TRAK1

Chr 3AR

trafficking kinesin protein 1

Also known as: DEE68, EIEE68, MILT1, OIP106

NCBI Gene: 22906ENSG00000182606UniProt: Q9UPV9OMIM: 608112

TRAK1 encodes a protein that regulates endosome-to-lysosome trafficking and mitochondrial transport by forming complexes that link mitochondria to motor proteins for cellular movement. Mutations cause developmental and epileptic encephalopathy 68, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (LOEUF 0.52), suggesting that complete loss of protein function is poorly tolerated.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.521 OMIM phenotype
Clinical Summary— TRAK1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 206 VUS of 396 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.000
Z-score 4.02
OE 0.33 (0.22–0.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.09Z-score
OE missense 0.87 (0.81–0.94)
516 obs / 590.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.22–0.52)
0≤0.351.4
Missense OE0.87 (0.81–0.94)
0≤0.61.4
Synonymous OE1.09
0≤1.21.6
LoF obs/exp: 14 / 42.2Missense obs/exp: 516 / 590.8Syn Z: -1.14
DN
0.77top 25%
GOF
0.7029th %ile
LOF
0.4234th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative, gain-of-function and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median
LOF53% of P/LP variants are LoF

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

396 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic4
VUS206
Likely Benign112
Benign33
Conflicting2
11
Pathogenic
4
Likely Pathogenic
206
VUS
112
Likely Benign
33
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
6
0
11
Likely Pathogenic
3
0
1
0
4
VUS
1
191
12
2
206
Likely Benign
0
14
27
71
112
Benign
0
8
15
10
33
Conflicting
—2
Total92136183368

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TRAK1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients