developmental and epileptic encephalopathy, 66, developmental and epileptic encephalopathy, 6A, non-neonatal early infantile epileptic encephalopathy, Dravet syndrome, neonatal-onset developmental and epileptic encephalopathy, hemiplegic migraine-developmental and epileptic encephalopathy spectrum, DNM1-encephalopathy and neurodevelopmental disorder, TMEM63B-related developmental and epileptic encephalopathy with anemia, developmental and epileptic encephalopathy 108, developmental and epileptic encephalopathy 109, developmental and epileptic encephalopathy 110, developmental and epileptic encephalopathy 111, developmental and epileptic encephalopathy 112, developmental and epileptic encephalopathy 113, developmental and epileptic encephalopathy 114, developmental and epileptic encephalopathy 115, developmental and epileptic encephalopathy 116, developmental and epileptic encephalopathy 118, developmental and epileptic encephalopathy 120, developmental and epileptic encephalopathy 121, developmental and epileptic encephalopathy 119
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:
237 uncertain significance, 200 likely benign, 52 pathogenic, 36 likely pathogenic, 36 conflicting classifications of pathogenicity, 18 benign/likely benign, 16 benign, 5 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1054402 | NC_000002.11:g.(?165946660)(167168266_?)del | SCN1A | Pathogenic | criteria provided, single submitter |
| 1459193 | NC_000002.11:g.(?166210682)(167168266_?)del | SCN1A | Pathogenic | criteria provided, single submitter |
| 1000049 | NM_001040142.2(SCN2A):c.4901G>T (p.Gly1634Val) | SCN2A | Pathogenic | criteria provided, single submitter |
| 1066198 | NM_001040142.2(SCN2A):c.4551+1G>A | SCN2A | Pathogenic | criteria provided, single submitter |
| 1068258 | NM_001040142.2(SCN2A):c.4501A>G (p.Met1501Val) | SCN2A | Pathogenic | criteria provided, single submitter |
| 1070304 | NM_001040142.2(SCN2A):c.787G>A (p.Ala263Thr) | SCN2A | Pathogenic | criteria provided, single submitter |
| 1071664 | NM_001040142.2(SCN2A):c.718del (p.Ala240fs) | SCN2A | Pathogenic | criteria provided, single submitter |
| 1071677 | NM_001040142.2(SCN2A):c.1497del (p.Glu500fs) | SCN2A | Pathogenic | criteria provided, single submitter |
| 1072191 | NM_001040142.2(SCN2A):c.1267G>T (p.Val423Leu) | SCN2A | Pathogenic | criteria provided, single submitter |
| 1073234 | NM_001040142.2(SCN2A):c.4533dup (p.Pro1512fs) | SCN2A | Pathogenic | criteria provided, single submitter |
| 1074161 | NM_001040142.2(SCN2A):c.3782G>A (p.Trp1261Ter) | SCN2A | Pathogenic | criteria provided, single submitter |
| 1074300 | NM_001040142.2(SCN2A):c.4543C>T (p.Arg1515Ter) | SCN2A | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1074301 | NM_001040142.2(SCN2A):c.4787T>G (p.Ile1596Ser) | SCN2A | Pathogenic | criteria provided, single submitter |
| 1173107 | NM_001040142.2(SCN2A):c.330C>A (p.Tyr110Ter) | SCN2A | Pathogenic | criteria provided, single submitter |
| 1180439 | NM_001040142.2(SCN2A):c.986dup (p.Leu329fs) | SCN2A | Pathogenic | criteria provided, single submitter |
