Developmental and epileptic encephalopathy, 37

disease

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Also known as DEE37developmental and epileptic encephalopathy 37early infantile epileptic encephalopathy caused by mutation in FRRS1LEIEE37epileptic encephalopathy, early infantile, 37epileptic encephalopathy, early infantile, type 37FRRS1L early infantile epileptic encephalopathy

Summary

Developmental and epileptic encephalopathy, 37 (MONDO:0014859) is a disease caused by FRRS1L (GenCC Strong), with 2 cohort genes.

At a glance

Causal gene: FRRS1L (GenCC Strong)
Cohort genes: 2
ClinVar variants: 387

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 37
Mondo ID	MONDO:0014859
OMIM	616981
DOID	DOID:0080435
UMLS	C4310770
MedGen	934737
GARD	0025027
Is cancer (heuristic)	no

Also known as: DEE37 · developmental and epileptic encephalopathy 37 · early infantile epileptic encephalopathy caused by mutation in FRRS1L · EIEE37 · epileptic encephalopathy, early infantile, 37 · epileptic encephalopathy, early infantile, 37; EIEE37 · epileptic encephalopathy, early infantile, type 37 · FRRS1L early infantile epileptic encephalopathy

Data availability: 387 ClinVar variants · 4 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, 37

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

387 retrieved; paginated sample, class counts are floors:

190 uncertain significance, 140 likely benign, 28 pathogenic, 7 pathogenic/likely pathogenic, 6 benign, 6 conflicting classifications of pathogenicity, 5 likely pathogenic, 5 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070692	NM_014334.4(FRRS1L):c.121G>T (p.Gly41Ter)	FRRS1L	Pathogenic	criteria provided, single submitter
1071396	NM_014334.4(FRRS1L):c.566del (p.Pro189fs)	FRRS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073247	NC_000009.12:g.109167267dup	FRRS1L	Pathogenic	criteria provided, single submitter
1076371	NM_014334.4(FRRS1L):c.618_619insTTTTTTTTTTNNNNNNNNNNGGGATGGTCTCGATCTCCTGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTCACCTGCAGATTT (p.Lys207delinsPhePhePheXaaXaaXaaXaaGlyTrpSerArgSerProAspLeuValIleArgProProArgProProLysValLeuGlyLeuGlnAlaTer)	FRRS1L	Pathogenic	criteria provided, single submitter
1426886	NM_014334.4(FRRS1L):c.68_69del (p.Pro23fs)	FRRS1L	Pathogenic	criteria provided, single submitter
1427697	NC_000009.12:g.109167276G>A	FRRS1L	Pathogenic	criteria provided, single submitter
1452447	NM_014334.4(FRRS1L):c.564_576del (p.Asn188fs)	FRRS1L	Pathogenic	criteria provided, single submitter
1458310	NM_014334.4(FRRS1L):c.62del (p.Thr21fs)	FRRS1L	Pathogenic	criteria provided, single submitter
1459172	NC_000009.11:g.(?111903603)(111903889_?)del	FRRS1L	Pathogenic	criteria provided, single submitter
1810245	NM_014334.4(FRRS1L):c.246dup (p.Phe83fs)	FRRS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1997044	NC_000009.12:g.109167267del	FRRS1L	Pathogenic	criteria provided, single submitter
2100471	NM_014334.4(FRRS1L):c.-35_-16del	FRRS1L	Pathogenic	criteria provided, single submitter
218151	NM_014334.4(FRRS1L):c.808C>T (p.Gln270Ter)	FRRS1L	Pathogenic	criteria provided, multiple submitters, no conflicts
218152	NM_014334.4(FRRS1L):c.692G>A (p.Trp231Ter)	FRRS1L	Pathogenic	criteria provided, single submitter
218153	NM_014334.4(FRRS1L):c.584_586del (p.Gly195del)	FRRS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
218154	NM_014334.4(FRRS1L):c.283dup (p.Ile95fs)	FRRS1L	Pathogenic	criteria provided, multiple submitters, no conflicts
2698820	NM_014334.4(FRRS1L):c.618_619insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTNNNGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTCACCTGCAGATTT (p.Lys207delinsPhePhePhePhePhePhePhePhePheXaaXaaThrSerTer)	FRRS1L	Pathogenic	criteria provided, single submitter
2704376	NM_014334.4(FRRS1L):c.542G>A (p.Trp181Ter)	FRRS1L	Pathogenic	criteria provided, single submitter
2709537	NM_014334.4(FRRS1L):c.189C>G (p.Tyr63Ter)	FRRS1L	Pathogenic	criteria provided, single submitter
3245267	NC_000009.11:g.(?111899735)(111929571_?)del	FRRS1L	Pathogenic	criteria provided, single submitter
3622710	NM_014334.4(FRRS1L):c.-23G>A	FRRS1L	Pathogenic	criteria provided, single submitter
3727968	NM_014334.4(FRRS1L):c.321del (p.Phe107fs)	FRRS1L	Pathogenic	criteria provided, single submitter
4720998	NM_014334.4(FRRS1L):c.-99del	FRRS1L	Pathogenic	criteria provided, single submitter
4721448	NM_014334.4(FRRS1L):c.327del (p.Arg108_Tyr109insTer)	FRRS1L	Pathogenic	criteria provided, single submitter
4731360	NM_014334.4(FRRS1L):c.543G>A (p.Trp181Ter)	FRRS1L	Pathogenic	criteria provided, single submitter
476302	NM_014334.4(FRRS1L):c.145del (p.Asp49fs)	FRRS1L	Pathogenic	criteria provided, single submitter
476309	NM_014334.4(FRRS1L):c.721C>T (p.Arg241Ter)	FRRS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
569279	NM_014334.4(FRRS1L):c.300_301del (p.Cys100fs)	FRRS1L	Pathogenic	criteria provided, single submitter
575860	NM_014334.4(FRRS1L):c.486C>A (p.Cys162Ter)	FRRS1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
659759	NM_014334.4(FRRS1L):c.517C>T (p.Gln173Ter)	FRRS1L	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
FRRS1L	Definitive	Autosomal recessive	genetic developmental and epileptic encephalopathy	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FRRS1L	Orphanet:725	Developmental and epileptic encephalopathy with spike-wave activation in sleep
FRRS1L	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability

