Developmental and epileptic encephalopathy, 68

disease

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Also known as DEE68developmental and epileptic encephalopathy 68EIEE68EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 68

Summary

Developmental and epileptic encephalopathy, 68 (MONDO:0032598) is a disease caused by TRAK1 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: TRAK1 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 28

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental and epileptic encephalopathy, 68
Mondo ID	MONDO:0032598
OMIM	618201
DOID	DOID:0112204
UMLS	C4748688
MedGen	1648479
GARD	0016310
Is cancer (heuristic)	no

Also known as: DEE68 · developmental and epileptic encephalopathy 68 · EIEE68 · EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 68 · epileptic encephalopathy, early infantile, 68

Data availability: 28 ClinVar variants · 1 GenCC gene-disease record.

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, 68

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

28 retrieved; paginated sample, class counts are floors:

12 uncertain significance, 10 benign, 2 pathogenic, 1 benign/likely benign, 1 likely pathogenic, 1 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
590942	NM_001042646.3(TRAK1):c.287-2A>C	TRAK1	Pathogenic	no assertion criteria provided
590943	NM_001042646.3(TRAK1):c.287-2A>G	TRAK1	Pathogenic	no assertion criteria provided
590944	NM_001042646.3(TRAK1):c.1759dup (p.His587fs)	TRAK1	Pathogenic/Likely pathogenic	no assertion criteria provided
3780739	NM_001042646.3(TRAK1):c.52_62del (p.Gly18fs)	TRAK1	Likely pathogenic	criteria provided, single submitter
1031010	NM_001042646.3(TRAK1):c.2345C>T (p.Pro782Leu)	TRAK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1031011	NM_001042646.3(TRAK1):c.568G>A (p.Val190Ile)	TRAK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1381096	NM_001042646.3(TRAK1):c.212A>G (p.His71Arg)	TRAK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1388245	NM_001042646.3(TRAK1):c.920A>G (p.Glu307Gly)	TRAK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1407253	NM_001042646.3(TRAK1):c.1861G>A (p.Glu621Lys)	TRAK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1687731	NM_001042646.3(TRAK1):c.994A>G (p.Lys332Glu)	TRAK1	Uncertain significance	criteria provided, single submitter
1687732	NM_001042646.3(TRAK1):c.1957A>T (p.Thr653Ser)	TRAK1	Uncertain significance	criteria provided, single submitter
2267455	NM_001042646.3(TRAK1):c.1490C>T (p.Thr497Met)	TRAK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2437227	NM_001042646.3(TRAK1):c.2774G>T (p.Gly925Val)	TRAK1	Uncertain significance	criteria provided, single submitter
2437228	NM_001042646.3(TRAK1):c.187G>A (p.Gly63Ser)	TRAK1	Uncertain significance	criteria provided, single submitter
3068224	NM_001042646.3(TRAK1):c.2762_2763insGAA (p.Pro921_Thr922insAsn)	TRAK1	Uncertain significance	criteria provided, single submitter
590945	NM_001042646.3(TRAK1):c.986T>C (p.Leu329Pro)	TRAK1	Uncertain significance	criteria provided, single submitter
1342257	NM_001042646.3(TRAK1):c.1095A>G (p.Ser365=)	LOC129936554	Benign	criteria provided, multiple submitters, no conflicts
1342255	NM_001042646.3(TRAK1):c.364-26T>C	TRAK1	Benign	criteria provided, multiple submitters, no conflicts
1342256	NM_001042646.3(TRAK1):c.900+43G>A	TRAK1	Benign	criteria provided, multiple submitters, no conflicts
1342258	NM_001042646.3(TRAK1):c.1744+77G>A	TRAK1	Benign	criteria provided, multiple submitters, no conflicts
1342259	NM_001042646.3(TRAK1):c.1749C>T (p.Ser583=)	TRAK1	Benign	criteria provided, multiple submitters, no conflicts
1342260	NM_001042646.3(TRAK1):c.1815C>T (p.Pro605=)	TRAK1	Benign	criteria provided, multiple submitters, no conflicts
1342261	NM_001042646.3(TRAK1):c.2067-41A>G	TRAK1	Benign	criteria provided, multiple submitters, no conflicts
1342262	NM_001042646.3(TRAK1):c.2067-12T>C	TRAK1	Benign	criteria provided, multiple submitters, no conflicts
1342263	NM_001042646.3(TRAK1):c.*42CTC[1]	TRAK1	Benign	criteria provided, single submitter
1600840	NM_001042646.3(TRAK1):c.432C>T (p.Thr144=)	TRAK1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
734533	NM_001042646.3(TRAK1):c.1451C>T (p.Pro484Leu)	TRAK1	Likely benign	criteria provided, multiple submitters, no conflicts
977317	NM_001042646.3(TRAK1):c.1963+101GGA[12]	TRAK1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
TRAK1	Strong	Autosomal recessive	developmental and epileptic encephalopathy, 68	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRAK1	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
TRAK1	HGNC:29947	ENSG00000182606	Q9UPV9	Trafficking kinesin-binding protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRAK1	Trafficking kinesin-binding protein 1	Involved in the regulation of endosome-to-lysosome trafficking, including endocytic trafficking of EGF-EGFR complexes and GABA-A receptors.

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)
TRAK1	Other/Unknown	no		HAP1_N, TRAK1/2_C, Intracell_Traff-Reg

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
oocyte	1
paraflocculus	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRAK1	295	ubiquitous	marker	secondary oocyte, paraflocculus, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRAK1	976

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TRAK1	Q9UPV9	59.19

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
RHOT1 GTPase cycle	1	2284.0×	9e-04	TRAK1
RHOT2 GTPase cycle	1	1631.4×	9e-04	TRAK1
Signaling by BRAF and RAF1 fusions	1	170.4×	0.006	TRAK1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mitochondrion distribution	1	2106.5×	0.004	TRAK1
axonal transport of mitochondrion	1	1404.3×	0.004	TRAK1
vesicle transport along microtubule	1	887.0×	0.004	TRAK1
positive regulation of axonogenesis	1	581.1×	0.004	TRAK1
dendrite morphogenesis	1	432.1×	0.004	TRAK1
protein targeting	1	366.4×	0.004	TRAK1
endosome to lysosome transport	1	337.0×	0.004	TRAK1
protein O-linked glycosylation	1	224.7×	0.005	TRAK1
neurogenesis	1	208.1×	0.005	TRAK1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	TRAK1

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
TRAK1	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	TRAK1

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)
TRAK1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: TRAK1