| 1219256 | NM_001040142.2(SCN2A):c.1729del (p.Leu577fs) | SCN2A | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1256055 | NM_001040142.2(SCN2A):c.2588C>A (p.Ser863Tyr) | SCN2A | Pathogenic | criteria provided, single submitter |
| 12876 | NM_001040142.2(SCN2A):c.3988C>T (p.Leu1330Phe) | SCN2A | Pathogenic | criteria provided, single submitter |
| 12877 | NM_001040142.2(SCN2A):c.4687C>G (p.Leu1563Val) | SCN2A | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 12878 | NM_001040142.2(SCN2A):c.2674G>A (p.Val892Ile) | SCN2A | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 12879 | NM_001040142.2(SCN2A):c.668G>A (p.Arg223Gln) | SCN2A | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 12880 | NM_001040142.2(SCN2A):c.3956G>A (p.Arg1319Gln) | SCN2A | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1318908 | NM_001040142.2(SCN2A):c.718G>T (p.Ala240Ser) | SCN2A | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1333343 | NM_001040142.2(SCN2A):c.1570C>T (p.Arg524Ter) | SCN2A | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1342674 | NM_001040142.2(SCN2A):c.4498G>A (p.Ala1500Thr) | SCN2A | Pathogenic | criteria provided, single submitter |
| 1342682 | NM_001040142.2(SCN2A):c.4712T>C (p.Ile1571Thr) | SCN2A | Pathogenic | criteria provided, single submitter |
| 1343156 | NM_001040142.2(SCN2A):c.1136G>A (p.Arg379His) | SCN2A | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1365870 | NM_001040142.2(SCN2A):c.1819_1831del (p.Arg607fs) | SCN2A | Pathogenic | criteria provided, single submitter |
| 1381138 | NM_001040142.2(SCN2A):c.3802dup (p.Val1268fs) | SCN2A | Pathogenic | criteria provided, single submitter |
| 1403875 | NM_001040142.2(SCN2A):c.1147C>T (p.Gln383Ter) | SCN2A | Pathogenic | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 16 · Orphanet: 32 · 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 |
|---|---|---|---|---|
| SCN2A | Definitive | Autosomal dominant | developmental and epileptic encephalopathy, 11 | 16 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| 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 |
| SCN1A | Orphanet:1942 | Epilepsy with myoclonic-atonic seizures |
| SCN1A | Orphanet:2382 | Lennox-Gastaut syndrome |
| SCN1A | Orphanet:293181 | Epilepsy of infancy with migrating focal seizures |
| SCN1A | Orphanet:33069 | Dravet syndrome |
| SCN1A | Orphanet:36387 | Genetic epilepsy with febrile seizure plus |
| SCN1A | Orphanet:442835 | Non-specific early-onset epileptic encephalopathy |
| SCN1A | Orphanet:569 | Familial or sporadic hemiplegic migraine |
| SCN3A | Orphanet:442835 | Non-specific early-onset epileptic encephalopathy |
| SCN3A | Orphanet:98820 | Familial focal epilepsy with variable foci |
| SHH | Orphanet:220386 | Semilobar holoprosencephaly |
| SHH | Orphanet:280195 | Septopreoptic holoprosencephaly |
| SHH | Orphanet:280200 | Microform holoprosencephaly |
| SHH | Orphanet:476119 | Autosomal dominant preaxial polydactyly-upperback hypertrichosis syndrome |
| SHH | Orphanet:485275 | Acquired schizencephaly |
| SHH | Orphanet:93321 | Isolated radial hemimelia |
| SHH | Orphanet:93336 | Polydactyly of a triphalangeal thumb |
