TRAK1

Summary

TRAK1 (trafficking kinesin protein 1, HGNC:29947) is a protein-coding gene on chromosome 3p22.1, encoding Trafficking kinesin-binding protein 1 (Q9UPV9). Involved in the regulation of endosome-to-lysosome trafficking, including endocytic trafficking of EGF-EGFR complexes and GABA-A receptors.

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.

Source: NCBI Gene 22906 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 68 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 377 total — 5 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 57
• MANE Select transcript: NM_001042646

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29947
Approved symbol	TRAK1
Name	trafficking kinesin protein 1
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	OIP106, KIAA1042, MILT1
Ensembl gene	ENSG00000182606
Ensembl biotype	protein_coding
OMIM	608112
Entrez	22906

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000327628, ENST00000341421, ENST00000396175, ENST00000418790, ENST00000427771, ENST00000449246, ENST00000469506, ENST00000484786, ENST00000487159, ENST00000613405, ENST00000672026, ENST00000673621

RefSeq mRNA: 11 — MANE Select: NM_001042646 NM_001042646, NM_001265608, NM_001265609, NM_001265610, NM_001349245, NM_001349246, NM_001349247, NM_001349248, NM_001349249, NM_001410741, NM_014965

CCDS: CCDS2695, CCDS43072, CCDS58826, CCDS74922, CCDS93249

Canonical transcript exons

ENST00000327628 — 16 exons

Exon	Start	End
ENSE00001297727	42222942	42225890
ENSE00001332168	42091357	42091560
ENSE00003463478	42194804	42194941
ENSE00003467356	42176814	42176890
ENSE00003474306	42200818	42201054
ENSE00003504263	42125420	42125614
ENSE00003531718	42184685	42184801
ENSE00003590938	42209767	42209985
ENSE00003629402	42193824	42193898
ENSE00003633264	42191558	42191636
ENSE00003641299	42193075	42193205
ENSE00003652089	42188045	42188145
ENSE00003655053	42199177	42199253
ENSE00003655244	42202436	42202752
ENSE00003678507	42219494	42219596
ENSE00003694154	42189016	42189124

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.3582 / max 286.0386, expressed in 1816 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36229	16.9478	1806
36246	4.1666	772
36242	1.7069	137
36230	1.4156	730
36240	1.2194	397
36245	0.5947	302
36243	0.5478	92
36241	0.3884	174
36231	0.2847	101
36239	0.0862	51

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.90	gold quality
paraflocculus	UBERON:0005351	97.14	gold quality
oocyte	CL:0000023	97.13	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.77	gold quality
epithelium of bronchus	UBERON:0002031	96.49	gold quality
bronchus	UBERON:0002185	96.42	gold quality
bronchial epithelial cell	CL:0002328	96.22	gold quality
pylorus	UBERON:0001166	96.22	gold quality
cervix squamous epithelium	UBERON:0006922	96.14	silver quality
right atrium auricular region	UBERON:0006631	95.89	gold quality
epithelium of nasopharynx	UBERON:0001951	95.77	gold quality
nipple	UBERON:0002030	95.73	gold quality
frontal pole	UBERON:0002795	95.53	gold quality
gastrocnemius	UBERON:0001388	95.52	gold quality
heart left ventricle	UBERON:0002084	95.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.37	gold quality
cardiac ventricle	UBERON:0002082	95.25	gold quality
muscle of leg	UBERON:0001383	95.19	gold quality
trachea	UBERON:0003126	95.19	gold quality
apex of heart	UBERON:0002098	94.96	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.66	gold quality
diaphragm	UBERON:0001103	94.44	silver quality
tongue squamous epithelium	UBERON:0006919	94.09	gold quality
ileal mucosa	UBERON:0000331	94.05	gold quality
middle temporal gyrus	UBERON:0002771	94.03	gold quality
mucosa of urinary bladder	UBERON:0001259	93.93	gold quality
cardiac atrium	UBERON:0002081	93.90	gold quality
nasal cavity mucosa	UBERON:0001826	93.87	gold quality
heart	UBERON:0000948	93.76	gold quality
hair follicle	UBERON:0002073	93.74	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	30.47
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, TCF12

miRNA regulators (miRDB)

