Infantile epilepsy syndrome

Summary

Infantile epilepsy syndrome (MONDO:0020071) is a disease (an umbrella term covering 9 Mondo subtypes) with 5 cohort genes.

At a glance

• Umbrella term: 9 Mondo subtypes
• Cohort genes: 5
• ClinVar variants: 48

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	infantile epilepsy syndrome
Mondo ID	MONDO:0020071
Orphanet	98258
GARD	0019436
Is cancer (heuristic)	no

Also known as: epilepsy syndrome of infancy · infantile epilepsy syndrome · infantile onset epilepsy syndrome

Data availability: 48 ClinVar variants.

Disease family

An umbrella term covering 9 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › epilepsy › epilepsy syndrome › infantile epilepsy syndrome

Related subtypes (7): adolescence-adult electroclinical syndrome, benign focal seizures of adolescence, neonatal epilepsy syndrome, childhood-onset epilepsy syndrome, neonatal/infantile epilepsy syndrome, myoclonic epilepsy, variable age epilepsy syndrome

Subtypes (9): intellectual disability, autosomal dominant 5, benign partial infantile seizures, infant epilepsy with migrant focal crisis, infantile spasms-broad thumbs syndrome, progressive myoclonic epilepsy with dystonia, infantile-onset mesial temporal lobe epilepsy with severe cognitive regression, undetermined early-onset epileptic encephalopathy, idiopathic hemiconvulsion-hemiplegia syndrome, myoclonic epilepsy in infancy

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

48 retrieved; paginated sample, class counts are floors:

28 pathogenic, 10 likely pathogenic, 5 pathogenic/likely pathogenic, 3 uncertain significance, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
984763	GRCh37/hg19 9q34.11(chr9:130412438-131423964)x1	CERCAM	Pathogenic	no assertion criteria provided
160070	NM_001032221.6(STXBP1):c.734A>G (p.His245Arg)	STXBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
191238	NM_001032221.6(STXBP1):c.874C>T (p.Arg292Cys)	STXBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
198157	NM_001032221.6(STXBP1):c.364C>T (p.Arg122Ter)	STXBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
199083	NM_001032221.6(STXBP1):c.704G>A (p.Arg235Gln)	STXBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
207417	NM_001032221.6(STXBP1):c.568C>T (p.Arg190Trp)	STXBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
207422	NM_001032221.6(STXBP1):c.703C>T (p.Arg235Ter)	STXBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
207424	NM_001032221.6(STXBP1):c.875G>A (p.Arg292His)	STXBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
207428	NM_001032221.6(STXBP1):c.1061G>A (p.Cys354Tyr)	STXBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
207429	NM_001032221.6(STXBP1):c.1099C>T (p.Arg367Ter)	STXBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
207431	NM_001032221.6(STXBP1):c.1216C>T (p.Arg406Cys)	STXBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
207440	NM_001032221.6(STXBP1):c.1651C>T (p.Arg551Cys)	STXBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
207444	NM_001032221.6(STXBP1):c.1702+1G>A	STXBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
265263	NM_001032221.6(STXBP1):c.1277T>C (p.Leu426Pro)	STXBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
279904	NM_001032221.6(STXBP1):c.1217G>A (p.Arg406His)	STXBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280467	NM_001032221.6(STXBP1):c.124T>C (p.Ser42Pro)	STXBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280844	NM_001032221.6(STXBP1):c.902+1G>C	STXBP1	Pathogenic	criteria provided, single submitter
379533	NM_001032221.6(STXBP1):c.794+5G>A	STXBP1	Pathogenic	criteria provided, single submitter
419724	NM_001032221.6(STXBP1):c.260_261dup (p.Ile88fs)	STXBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
450231	NM_001032221.6(STXBP1):c.1597del (p.Ser533fs)	STXBP1	Pathogenic	criteria provided, single submitter
488800	NM_001032221.6(STXBP1):c.170-2A>G	STXBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
503942	NM_001032221.6(STXBP1):c.1569_1570del (p.His523fs)	STXBP1	Pathogenic	criteria provided, single submitter
520745	NM_001032221.6(STXBP1):c.298del (p.Arg100fs)	STXBP1	Pathogenic	criteria provided, single submitter
546026	NM_001032221.6(STXBP1):c.685C>T (p.Gln229Ter)	STXBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
6730	NM_001032221.6(STXBP1):c.1162C>T (p.Arg388Ter)	STXBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
973268	NM_001032221.6(STXBP1):c.1381_1390dup (p.Arg464fs)	STXBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
984761	GRCh37/hg19 9q34.11(chr9:130431762-130432190)x1	STXBP1	Pathogenic	no assertion criteria provided
984762	NM_001032221.6(STXBP1):c.663+1G>C	STXBP1	Pathogenic	criteria provided, single submitter
984835	NM_001032221.6(STXBP1):c.1574del (p.Asn525fs)	STXBP1	Pathogenic	no assertion criteria provided
984865	NM_001032221.6(STXBP1):c.1654T>C (p.Cys552Arg)	STXBP1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SEMA5A	Orphanet:281	Monosomy 5p syndrome
STXBP1	Orphanet:495818	9q33.3q34.11 microdeletion syndrome
STXBP1	Orphanet:599373	STXBP1-related encephalopathy
SYNGAP1	Orphanet:1942	Epilepsy with myoclonic-atonic seizures
SYNGAP1	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
SYNGAP1	Orphanet:544254	SYNGAP1-related developmental and epileptic encephalopathy