| SHH | Orphanet:93405 | Syndactyly type 4 |
| SHH | Orphanet:93924 | Lobar holoprosencephaly |
| SHH | Orphanet:93925 | Alobar holoprosencephaly |
| SHH | Orphanet:93926 | Midline interhemispheric variant of holoprosencephaly |
| SHH | Orphanet:988 | Tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome |
| SHH | Orphanet:98938 | Colobomatous microphthalmia |
| TTC21B | Orphanet:474 | Jeune syndrome |
| TTC21B | Orphanet:93591 | Infantile nephronophthisis |
Cohort genes → proteins
5 cohort genes, 5 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 5 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| SCN2A | HGNC:10588 | ENSG00000136531 | Q99250 | Sodium channel protein type 2 subunit alpha | gencc,clinvar |
| SCN1A | HGNC:10585 | ENSG00000144285 | P35498 | Sodium channel protein type 1 subunit alpha | clinvar |
| SCN3A | HGNC:10590 | ENSG00000153253 | Q9NY46 | Sodium channel protein type 3 subunit alpha | clinvar |
| SHH | HGNC:10848 | ENSG00000164690 | Q15465 | Sonic hedgehog protein | clinvar |
| TTC21B | HGNC:25660 | ENSG00000123607 | Q7Z4L5 | Tetratricopeptide repeat protein 21B | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| SCN2A | Sodium channel protein type 2 subunit alpha | Mediates the voltage-dependent sodium ion permeability of excitable membranes. |
| SCN1A | Sodium channel protein type 1 subunit alpha | Pore-forming subunit of Nav1.1, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. |
| SCN3A | Sodium channel protein type 3 subunit alpha | Pore-forming subunit of Nav1.3, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. |
| SHH | Sonic hedgehog protein | The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity. |
| TTC21B | Tetratricopeptide repeat protein 21B | Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs). |
Protein-family classification
Druggable: 3 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.6
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 | 3 | 66.9× | 1e-05 |
| Other/Unknown | 2 | 0.7× | 0.877 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| SCN2A | Ion channel | yes | IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom | |
| SCN1A | Ion channel | yes | Na_channel_asu, Ion_trans_dom, Na_channel_a1su | |
| SCN3A | Ion channel | yes | Na_channel_asu, Ion_trans_dom, Na_trans_assoc_dom | |
| SHH | Other/Unknown | no | Hedgehog_signalling_dom, Hedgehog, Hedgehog_Hint | |
| TTC21B | Other/Unknown | no | TPR-like_helical_dom_sf, TPR_rpt, TTC21A/TTC21B |
Expression context
Cohort genes with no expression data: 0.
5 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) | 5 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| Brodmann (1909) area 23 | 2 |
| middle temporal gyrus | 2 |
| cerebellar vermis | 1 |
| lateral nuclear group of thalamus | 1 |
| primary visual cortex | 1 |
| cortical plate | 1 |
| endothelial cell | 1 |
| buccal mucosa cell | 1 |
| epithelial cell of pancreas | 1 |
| right lobe of liver | 1 |
| calcaneal tendon | 1 |
| cerebellar hemisphere | 1 |
| right uterine tube | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| SCN2A | 187 | broad | marker | middle temporal gyrus, Brodmann (1909) area 23, cerebellar vermis |