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
FRRS1L	HGNC:1362	ENSG00000260230	Q9P0K9	DOMON domain-containing protein FRRS1L	gencc,clinvar
ABITRAM	HGNC:1364	ENSG00000119328	Q9NX38	Protein Abitram	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FRRS1L	DOMON domain-containing protein FRRS1L	Important modulator of glutamate signaling pathway.
ABITRAM	Protein Abitram	Actin-binding protein that regulates actin polymerization, filopodia dynamics and increases the branching of proximal dendrites of developing neurons.

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)
FRRS1L	Other/Unknown	no		DOMON_domain, FRRS1L
ABITRAM	Other/Unknown	no		Single_hybrid_motif, GCV_H/Fam206, Abitram

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
Brodmann (1909) area 23	1
middle temporal gyrus	1
orbitofrontal cortex	1
bronchial epithelial cell	1
epithelium of bronchus	1
tongue squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FRRS1L	189	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, orbitofrontal cortex
ABITRAM	287	ubiquitous	marker	bronchial epithelial cell, tongue squamous epithelium, epithelium of bronchus

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FRRS1L	1,714
ABITRAM	598

Intra-cohort edges

A	B	Sources
ABITRAM	FRRS1L	string_interaction

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FRRS1L	Q9P0K9	80.60
ABITRAM	Q9NX38	80.21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

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
regulation of AMPA glutamate receptor clustering	1	2808.7×	0.002	FRRS1L
regulation of glutamate receptor signaling pathway	1	1685.2×	0.002	FRRS1L
regulation of filopodium assembly	1	526.6×	0.004	ABITRAM
regulation of actin filament polymerization	1	290.6×	0.005	ABITRAM
regulation of synaptic transmission, glutamatergic	1	255.3×	0.005	FRRS1L
regulation of postsynaptic membrane neurotransmitter receptor levels	1	247.8×	0.005	FRRS1L
dendrite morphogenesis	1	216.1×	0.005	ABITRAM

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FRRS1L	0	0
ABITRAM	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	FRRS1L, ABITRAM

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)
FRRS1L	0	—
ABITRAM	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: FRRS1L, ABITRAM