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
SEMA5A	HGNC:10736	ENSG00000112902	Q13591	Semaphorin-5A	clinvar
STXBP1	HGNC:11444	ENSG00000136854	P61764	Syntaxin-binding protein 1	clinvar
SYNGAP1	HGNC:11497	ENSG00000197283	Q96PV0	Ras/Rap GTPase-activating protein SynGAP	clinvar
OSBPL9	HGNC:16386	ENSG00000117859	Q96SU4	Oxysterol-binding protein-related protein 9	clinvar
CERCAM	HGNC:23723	ENSG00000167123	Q5T4B2	Inactive glycosyltransferase 25 family member 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SEMA5A	Semaphorin-5A	Bifunctional axonal guidance cue regulated by sulfated proteoglycans; attractive effects result from interactions with heparan sulfate proteoglycans (HSPGs), while the inhibitory effects depend on interactions with chondroitin sulfate prot…
STXBP1	Syntaxin-binding protein 1	Participates in the regulation of synaptic vesicle docking and fusion through interaction with GTP-binding proteins.
SYNGAP1	Ras/Rap GTPase-activating protein SynGAP	Major constituent of the PSD essential for postsynaptic signaling.
OSBPL9	Oxysterol-binding protein-related protein 9	Interacts with OSBPL11 to function as lipid transfer proteins.
CERCAM	Inactive glycosyltransferase 25 family member 3	Probable cell adhesion protein involved in leukocyte transmigration across the blood-brain barrier.

Protein-family classification

Druggable: 0 · Difficult: 3 · Unknown: 2 · Druggable fraction: 0.0

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
Scaffold/PPI	3	10.4×	0.004
Other/Unknown	2	0.7×	0.877

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SEMA5A	Scaffold/PPI	no		TSP1_rpt, Semap_dom, Plexin_repeat
STXBP1	Other/Unknown	no		Sec1-like, Sec1-like_dom2, Sec1-like_sf
SYNGAP1	Scaffold/PPI	no		C2_dom, PH_domain, RasGAP_dom
OSBPL9	Scaffold/PPI	no		Oxysterol-bd, PH_domain, PH-like_dom_sf
CERCAM	Other/Unknown	no		Glyco_trans_25, Nucleotide-diphossugar_trans, Collagen_mod_GT25

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
metanephric glomerulus	1
renal glomerulus	1
stromal cell of endometrium	1
Brodmann (1909) area 23	1
lateral nuclear group of thalamus	1
middle temporal gyrus	1
adenohypophysis	1
pituitary gland	1
right uterine tube	1
calcaneal tendon	1
popliteal artery	1
right lung	1
C1 segment of cervical spinal cord	1
inferior vagus X ganglion	1
spinal cord	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SEMA5A	262	ubiquitous	marker	metanephric glomerulus, renal glomerulus, stromal cell of endometrium
STXBP1	287	ubiquitous	marker	middle temporal gyrus, lateral nuclear group of thalamus, Brodmann (1909) area 23
SYNGAP1	137	ubiquitous	marker	pituitary gland, right uterine tube, adenohypophysis
OSBPL9	288	ubiquitous	marker	calcaneal tendon, right lung, popliteal artery
CERCAM	209	ubiquitous	marker	C1 segment of cervical spinal cord, spinal cord, inferior vagus X ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STXBP1	3,003
SYNGAP1	2,175
OSBPL9	1,207
SEMA5A	1,189
CERCAM	838

Structural data

PDB: 2 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SEMA5A	Q13591	4
STXBP1	P61764	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CERCAM	Q5T4B2	89.17
OSBPL9	Q96SU4	77.10
SYNGAP1	Q96PV0	60.43

