Developmental and epileptic encephalopathy, 52

Summary

Developmental and epileptic encephalopathy, 52 (MONDO:0033361) is a disease caused by SCN1B (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: SCN1B (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 77

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 52
Mondo ID	MONDO:0033361
OMIM	617350
DOID	DOID:0080455
UMLS	C4479236
MedGen	1376462
GARD	0016223
Is cancer (heuristic)	no

Also known as: DEE52 · developmental and epileptic encephalopathy 52 · EIEE52 · epileptic encephalopathy, early infantile, 52

Data availability: 77 ClinVar variants · 2 GenCC gene-disease records.

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, 52

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, developmental and epileptic encephalopathy, 11, 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, 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

77 retrieved; paginated sample, class counts are floors:

25 uncertain significance, 16 pathogenic/likely pathogenic, 12 pathogenic, 11 conflicting classifications of pathogenicity, 9 likely pathogenic, 3 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1338921	NM_001127222.2(CACNA1A):c.5335C>T (p.Arg1779Ter)	CACNA1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1398258	NM_001127222.2(CACNA1A):c.841del (p.Cys281fs)	CACNA1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1421109	NM_001127222.2(CACNA1A):c.5422G>A (p.Val1808Ile)	CACNA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1441063	NM_001127222.2(CACNA1A):c.2311A>T (p.Lys771Ter)	CACNA1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1679523	NM_001127222.2(CACNA1A):c.4519G>A (p.Ala1507Thr)	CACNA1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1679524	NM_001127222.2(CACNA1A):c.4031T>C (p.Leu1344Pro)	CACNA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1679527	NM_001127222.2(CACNA1A):c.2137G>A (p.Val713Met)	CACNA1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1679533	NM_001127222.2(CACNA1A):c.5015dup (p.Gln1673fs)	CACNA1A	Pathogenic	criteria provided, single submitter
195935	NM_001127222.2(CACNA1A):c.4174G>A (p.Val1392Met)	CACNA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
254268	NM_001127222.2(CACNA1A):c.2134G>A (p.Ala712Thr)	CACNA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
380972	NM_001127222.2(CACNA1A):c.4043G>A (p.Arg1348Gln)	CACNA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
420055	NM_001127222.2(CACNA1A):c.5393C>T (p.Ser1798Leu)	CACNA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
420945	NM_001127222.2(CACNA1A):c.4055C>T (p.Pro1352Leu)	CACNA1A	Pathogenic	criteria provided, multiple submitters, no conflicts
422063	NM_001127222.2(CACNA1A):c.4927G>A (p.Asp1643Asn)	CACNA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
449943	NM_001127222.2(CACNA1A):c.4897G>A (p.Asp1633Asn)	CACNA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
450171	NM_001127222.2(CACNA1A):c.2133C>G (p.Ile711Met)	CACNA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
545691	NM_001127222.2(CACNA1A):c.835C>T (p.Arg279Cys)	CACNA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
638582	NM_001127222.2(CACNA1A):c.4997G>C (p.Arg1666Pro)	CACNA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
835237	NM_001127222.2(CACNA1A):c.1635C>A (p.Tyr545Ter)	CACNA1A	Pathogenic	criteria provided, multiple submitters, no conflicts
8505	NM_001127222.2(CACNA1A):c.1745G>A (p.Arg582Gln)	CACNA1A	Pathogenic	criteria provided, multiple submitters, no conflicts
971813	NM_001127222.2(CACNA1A):c.4052G>A (p.Arg1351Gln)	CACNA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
976736	NM_001127222.2(CACNA1A):c.4064C>A (p.Thr1355Asn)	CACNA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
190859	NM_001037.5(SCN1B):c.253C>T (p.Arg85Cys)	SCN1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
375687	NM_001037.5(SCN1B):c.316A>T (p.Ile106Phe)	SCN1B	Pathogenic	no assertion criteria provided
60767	NM_001037.5(SCN1B):c.254G>A (p.Arg85His)	SCN1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
694617	NM_001037.5(SCN1B):c.449-2A>G	SCN1B	Pathogenic	reviewed by expert panel
694618	NM_001037.5(SCN1B):c.355T>G (p.Tyr119Asp)	SCN1B	Pathogenic	no assertion criteria provided
9252	NM_001037.5(SCN1B):c.363C>G (p.Cys121Trp)	SCN1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1679525	NM_001127222.2(CACNA1A):c.5417T>C (p.Val1806Ala)	CACNA1A	Likely pathogenic	criteria provided, single submitter
1679526	NM_001127222.2(CACNA1A):c.3948C>A (p.Asp1316Glu)	CACNA1A	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 13 · 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
SCN1B	Definitive	Autosomal recessive	genetic developmental and epileptic encephalopathy	15

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN1B	Orphanet:130	Brugada syndrome
SCN1B	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
SCN1B	Orphanet:33069	Dravet syndrome
SCN1B	Orphanet:334	Hereditary atrial fibrillation
SCN1B	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SCN1B	Orphanet:871	Hereditary progressive cardiac conduction defect
CACNA1A	Orphanet:2131	Alternating hemiplegia of childhood
CACNA1A	Orphanet:2382	Lennox-Gastaut syndrome
CACNA1A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
CACNA1A	Orphanet:569	Familial or sporadic hemiplegic migraine
CACNA1A	Orphanet:71518	Benign paroxysmal torticollis of infancy
CACNA1A	Orphanet:97	Familial paroxysmal ataxia
CACNA1A	Orphanet:98758	Spinocerebellar ataxia type 6

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCN1B	HGNC:10586	ENSG00000105711	Q07699	Sodium channel regulatory subunit beta-1	gencc,clinvar
CACNA1A	HGNC:1388	ENSG00000141837	O00555	Voltage-dependent P/Q-type calcium channel subunit alpha-1A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN1B	Sodium channel regulatory subunit beta-1	Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of excitable membranes.
CACNA1A	Voltage-dependent P/Q-type calcium channel subunit alpha-1A	Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene exp…

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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	55.8×	0.036
Antibody/Immunoglobulin	1	14.6×	0.067

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN1B	Antibody/Immunoglobulin	yes		Ig_V-set, Ig-like_fold, Na_channel_b1/b3
CACNA1A	Ion channel	yes		VDCCAlpha1, CACNA1A, Ion_trans_dom

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right hemisphere of cerebellum	2
cerebellum	1
primary visual cortex	1
cerebellar cortex	1
cerebellar hemisphere	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN1B	133	ubiquitous	marker	primary visual cortex, right hemisphere of cerebellum, cerebellum
CACNA1A	237	broad	marker	cerebellar hemisphere, right hemisphere of cerebellum, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCN1B	1,328
CACNA1A	346

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCN1B	Q07699	39
CACNA1A	O00555	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Presynaptic depolarization and calcium channel opening	1	475.8×	0.024	CACNA1A
Interaction between L1 and Ankyrins	1	184.2×	0.024	SCN1B
Phase 0 - rapid depolarisation	1	173.0×	0.024	SCN1B
Sensory perception of taste	1	167.9×	0.024	SCN1B
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	139.3×	0.024	SCN1B
Regulation of insulin secretion	1	109.8×	0.026	CACNA1A
Integration of energy metabolism	1	87.8×	0.028	CACNA1A
L1CAM interactions	1	60.1×	0.035	SCN1B
Cardiac conduction	1	54.4×	0.035	SCN1B
Sensory Perception	1	47.6×	0.036	SCN1B
Muscle contraction	1	38.6×	0.037	SCN1B
Transmission across Chemical Synapses	1	38.1×	0.037	CACNA1A
Axon guidance	1	22.6×	0.052	SCN1B
Neuronal System	1	22.1×	0.052	CACNA1A
Nervous system development	1	21.5×	0.052	SCN1B
Developmental Biology	1	7.2×	0.142	SCN1B
Metabolism	1	5.8×	0.165	CACNA1A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
corticospinal neuron axon guidance	1	8426.0×	0.003	SCN1B
membrane depolarization during Purkinje myocyte cell action potential	1	2808.7×	0.003	SCN1B
positive regulation of voltage-gated sodium channel activity	1	2808.7×	0.003	SCN1B
regulation of atrial cardiac muscle cell membrane depolarization	1	936.2×	0.004	SCN1B
cardiac conduction	1	842.6×	0.004	SCN1B
membrane depolarization during action potential	1	842.6×	0.004	SCN1B
locomotion	1	766.0×	0.004	SCN1B
neuronal action potential propagation	1	702.2×	0.004	SCN1B
membrane depolarization during cardiac muscle cell action potential	1	702.2×	0.004	SCN1B
regulation of sodium ion transmembrane transport	1	526.6×	0.005	SCN1B
response to amyloid-beta	1	495.6×	0.005	CACNA1A
positive regulation of sodium ion transport	1	421.3×	0.005	SCN1B
regulation of ventricular cardiac muscle cell membrane repolarization	1	421.3×	0.005	SCN1B
cardiac muscle cell action potential involved in contraction	1	351.1×	0.005	SCN1B
calcium ion import across plasma membrane	1	271.8×	0.007	CACNA1A
membrane depolarization	1	255.3×	0.007	SCN1B
cardiac muscle contraction	1	200.6×	0.008	SCN1B
cellular response to amyloid-beta	1	195.9×	0.008	CACNA1A
regulation of heart rate by cardiac conduction	1	187.2×	0.008	SCN1B
calcium ion transmembrane transport	1	105.3×	0.013	CACNA1A
sodium ion transmembrane transport	1	101.5×	0.013	SCN1B
modulation of chemical synaptic transmission	1	91.6×	0.013	CACNA1A
positive regulation of neuron projection development	1	68.5×	0.017	SCN1B
positive regulation of cytosolic calcium ion concentration	1	58.5×	0.019	CACNA1A
axon guidance	1	45.3×	0.024	SCN1B
chemical synaptic transmission	1	38.6×	0.027	CACNA1A
cell adhesion	1	18.7×	0.053	SCN1B

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 evidence-associated genes (100%) 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
CACNA1A	NIMODIPINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN1B	2	2
CACNA1A	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NIMODIPINE	4	CACNA1A
TACRINE	4	CACNA1A
DS-1971	2	SCN1B
PF-05089771	2	SCN1B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CACNA1A	19	Binding:18, Functional:1
SCN1B	15	Binding:7, ADMET:6, Toxicity:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

4 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)
NIMODIPINE	4	CACNA1A
TACRINE	4	CACNA1A
DS-1971	2	SCN1B
PF-05089771	2	SCN1B

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CACNA1A
B	Phased (≥1) drug, not yet approved	1	SCN1B
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.