Developmental and epileptic encephalopathy 96

disease

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Also known as DEE96

Summary

Developmental and epileptic encephalopathy 96 (MONDO:0023659) is a disease with 2 cohort genes.

At a glance

Cohort genes: 2
ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy 96
Mondo ID	MONDO:0023659
OMIM	619340
DOID	DOID:0070377
UMLS	C5543446
MedGen	1780167
GARD	0016445
Is cancer (heuristic)	no

Also known as: DEE96

Data availability: 12 ClinVar variants · 3 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 96

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

12 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
1120201	NM_006178.4(NSF):c.1375G>A (p.Ala459Thr)	LRRC37A2	Pathogenic	no assertion criteria provided
1120202	NM_006178.4(NSF):c.1688C>T (p.Pro563Leu)	LRRC37A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4538544	NM_006178.4(NSF):c.664G>A (p.Gly222Ser)	LRRC37A2	Pathogenic	criteria provided, single submitter
2434446	NM_006178.4(NSF):c.1688C>G (p.Pro563Arg)	LRRC37A2	Likely pathogenic	criteria provided, single submitter
4531662	NM_006178.4(NSF):c.695G>A (p.Arg232Gln)	LRRC37A2	Likely pathogenic	criteria provided, single submitter
1699024	NM_006178.4(NSF):c.1590_1592dup (p.Ser531_Asp532insSer)	NSF	Likely pathogenic	criteria provided, single submitter
3358937	NM_006178.4(NSF):c.1600A>G (p.Thr534Ala)	LRRC37A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1321305	NM_006178.4(NSF):c.1359G>A (p.Met453Ile)	LRRC37A2	Uncertain significance	criteria provided, single submitter
2500351	NM_006178.4(NSF):c.1078G>T (p.Gly360Cys)	LRRC37A2	Uncertain significance	criteria provided, single submitter
3600521	NM_006178.4(NSF):c.1909G>T (p.Gly637Cys)	LRRC37A2	Uncertain significance	criteria provided, single submitter
4277438	NM_006178.4(NSF):c.1669G>A (p.Ala557Thr)	NSF	Uncertain significance	criteria provided, single submitter
4819939	NM_006178.4(NSF):c.1805T>C (p.Val602Ala)	LRRC37A2	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
NSF	Moderate	Autosomal dominant	developmental and epileptic encephalopathy 96	3

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
NSF	HGNC:8016	ENSG00000073969	P46459	Vesicle-fusing ATPase	gencc,clinvar
LRRC37A2	HGNC:32404	ENSG00000238083	A6NM11	Leucine-rich repeat-containing protein 37A2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NSF	Vesicle-fusing ATPase	Required for vesicle-mediated transport.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NSF	Other/Unknown	no		CDC4_N-term_subdom, AAA+_ATPase, ATPase_AAA_core
LRRC37A2	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRRC37

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
prefrontal cortex	1
primary visual cortex	1
superior frontal gyrus	1
cerebellar hemisphere	1
right testis	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NSF	134	tissue_specific	marker	superior frontal gyrus, prefrontal cortex, primary visual cortex
LRRC37A2	134		yes	right uterine tube, right testis, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NSF	3,764
LRRC37A2	601

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NSF	P46459	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LRRC37A2	A6NM11	42.32

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Trafficking of GluR2-containing AMPA receptors	1	671.8×	0.009	NSF
Intra-Golgi traffic	1	259.6×	0.009	NSF
Retrograde transport at the Trans-Golgi-Network	1	219.6×	0.009	NSF
COPII-mediated vesicle transport	1	163.1×	0.009	NSF
COPI-dependent Golgi-to-ER retrograde traffic	1	110.9×	0.009	NSF
COPI-mediated anterograde transport	1	109.8×	0.009	NSF

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
SNARE complex disassembly	1	5617.3×	0.001	NSF
obsolete plasma membrane fusion	1	4213.0×	0.001	NSF
positive regulation of receptor recycling	1	1123.5×	0.003	NSF
regulation of exocytosis	1	702.2×	0.003	NSF
intra-Golgi vesicle-mediated transport	1	526.6×	0.003	NSF
Golgi to plasma membrane protein transport	1	526.6×	0.003	NSF
positive regulation of protein catabolic process	1	203.0×	0.007	NSF
potassium ion transport	1	191.5×	0.007	NSF
exocytosis	1	151.8×	0.008	NSF
vesicle-mediated transport	1	96.3×	0.011	NSF
intracellular protein transport	1	64.8×	0.015	NSF

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NSF	0	0
LRRC37A2	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
NSF	5	Binding:5

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

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	2	NSF, LRRC37A2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NSF	5	—
LRRC37A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: NSF, LRRC37A2