GeneBe

TRAK1

protein-coding

trafficking kinesin protein 1

Gene summary

Predicted to enable GABA receptor binding activity and myosin binding activity. Involved in endosome to lysosome transport. Located in early endosome and mitochondrion. Implicated in developmental and epileptic encephalopathy 68. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001042646.3

Inheritance

AR, AD

ClinVar variants

P:9U:221B:101

Top phenotype

Developmental and epileptic encephalopathy 68

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr3:42,013,624-42,225,890

External References & Databases

Ensembl (ENSG00000182606)NCBI Gene (22906)OMIM (608112)HGNC:29947GenCCUniProt (Q9UPV9)AlphaFoldClinVar (TRAK1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~212.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

developmental and epileptic encephalopathy, 68STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032598

Submitter: PanelApp Australia

undetermined early-onset epileptic encephalopathySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018614

Submitter: Orphanet

Clinical Genomic Database (CGD)

Developmental and epileptic encephalopathy 68AR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 28364549; 28940097; 29846532Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TRAK1 variants in ClinVar

5 Conditions Cataloged
not providedTotal: 232
Inborn genetic diseasesTotal: 154
not specifiedTotal: 68
TRAK1-related disorderTotal: 30
Developmental and epileptic encephalopathy, 68Total: 21

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001042646.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
7
clinvar
80
clinvar
2
clinvar
 89
missense
208
clinvar
15
clinvar
4
clinvar
 227
nonsense
2
clinvar
 2
start loss
1
clinvar
 1
frameshift
2
clinvar
2
clinvar
1
clinvar
 5
splice donor/acceptor (+/-2bp)
3
clinvar
2
clinvar
2
clinvar
 7
Total54221956331

Highest pathogenic variant AF is 0.000002736622

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001042646.3RefSeqNP_001036111.116MANE Select
ENST00000327628.10EnsemblENSP00000328998.516MANE Select
NM_001265608.2RefSeqNP_001252537.114Standard
NM_001265609.2RefSeqNP_001252538.113Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Vitamin D Receptor Pathway
  • Disease
  • Signaling by BRAF and RAF fusions
  • Oncogenic MAPK signaling
  • Diseases of signal transduction

Biological Process

  • regulation of transcription by RNA polymerase II
  • protein O-linked glycosylation
  • protein targeting
  • anterograde axonal transport
  • protein localization

Molecular Function

  • signaling receptor binding
  • protein binding
  • myosin binding
  • TPR domain binding
  • GABA receptor binding

Cellular Component

  • nucleus
  • cytoplasm
  • mitochondrion
  • early endosome
  • cell cortex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000327628
Coding exons
16
Length
212088
Individuals with no LoFs
125723
Homozygous LoFs
0
Heterozygous LoFs
25
Defined
125748
p
0.0000994
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.095165910.8730.00003856198
Missense (PolyPhen)234294.220.795333050
Synonymous-1.142802571.090.00001821958
Loss of Function4.021442.20.3320.00000224476

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000380.00037rare
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish00.0absent
East Asian0.0000560.000054rare
Finnish00.0absent
European (Non-Finnish)0.000140.00014rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Involved in the regulation of endosome-to-lysosome trafficking, including endocytic trafficking of EGF-EGFR complexes and GABA-A receptors (PubMed:18675823). Involved in mitochondrial motility. When O-glycosylated, abolishes mitochondrial motility. Crucial for recruiting OGT to the mitochondrial surface of neuronal processes (PubMed:24995978). TRAK1 and RHOT form an essential protein complex that links KIF5 to mitochondria for light chain-independent, anterograde transport of mitochondria (By similarity). {ECO:0000250|UniProtKB:Q960V3, ECO:0000269|PubMed:18675823, ECO:0000269|PubMed:24995978}.;

Recessive Scores

pRec
0.0927

Intolerance Scores

LoFtool
0.683
RVIS EVS
-1.43
RVIS percentile EVS
4.04

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.954

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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