Developmental and epileptic encephalopathy, 41

Summary

Developmental and epileptic encephalopathy, 41 (MONDO:0014916) is a disease caused by SLC1A2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SLC1A2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 53

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 41
Mondo ID	MONDO:0014916
OMIM	617105
DOID	DOID:0080442
UMLS	C4310717
MedGen	934684
GARD	0016190
Is cancer (heuristic)	no

Also known as: DEE41 · developmental and epileptic encephalopathy 41 · developmental and epileptic encephalopathy, 41 · early infantile epileptic encephalopathy caused by mutation in SLC1A2 · EIEE41 · epileptic encephalopathy, early infantile, 41 · epileptic encephalopathy, early infantile, 41; EIEE41 · epileptic encephalopathy, early infantile, type 41 · SLC1A2 early infantile epileptic encephalopathy

Data availability: 53 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of amino acid and other organic acid metabolism › inborn disorder of amino acid metabolism › inborn disorder of amino acid transport › undetermined early-onset epileptic encephalopathy › developmental and epileptic encephalopathy, 41

Related subtypes (15): developmental and epileptic encephalopathy, 13, developmental and epileptic encephalopathy, 21, developmental and epileptic encephalopathy, 24, developmental and epileptic encephalopathy, 25, developmental and epileptic encephalopathy, 26, developmental and epileptic encephalopathy, 28, developmental and epileptic encephalopathy, 29, developmental and epileptic encephalopathy, 31A, developmental and epileptic encephalopathy, 32, developmental and epileptic encephalopathy, 33, developmental and epileptic encephalopathy, 42, developmental and epileptic encephalopathy, 44, developmental and epileptic encephalopathy, 45, developmental and epileptic encephalopathy, 46, developmental and epileptic encephalopathy, 47

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

53 retrieved; paginated sample, class counts are floors:

28 uncertain significance, 7 benign, 7 conflicting classifications of pathogenicity, 5 likely pathogenic, 2 pathogenic, 1 benign/likely benign, 1 likely benign, 1 not provided, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
254265	NM_004171.4(SLC1A2):c.244G>C (p.Gly82Arg)	SLC1A2	Pathogenic	no assertion criteria provided
438736	NM_004171.4(SLC1A2):c.244G>A (p.Gly82Arg)	SLC1A2	Pathogenic	criteria provided, single submitter
438737	NM_004171.4(SLC1A2):c.866C>G (p.Pro289Arg)	SLC1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1802628	NM_004171.4(SLC1A2):c.689T>C (p.Ile230Thr)	SLC1A2	Likely pathogenic	criteria provided, single submitter
1803073	NM_004171.4(SLC1A2):c.872G>T (p.Gly291Val)	SLC1A2	Likely pathogenic	criteria provided, single submitter
2504082	NM_004171.4(SLC1A2):c.827T>G (p.Ile276Ser)	SLC1A2	Likely pathogenic	criteria provided, single submitter
2504083	NM_004171.4(SLC1A2):c.746del (p.Phe249fs)	SLC1A2	Likely pathogenic	criteria provided, single submitter
2504085	NM_004171.4(SLC1A2):c.1625A>G (p.His542Arg)	SLC1A2	Likely pathogenic	criteria provided, single submitter
1414351	NM_004171.4(SLC1A2):c.107G>A (p.Arg36His)	SLC1A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1424903	NM_004171.4(SLC1A2):c.344G>A (p.Arg115His)	SLC1A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1462601	NM_004171.4(SLC1A2):c.193C>T (p.Arg65Cys)	SLC1A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2037155	NM_004171.4(SLC1A2):c.777G>A (p.Met259Ile)	SLC1A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2144833	NM_004171.4(SLC1A2):c.1684G>A (p.Asp562Asn)	SLC1A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2157513	NM_004171.4(SLC1A2):c.1715G>A (p.Arg572His)	SLC1A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
254266	NM_004171.4(SLC1A2):c.254T>C (p.Leu85Pro)	SLC1A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1034056	NM_004171.4(SLC1A2):c.555T>A (p.Phe185Leu)	SLC1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1034057	NM_004171.4(SLC1A2):c.607G>A (p.Glu203Lys)	SLC1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1339083	NM_004171.4(SLC1A2):c.389T>C (p.Ile130Thr)	SLC1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1339115	NM_004171.4(SLC1A2):c.304A>G (p.Ile102Val)	SLC1A2	Uncertain significance	criteria provided, single submitter
1382592	NM_004171.4(SLC1A2):c.1225G>A (p.Ala409Thr)	SLC1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1525219	NM_004171.4(SLC1A2):c.353C>T (p.Thr118Met)	SLC1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1679603	NM_004171.4(SLC1A2):c.877G>A (p.Ala293Thr)	SLC1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1711859	NM_004171.4(SLC1A2):c.1079G>C (p.Gly360Ala)	SLC1A2	Uncertain significance	criteria provided, single submitter
2057526	NM_004171.4(SLC1A2):c.626G>A (p.Ser209Asn)	SLC1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2431355	NM_004171.4(SLC1A2):c.758G>T (p.Gly253Val)	SLC1A2	Uncertain significance	criteria provided, single submitter
2435977	NM_004171.4(SLC1A2):c.260G>A (p.Arg87Lys)	SLC1A2	Uncertain significance	criteria provided, single submitter
2435978	NM_004171.4(SLC1A2):c.456G>C (p.Gln152His)	SLC1A2	Uncertain significance	criteria provided, single submitter
2435979	NM_004171.4(SLC1A2):c.1639G>A (p.Val547Ile)	SLC1A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2435980	NM_004171.4(SLC1A2):c.236C>A (p.Ala79Asp)	SLC1A2	Uncertain significance	criteria provided, single submitter
2435981	NM_004171.4(SLC1A2):c.1154_1155del (p.Val385fs)	SLC1A2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · 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
SLC1A2	Strong	Autosomal dominant	developmental and epileptic encephalopathy, 41	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC1A2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC1A2	HGNC:10940	ENSG00000110436	P43004	Excitatory amino acid transporter 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC1A2	Excitatory amino acid transporter 2	Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC1A2	Other/Unknown	no		Na-dicarboxylate_symporter, Na-dicarboxylate_symporter_CS, Na:dicarbo_symporter_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	1
endothelial cell	1
entorhinal cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC1A2	227	broad	marker	endothelial cell, entorhinal cortex, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC1A2	3,184