| SCN1A | 154 | tissue_specific | marker | Brodmann (1909) area 23, lateral nuclear group of thalamus, primary visual cortex |
| SCN3A | 221 | broad | marker | endothelial cell, cortical plate, middle temporal gyrus |
| SHH | 131 | broad | marker | buccal mucosa cell, right lobe of liver, epithelial cell of pancreas |
| TTC21B | 179 | ubiquitous | marker | right uterine tube, calcaneal tendon, cerebellar hemisphere |
Protein interactions among cohort
Intra-cohort edges: 2.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| SHH | 4,953 |
| SCN2A | 2,810 |
| SCN1A | 2,287 |
| TTC21B | 1,588 |
| SCN3A | 1,454 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| SCN1A | SCN2A | biogrid_interaction, string_interaction |
| SCN2A | SCN3A | intact |
Structural data
PDB: 5 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| SHH | Q15465 | 20 |
| SCN2A | Q99250 | 5 |
| TTC21B | Q7Z4L5 | 3 |
| SCN3A | Q9NY46 | 2 |
| SCN1A | P35498 | 1 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 34. Enrichment computed across 5 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 |
|---|---|---|---|---|
| Interaction between L1 and Ankyrins | 3 | 221.0× | 4e-06 | SCN2A, SCN1A, SCN3A |
| Phase 0 - rapid depolarisation | 3 | 207.6× | 4e-06 | SCN2A, SCN1A, SCN3A |
| L1CAM interactions | 3 | 72.1× | 6e-05 | SCN2A, SCN1A, SCN3A |
| Cardiac conduction | 3 | 65.3× | 6e-05 | SCN2A, SCN1A, SCN3A |
| Muscle contraction | 3 | 46.3× | 1e-04 | SCN2A, SCN1A, SCN3A |
| Sensory perception of taste | 2 | 134.3× | 4e-04 | SCN2A, SCN3A |
| Sensory perception of sweet, bitter, and umami (glutamate) taste | 2 | 111.4× | 4e-04 | SCN2A, SCN3A |
| Axon guidance | 3 | 27.1× | 4e-04 | SCN2A, SCN1A, SCN3A |
| Nervous system development | 3 | 25.8× | 4e-04 | SCN2A, SCN1A, SCN3A |
| Developmental Biology | 4 | 11.6× | 4e-04 | SCN2A, SCN1A, SCN3A, SHH |
| Sensory Perception | 2 | 38.1× | 0.003 | SCN2A, SCN3A |
| HHAT G278V doesn’t palmitoylate Hh-Np | 1 | 456.8× | 0.006 | SHH |
| Formation of lateral plate mesoderm | 1 | 456.8× | 0.006 | SHH |
| Release of Hh-Np from the secreting cell | 1 | 285.5× | 0.007 | SHH |
| Hh mutants abrogate ligand secretion | 1 | 285.5× | 0.007 | SHH |
| Ligand-receptor interactions | 1 | 285.5× | 0.007 | SHH |
| Formation of axial mesoderm | 1 | 163.1× | 0.012 | SHH |
| Activation of SMO | 1 | 126.9× | 0.015 | SHH |
| Developmental Lineage of Multipotent Pancreatic Progenitor Cells | 1 | 120.2× | 0.015 | SHH |
| Developmental Lineage of Pancreatic Acinar Cells | 1 | 60.1× | 0.028 | SHH |
| Gastrulation | 1 | 51.9× | 0.031 | SHH |
| Hh mutants are degraded by ERAD | 1 | 48.6× | 0.032 | SHH |
| Developmental Cell Lineages | 1 | 44.8× | 0.033 | SHH |
| Hedgehog ligand biogenesis | 1 | 42.3× | 0.033 | SHH |
| Intraflagellar transport | 1 | 40.1× | 0.034 | TTC21B |
| Class B/2 (Secretin family receptors) | 1 | 38.1× | 0.034 | SHH |
| Signaling by Hedgehog | 1 | 36.8× | 0.034 | SHH |
| Hedgehog ‘off’ state | 1 | 35.7× | 0.034 | TTC21B |
| Hedgehog ‘on’ state | 1 | 31.7× | 0.037 | SHH |
| GPCR ligand binding | 1 | 12.8× | 0.086 | SHH |
