Developmental and epileptic encephalopathy 116

disease

On this page

Summary

Developmental and epileptic encephalopathy 116 (MONDO:0970945) is a disease caused by GLUL (GenCC Strong), with 2 cohort genes.

At a glance

Causal gene: GLUL (GenCC Strong)
Cohort genes: 2
ClinVar variants: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy 116
Mondo ID	MONDO:0970945
OMIM	620806
DOID	DOID:0070545
UMLS	C5935615
MedGen	1857742
GARD	0027088
Is cancer (heuristic)	no

Data availability: 18 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 116

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

18 retrieved; paginated sample, class counts are floors:

8 pathogenic, 4 likely pathogenic, 3 pathogenic/likely pathogenic, 2 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
157797	NM_018136.5(ASPM):c.2791C>T (p.Arg931Ter)	ASPM	Pathogenic	criteria provided, multiple submitters, no conflicts
157854	NM_018136.5(ASPM):c.637del (p.Ile213fs)	ASPM	Pathogenic	criteria provided, multiple submitters, no conflicts
234465	NM_018136.5(ASPM):c.1154_1155del (p.Glu385fs)	ASPM	Pathogenic	criteria provided, multiple submitters, no conflicts
4689826	NM_018136.5(ASPM):c.4174C>T (p.Arg1392Ter)	ASPM	Pathogenic	criteria provided, multiple submitters, no conflicts
4813828	NM_018136.5(ASPM):c.4119_4122del (p.Tyr1372_Tyr1373insTer)	ASPM	Pathogenic	criteria provided, single submitter
4813829	NM_018136.5(ASPM):c.4063C>T (p.Gln1355Ter)	ASPM	Pathogenic	criteria provided, single submitter
995414	NM_018136.5(ASPM):c.7325_7332dup (p.Ile2445fs)	ASPM	Pathogenic	criteria provided, multiple submitters, no conflicts
1194257	NM_001033044.4(GLUL):c.1A>G (p.Met1Val)	GLUL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2672237	NM_001033044.4(GLUL):c.1A>C (p.Met1Leu)	GLUL	Pathogenic/Likely pathogenic	no assertion criteria provided
2672238	NM_001033044.4(GLUL):c.-13-1G>A	GLUL	Pathogenic/Likely pathogenic	no assertion criteria provided
430447	NM_001033044.4(GLUL):c.1A>T (p.Met1Leu)	GLUL	Pathogenic	criteria provided, single submitter
3899941	NM_001033044.4(GLUL):c.-13-1G>C	GLUL	Likely pathogenic	criteria provided, single submitter
3899942	NM_001033044.4(GLUL):c.604T>C (p.Trp202Arg)	GLUL	Likely pathogenic	criteria provided, single submitter
4277364	NM_001033044.4(GLUL):c.602A>C (p.Gln201Pro)	GLUL	Likely pathogenic	criteria provided, single submitter
4294439	NM_001033044.4(GLUL):c.2T>C (p.Met1Thr)	GLUL	Likely pathogenic	criteria provided, single submitter
1187386	NM_001033044.4(GLUL):c.-13-2A>G	GLUL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1312453	NM_001033044.4(GLUL):c.3G>A (p.Met1Ile)	GLUL	Uncertain significance	criteria provided, multiple submitters, no conflicts
3896726	NM_001033044.4(GLUL):c.488G>A (p.Cys163Tyr)	GLUL	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · 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
GLUL	Strong	Autosomal dominant	developmental and epileptic encephalopathy 116	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GLUL	Orphanet:71278	Congenital brain dysgenesis due to glutamine synthetase deficiency
ASPM	Orphanet:2512	Autosomal recessive primary microcephaly

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
GLUL	HGNC:4341	ENSG00000135821	P15104	Glutamine synthetase	gencc,clinvar
ASPM	HGNC:19048	ENSG00000066279	Q8IZT6	Abnormal spindle-like microcephaly-associated protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GLUL	Glutamine synthetase	Glutamine synthetase that catalyzes the ATP-dependent conversion of glutamate and ammonia to glutamine.
ASPM	Abnormal spindle-like microcephaly-associated protein	Involved in mitotic spindle regulation and coordination of mitotic processes.

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
Antibody/Immunoglobulin	1	14.6×	0.135
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GLUL	Enzyme (other)	yes	6.3.1.2	Gln_synth_cat_dom, Gln_synt_N, Gln_synth/guanido_kin_cat_dom
ASPM	Antibody/Immunoglobulin	yes		IQ_motif_EF-hand-BS, CH_dom, ARM-like

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
endothelial cell	1
globus pallidus	1
medial globus pallidus	1
oocyte	1
secondary oocyte	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GLUL	309	ubiquitous	marker	endothelial cell, medial globus pallidus, globus pallidus
ASPM	176	ubiquitous	marker	oocyte, ventricular zone, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GLUL	5,006
ASPM	2,949

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GLUL	P15104	12

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ASPM	Q8IZT6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 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
Astrocytic Glutamate-Glutamine Uptake And Metabolism	1	1903.3×	0.001	GLUL
Glutamate and glutamine metabolism	1	815.7×	0.001	GLUL

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
obsolete glutamine biosynthetic process	1	8426.0×	0.001	GLUL
negative regulation of asymmetric cell division	1	8426.0×	0.001	ASPM
intracellular ammonium homeostasis	1	8426.0×	0.001	GLUL
forebrain neuroblast division	1	4213.0×	0.002	ASPM
meiotic spindle assembly	1	2808.7×	0.002	ASPM
regulation of protein localization to nucleolus	1	2808.7×	0.002	GLUL
L-glutamate catabolic process	1	2106.5×	0.002	GLUL
spindle localization	1	1685.2×	0.002	ASPM
maintenance of centrosome location	1	1404.3×	0.002	ASPM
asymmetric cell division	1	1203.7×	0.002	ASPM
regulation of sprouting angiogenesis	1	1203.7×	0.002	GLUL
regulation of endothelial cell migration	1	1053.2×	0.002	GLUL
protein palmitoylation	1	936.2×	0.003	GLUL
spindle organization	1	495.6×	0.004	ASPM
regulation of meiotic cell cycle	1	383.0×	0.005	ASPM
developmental growth	1	366.4×	0.005	ASPM
neuronal stem cell population maintenance	1	337.0×	0.005	ASPM
ribosome biogenesis	1	312.1×	0.006	GLUL
positive regulation of neuroblast proliferation	1	290.6×	0.006	ASPM
positive regulation of erythrocyte differentiation	1	255.3×	0.006	GLUL
oogenesis	1	191.5×	0.008	ASPM
negative regulation of neuron differentiation	1	135.9×	0.010	ASPM
response to glucose	1	127.7×	0.011	GLUL
cerebral cortex development	1	102.8×	0.013	ASPM
cellular response to starvation	1	96.8×	0.013	GLUL
male gonad development	1	78.0×	0.015	ASPM
positive regulation of canonical Wnt signaling pathway	1	77.3×	0.015	ASPM
neuron migration	1	66.9×	0.016	ASPM
cell population proliferation	1	51.4×	0.021	GLUL
angiogenesis	1	31.2×	0.033	GLUL

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
GLUL	PREDNISOLONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GLUL	1	4
ASPM	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PREDNISOLONE	4	GLUL

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
GLUL	45	Binding:45

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GLUL	6.3.1.2	glutamine synthetase

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

1 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)
PREDNISOLONE	4	GLUL

Druggability pyramid

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

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

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)
ASPM	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: GLUL, ASPM