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC1A2	P43004	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
SLC-mediated transport of amino acids	1	2284.0×	8e-04	SLC1A2
Astrocytic Glutamate-Glutamine Uptake And Metabolism	1	1903.3×	8e-04	SLC1A2
Glutamate Neurotransmitter Release Cycle	1	456.8×	0.002	SLC1A2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
neurotransmitter reuptake	1	16852.0×	0.001	SLC1A2
L-aspartate transmembrane transport	1	8426.0×	0.001	SLC1A2
D-aspartate import across plasma membrane	1	3370.4×	0.002	SLC1A2
visual behavior	1	2808.7×	0.002	SLC1A2
L-aspartate import across plasma membrane	1	2808.7×	0.002	SLC1A2
L-glutamate import across plasma membrane	1	1872.4×	0.002	SLC1A2
glutathione biosynthetic process	1	1532.0×	0.002	SLC1A2
cellular response to cocaine	1	1296.3×	0.002	SLC1A2
transepithelial transport	1	1203.7×	0.002	SLC1A2
telencephalon development	1	991.3×	0.002	SLC1A2
response to amino acid	1	991.3×	0.002	SLC1A2
protein homotrimerization	1	991.3×	0.002	SLC1A2
L-glutamate transmembrane transport	1	802.5×	0.002	SLC1A2
adult behavior	1	468.1×	0.003	SLC1A2
positive regulation of D-glucose import across plasma membrane	1	455.5×	0.003	SLC1A2
neurotransmitter transport	1	421.3×	0.003	SLC1A2
response to wounding	1	221.7×	0.006	SLC1A2
transport across blood-brain barrier	1	179.3×	0.007	SLC1A2
monoatomic ion transport	1	156.0×	0.007	SLC1A2
multicellular organism growth	1	137.0×	0.008	SLC1A2
chemical synaptic transmission	1	77.3×	0.014	SLC1A2
response to xenobiotic stimulus	1	69.1×	0.014	SLC1A2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC1A2	2	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ASPARTIC ACID	3	SLC1A2
GLUTAMIC ACID	3	SLC1A2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC1A2	90	Binding:84, Functional:6

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

2 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)
ASPARTIC ACID	3	SLC1A2
GLUTAMIC ACID	3	SLC1A2

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	1	SLC1A2
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.