TRAK1

Chr 3AR

trafficking kinesin protein 1

Also known as: DEE68, EIEE68, MILT1, OIP106

NCBI Gene: 22906 ENSG00000182606 UniProt: Q9UPV9 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 68MIM #618201

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Developmental and epileptic encephalopathy 68; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.52

LOEUF

Multiple*

Mechanism· predicted

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 OE?0.33 (0.22–0.52)

0≤0.351.4

Missense OE?0.87 (0.81–0.94)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 14 / 42.2Missense obs/exp: 516 / 590.8Syn Z: -1.14

Background carrier burden — how many people carry a rare variant somewhere in TRAK1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 31

1,485 rare PASS variants

Rare truncating (LoF)

1 in 560

135 rare PASS variants

Rare synonymous (reference)

1 in 55

669 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRAK1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 46	1 in 490
South Asian	~43k	1 in 39	1 in 1,300
Remaining (unassigned)	~30k	1 in 27	1 in 1,000
European (Finnish)	~27k	1 in 150	1 in 2,200
Admixed American	~22k	1 in 30	1 in 1,300
African / African American	~21k	1 in 25	1 in 660
East Asian	~20k	1 in 36	1 in 3,300
Ashkenazi Jewish	~13k	1 in 140	1 in 1,500
Middle Eastern	~2,884	1 in 41	≈ 1 in 1,300

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 16 coding exons well covered in gnomAD exomes and genomes.? see exons ↓