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 32. Enrichment computed across 5 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Acetylcholine Neurotransmitter Release Cycle	1	167.9×	0.036	STXBP1
Serotonin Neurotransmitter Release Cycle	1	158.6×	0.036	STXBP1
Norepinephrine Neurotransmitter Release Cycle	1	158.6×	0.036	STXBP1
GABA synthesis, release, reuptake and degradation	1	158.6×	0.036	STXBP1
Other semaphorin interactions	1	150.3×	0.036	SEMA5A
Dopamine Neurotransmitter Release Cycle	1	124.1×	0.036	STXBP1
Glutamate Neurotransmitter Release Cycle	1	114.2×	0.036	STXBP1
Synthesis of bile acids and bile salts	1	102.0×	0.036	OSBPL9
Semaphorin interactions	1	98.5×	0.036	SEMA5A
Defective B3GALTL causes PpS	1	77.2×	0.039	SEMA5A
O-glycosylation of TSR domain-containing proteins	1	75.1×	0.039	SEMA5A
Protein-protein interactions at synapses	1	66.4×	0.040	STXBP1
Regulation of insulin secretion	1	54.9×	0.041	STXBP1
Diseases associated with O-glycosylation of proteins	1	53.9×	0.041	SEMA5A
Neurexins and neuroligins	1	49.2×	0.041	STXBP1
Regulation of RAS by GAPs	1	48.4×	0.041	SYNGAP1
Integration of energy metabolism	1	43.9×	0.042	STXBP1
O-linked glycosylation	1	36.1×	0.048	SEMA5A
Diseases of glycosylation	1	32.8×	0.048	SEMA5A
MAPK1/MAPK3 signaling	1	32.8×	0.048	SYNGAP1
MAPK family signaling cascades	1	25.7×	0.058	SYNGAP1
Diseases of metabolism	1	20.1×	0.071	SEMA5A
RAF/MAP kinase cascade	1	15.3×	0.089	SYNGAP1
Axon guidance	1	11.3×	0.111	SEMA5A
Neuronal System	1	11.1×	0.111	STXBP1
Nervous system development	1	10.7×	0.111	SEMA5A
Post-translational protein modification	1	4.8×	0.228	SEMA5A
Developmental Biology	1	3.6×	0.285	SEMA5A
Disease	1	3.3×	0.301	SEMA5A
Metabolism of proteins	1	3.1×	0.305	SEMA5A

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
obsolete positive regulation of vesicle docking	1	3370.4×	0.005	STXBP1
signal clustering	1	3370.4×	0.005	SEMA5A
regulation of acrosomal vesicle exocytosis	1	3370.4×	0.005	STXBP1
neuron apoptotic process	2	74.1×	0.005	STXBP1, SYNGAP1
diencephalon development	1	1685.2×	0.007	SEMA5A
positive regulation of glutamate secretion, neurotransmission	1	1685.2×	0.007	STXBP1
axon target recognition	1	1123.5×	0.007	STXBP1
maintenance of postsynaptic specialization structure	1	1123.5×	0.007	SYNGAP1
negative regulation of neuron apoptotic process	2	44.4×	0.007	STXBP1, SYNGAP1
negative regulation of synaptic transmission, GABAergic	1	842.6×	0.007	STXBP1
presynaptic dense core vesicle exocytosis	1	842.6×	0.007	STXBP1
platelet degranulation	1	674.1×	0.008	STXBP1
developmental process involved in reproduction	1	674.1×	0.008	STXBP1
regulation of synapse structure or activity	1	561.7×	0.009	SYNGAP1
blood vessel endothelial cell proliferation involved in sprouting angiogenesis	1	481.5×	0.009	SEMA5A
positive regulation of axon extension involved in axon guidance	1	481.5×	0.009	SEMA5A
regulation of synaptic vesicle fusion to presynaptic active zone membrane	1	421.3×	0.010	STXBP1
synaptic vesicle maturation	1	374.5×	0.010	STXBP1
positive regulation of actin filament depolymerization	1	374.5×	0.010	SEMA5A
regulation of synaptic vesicle priming	1	337.0×	0.010	STXBP1
negative regulation of axon extension involved in axon guidance	1	337.0×	0.010	SEMA5A
positive regulation of mast cell degranulation	1	306.4×	0.010	STXBP1
SNARE complex assembly	1	280.9×	0.010	STXBP1
regulation of SNARE complex assembly	1	259.3×	0.010	STXBP1
positive regulation of calcium ion-dependent exocytosis	1	259.3×	0.010	STXBP1
negative regulation of axonogenesis	1	259.3×	0.010	SYNGAP1
intermembrane lipid transfer	1	240.7×	0.011	OSBPL9
regulation of long-term neuronal synaptic plasticity	1	198.3×	0.012	SYNGAP1
positive regulation of endothelial cell chemotaxis	1	198.3×	0.012	SEMA5A
axonal fasciculation	1	187.2×	0.012	SEMA5A

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 1 of 5 evidence-associated genes (20%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SEMA5A	0	0
STXBP1	0	0
SYNGAP1	0	0
OSBPL9	0	0
CERCAM	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
STXBP1	1	Binding:1

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	5	SEMA5A, STXBP1, SYNGAP1, OSBPL9, CERCAM

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SEMA5A	0	—
STXBP1	1	—
SYNGAP1	0	—
OSBPL9	0	—
CERCAM	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.