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 |
|---|---|---|---|---|
| cardiac muscle cell action potential involved in contraction | 3 | 421.3× | 5e-06 | SCN2A, SCN1A, SCN3A |
| sodium ion transport | 3 | 163.1× | 4e-05 | SCN2A, SCN1A, SCN3A |
| sodium ion transmembrane transport | 3 | 121.8× | 7e-05 | SCN2A, SCN1A, SCN3A |
| membrane depolarization during action potential | 2 | 674.1× | 1e-04 | SCN1A, SCN3A |
| Bergmann glial cell differentiation | 2 | 612.8× | 1e-04 | SHH, TTC21B |
| neuronal action potential | 2 | 192.6× | 0.001 | SCN2A, SCN1A |
| polarity specification of anterior/posterior axis | 1 | 3370.4× | 0.003 | SHH |
| trachea morphogenesis | 1 | 3370.4× | 0.003 | SHH |
| right lung development | 1 | 3370.4× | 0.003 | SHH |
| left lung development | 1 | 3370.4× | 0.003 | SHH |
| primary prostatic bud elongation | 1 | 3370.4× | 0.003 | SHH |
| regulation of prostatic bud formation | 1 | 3370.4× | 0.003 | SHH |
| obsolete regulation of mesenchymal cell proliferation involved in prostate gland development | 1 | 3370.4× | 0.003 | SHH |
| mesenchymal smoothened signaling pathway involved in prostate gland development | 1 | 3370.4× | 0.003 | SHH |
| positive regulation of sclerotome development | 1 | 3370.4× | 0.003 | SHH |
| tracheoesophageal septum formation | 1 | 3370.4× | 0.003 | SHH |
| negative regulation of ureter smooth muscle cell differentiation | 1 | 3370.4× | 0.003 | SHH |
| positive regulation of ureter smooth muscle cell differentiation | 1 | 3370.4× | 0.003 | SHH |
| negative regulation of kidney smooth muscle cell differentiation | 1 | 3370.4× | 0.003 | SHH |
| positive regulation of kidney smooth muscle cell differentiation | 1 | 3370.4× | 0.003 | SHH |
| smoothened signaling pathway | 2 | 72.5× | 0.003 | SHH, TTC21B |
| intrinsic apoptotic signaling pathway in response to osmotic stress | 1 | 1685.2× | 0.004 | SCN2A |
| positive regulation of skeletal muscle cell proliferation | 1 | 1685.2× | 0.004 | SHH |
| intein-mediated protein splicing | 1 | 1685.2× | 0.004 | SHH |
| trunk neural crest cell migration | 1 | 1685.2× | 0.004 | SHH |
| regulation of nodal signaling pathway | 1 | 1685.2× | 0.004 | SHH |
| regulation of intraciliary retrograde transport | 1 | 1685.2× | 0.004 | TTC21B |
| positive regulation of mesenchymal cell proliferation involved in ureter development | 1 | 1685.2× | 0.004 | SHH |
| ventral midline development | 1 | 1123.5× | 0.005 | SHH |
| CD4-positive or CD8-positive, alpha-beta T cell lineage commitment | 1 | 1123.5× | 0.005 | SHH |
Therapeutics
Drug target analysis
Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 4 · Undrugged: 1
Druggability breadth: 4 of 5 evidence-associated genes (80%) 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 |
| SCN1A | MEXILETINE HYDROCHLORIDE |
| SCN3A | BEPRIDIL |
| SHH | VISMODEGIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| SCN2A | 99 | 4 |
| SCN1A | 94 | 4 |
| SCN3A | 93 | 4 |
| SHH | 1 | 4 |
| TTC21B | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| BEPRIDIL | 4 | SCN1A, SCN2A, SCN3A |
| DIBUCAINE | 4 | SCN1A, SCN2A, SCN3A |
| ARTICAINE | 4 | SCN1A, SCN2A, SCN3A |
| BUPIVACAINE | 4 | SCN1A, SCN2A, SCN3A |
| IMIPRAMINE | 4 | SCN1A, SCN2A, SCN3A |
| DROPERIDOL | 4 | SCN1A, SCN2A, SCN3A |
| DICYCLOMINE | 4 | SCN1A, SCN2A, SCN3A |
| TETRABENAZINE | 4 | SCN1A, SCN2A, SCN3A |
| PHENIRAMINE | 4 | SCN1A, SCN2A, SCN3A |
| PRILOCAINE | 4 | SCN1A, SCN2A, SCN3A |
| PROPOXYCAINE | 4 | SCN1A, SCN2A, SCN3A |
| PROPARACAINE | 4 | SCN1A, SCN2A, SCN3A |
| HEXYLCAINE | 4 | SCN1A, SCN2A, SCN3A |
| PRAMOXINE | 4 | SCN1A, SCN2A, SCN3A |
| BENOXINATE | 4 | SCN1A, SCN2A, SCN3A |
| QUINIDINE | 4 | SCN1A, SCN2A, SCN3A |
| FELODIPINE | 4 | SCN1A, SCN2A, SCN3A |
| PHENYTOIN | 4 | SCN1A, SCN2A, SCN3A |
| QUININE | 4 | SCN1A, SCN2A, SCN3A |
| NISOLDIPINE | 4 | SCN1A, SCN2A, SCN3A |
| NIFEDIPINE | 4 | SCN1A, SCN2A, SCN3A |
| PRAZOSIN | 4 | SCN1A, SCN2A, SCN3A |
| DILTIAZEM | 4 | SCN1A, SCN2A, SCN3A |
| PRENYLAMINE | 4 | SCN1A, SCN2A, SCN3A |
| COCAINE | 4 | SCN1A, SCN2A, SCN3A |
| TRIFLUOPERAZINE | 4 | SCN1A, SCN2A, SCN3A |
| CINNARIZINE | 4 | SCN1A, SCN2A, SCN3A |
| THIORIDAZINE | 4 | SCN1A, SCN2A, SCN3A |
| ETIDOCAINE | 4 | SCN1A, SCN2A, SCN3A |
| CHLORPHENIRAMINE | 4 | SCN1A, SCN2A, SCN3A |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| SCN2A | 203 | Binding:172, Functional:20, ADMET:10, Toxicity:1 |
| SCN1A | 149 | Binding:115, Functional:18, ADMET:14, Toxicity:2 |
| SCN3A | 102 | Binding:79, Functional:18, ADMET:4, Toxicity:1 |
| SHH | 27 | Binding:23, Functional:4 |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| SCN2A | 203 |
| SCN1A | 149 |
| SCN3A | 102 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 5; 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 | SCN1A, SCN2A, SCN3A |
| DIBUCAINE | 4 | SCN1A, SCN2A, SCN3A |
| ARTICAINE | 4 | SCN1A, SCN2A, SCN3A |
| BUPIVACAINE | 4 | SCN1A, SCN2A, SCN3A |
| IMIPRAMINE | 4 | SCN1A, SCN2A, SCN3A |
| DROPERIDOL | 4 | SCN1A, SCN2A, SCN3A |
| DICYCLOMINE | 4 | SCN1A, SCN2A, SCN3A |
| TETRABENAZINE | 4 | SCN1A, SCN2A, SCN3A |
| PHENIRAMINE | 4 | SCN1A, SCN2A, SCN3A |
| PRILOCAINE | 4 | SCN1A, SCN2A, SCN3A |
| PROPOXYCAINE | 4 | SCN1A, SCN2A, SCN3A |
| PROPARACAINE | 4 | SCN1A, SCN2A, SCN3A |
| HEXYLCAINE | 4 | SCN1A, SCN2A, SCN3A |
| PRAMOXINE | 4 | SCN1A, SCN2A, SCN3A |
| BENOXINATE | 4 | SCN1A, SCN2A, SCN3A |
| QUINIDINE | 4 | SCN1A, SCN2A, SCN3A |
| FELODIPINE | 4 | SCN1A, SCN2A, SCN3A |
| PHENYTOIN | 4 | SCN1A, SCN2A, SCN3A |
| QUININE | 4 | SCN1A, SCN2A, SCN3A |
| NISOLDIPINE | 4 | SCN1A, SCN2A, SCN3A |
| NIFEDIPINE | 4 | SCN1A, SCN2A, SCN3A |
| PRAZOSIN | 4 | SCN1A, SCN2A, SCN3A |
| DILTIAZEM | 4 | SCN1A, SCN2A, SCN3A |
| PRENYLAMINE | 4 | SCN1A, SCN2A, SCN3A |
| COCAINE | 4 | SCN1A, SCN2A, SCN3A |
| TRIFLUOPERAZINE | 4 | SCN1A, SCN2A, SCN3A |
| CINNARIZINE | 4 | SCN1A, SCN2A, SCN3A |
| THIORIDAZINE | 4 | SCN1A, SCN2A, SCN3A |
| ETIDOCAINE | 4 | SCN1A, SCN2A, SCN3A |
| CHLORPHENIRAMINE | 4 | SCN1A, SCN2A, SCN3A |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 4 | SCN2A, SCN1A, SCN3A, SHH |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | TTC21B |
Undrugged target profiles
1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| TTC21B | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.