Developmental and epileptic encephalopathy, 40

Summary

Developmental and epileptic encephalopathy, 40 (MONDO:0014895) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 40
Mondo ID	MONDO:0014895
OMIM	617065
DOID	DOID:0080427
UMLS	C4310737
MedGen	934704
GARD	0016182
Is cancer (heuristic)	no

Also known as: DEE40 · developmental and epileptic encephalopathy 40 · early infantile epileptic encephalopathy caused by mutation in GUF1 · EIEE40 · epileptic encephalopathy, early infantile, 40 · epileptic encephalopathy, early infantile, 40; EIEE40 · epileptic encephalopathy, early infantile, type 40 · GUF1 early infantile epileptic encephalopathy

Data availability: 15 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › infantile spasms › developmental and epileptic encephalopathy, 40

Related subtypes (7): developmental and epileptic encephalopathy, 2, developmental and epileptic encephalopathy, 1, developmental and epileptic encephalopathy, 5, developmental and epileptic encephalopathy, 12, developmental and epileptic encephalopathy, 15, developmental and epileptic encephalopathy, 27, developmental and epileptic encephalopathy, 30

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

15 retrieved; paginated sample, class counts are floors:

6 benign, 4 uncertain significance, 4 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
253096	NM_021927.3(GUF1):c.1825G>T (p.Ala609Ser)	GUF1	Pathogenic	no assertion criteria provided
1030775	NM_021927.3(GUF1):c.1954G>A (p.Val652Ile)	GUF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1341779	NM_021927.3(GUF1):c.1472_1476del (p.Leu491fs)	GUF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1430218	NM_021927.3(GUF1):c.1402_1403del (p.Glu468fs)	GUF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
728658	NM_021927.3(GUF1):c.514C>G (p.Gln172Glu)	GUF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030774	NM_021927.3(GUF1):c.1934A>G (p.Lys645Arg)	GUF1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2057871	NM_021927.3(GUF1):c.1250T>A (p.Leu417Gln)	GUF1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3779715	NM_021927.3(GUF1):c.1203-1G>A	GUF1	Uncertain significance	criteria provided, single submitter
809633	NM_021927.3(GUF1):c.809T>C (p.Ile270Thr)	GUF1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1285313	NM_021927.3(GUF1):c.173T>C (p.Leu58Pro)	GUF1	Benign	criteria provided, multiple submitters, no conflicts
1285314	NM_021927.3(GUF1):c.585+27C>T	GUF1	Benign	criteria provided, multiple submitters, no conflicts
1285315	NM_021927.3(GUF1):c.586-28_586-27insA	GUF1	Benign	criteria provided, single submitter
1285316	NM_021927.3(GUF1):c.586-27T>A	GUF1	Benign	criteria provided, multiple submitters, no conflicts
1285317	NM_021927.3(GUF1):c.1715+8C>G	GUF1	Benign	criteria provided, multiple submitters, no conflicts
1285318	NM_021927.3(GUF1):c.1872+23T>G	GUF1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
GUF1	Limited	Unknown	developmental and epileptic encephalopathy, 40	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GUF1	Orphanet:697160	Infantile epileptic spasms syndrome

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
GUF1	HGNC:25799	ENSG00000151806	Q8N442	Translation factor GUF1, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GUF1	Translation factor GUF1, mitochondrial	Promotes mitochondrial protein synthesis.

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)
GUF1	Other/Unknown	no		EFG_V-like, T_Tr_GTP-bd_dom, EFTu-like_2

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
gastrocnemius	1
muscle of leg	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GUF1	268	ubiquitous	marker	ventricular zone, gastrocnemius, muscle of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GUF1	3,147

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GUF1	Q8N442	81.89

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of translation	1	227.7×	0.009	GUF1
translation	1	102.8×	0.010	GUF1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
GUF1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	1	GUF1

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)
GUF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.