86 targeting TRAK1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-6715A-3P	99.83	68.05	1473

Literature-anchored findings (GeneRIF, showing 16)

• GRIF-1 and OIP106 have roles in protein and/or organelle transport in excitable cells in a manner analogous to glutamate receptor-interacting-protein 1 (PMID:15644324)
• Data show that Trak1 interacts with hepatocyte-growth-factor-regulated tyrosine kinase substrate (Hrs), an essential component of the endosomal sorting and trafficking machinery. (PMID:18675823)
• TRAK1/MGb2-Ag is a promising diagnostic marker for gastric cancer and may help to detect signet-ring cell carcinoma and mucinous adenocarcinoma (PMID:18986759)
• MGb2-Ag/TRAK1 may play an important role in the development of colorectal cancer (CRC) and may be a valuable prognostic indicator of CRC. (PMID:21573901)
• The results of this study established a key role for mammalian TRAK1 proteins in axonal and dendritic targeting of mitochondria. (PMID:23395375)
• Details of a robust association of DISC1 with mitochondrial transport complexes containing TRAK1 and Miro1. (PMID:24092329)
• Data suggest that vitamin D receptor target genes (TRAK1; DUSP10, dual specificity phosphatase 10; NRIP1, nuclear receptor interacting protein 1; THBD, thrombomodulin) can be used as markers for individual’s response to vitamin D3 supplements. (PMID:24975273)
• By mapping and mutating four key sites of GlcNAc addition in hMilton1 (hMilton1Qmut), study demonstrated that Milton is the key and essential substrate through which OGT inhibits mitochondrial motility. (PMID:24995978)
• This study showed that the TRAK1 was prevalently localized in axons of hippocampal and cortical neurons. (PMID:25653102)
• This study confirms the role of TRAK1 in mitochondrial dynamics and constitutes the first report of this gene in association with a severe neurodevelopmental disorder. (PMID:28364549)
• The findings uncover a novel function of Trak1 as a regulator of mitochondrial fusion and provide evidence linking dysregulated mitochondrial dynamics to hypertonia pathogenesis. (PMID:28924745)
• Data show that the ADP-ribosylation factor 6 (Arf6)-trafficking kinesin protein 1 (trak1) promote the anterograde trafficking of mitochondria. (PMID:29992963)
• Mitochondria-adaptor TRAK1 promotes kinesin-1 driven transport in crowded environments. (PMID:32561740)
• TRAK1-Mediated Abnormality of Mitochondrial Fission Increases Seizure Susceptibility in Temporal Lobe Epilepsy. (PMID:33119838)
• Recurrent TRAK1::RAF1 Fusions in pediatric low-grade gliomas. (PMID:37399073)
• Interaction between the mitochondrial adaptor MIRO and the motor adaptor TRAK. (PMID:37949220)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	trak1a	ENSDARG00000041304
mus_musculus	Trak1	ENSMUSG00000032536
rattus_norvegicus	Trak1	ENSRNOG00000019262
drosophila_melanogaster	milt	FBGN0262872
caenorhabditis_elegans	trak-1	WBGENE00020838

Paralogs (2): TRAK2 (ENSG00000115993), HAP1 (ENSG00000173805)

Protein

Protein identifiers

Trafficking kinesin-binding protein 1 — Q9UPV9 (reviewed: Q9UPV9)

Alternative names: 106 kDa O-GlcNAc transferase-interacting protein, Protein Milton

All UniProt accessions (9): Q9UPV9, A0A087X0N0, A0A0D9SFL5, A0A0D9SGH2, A0A5F9ZH95, A0A5F9ZI06, C9JC32, F8WDH2, H7C3T3

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the regulation of endosome-to-lysosome trafficking, including endocytic trafficking of EGF-EGFR complexes and GABA-A receptors. Involved in mitochondrial motility. When O-glycosylated, abolishes mitochondrial motility. Crucial for recruiting OGT to the mitochondrial surface of neuronal processes. TRAK1 and RHOT form an essential protein complex that links KIF5 to mitochondria for light chain-independent, anterograde transport of mitochondria.

Subunit / interactions. Interacts with RHOT1 and RHOT2. Found in a complex with KIF5B, OGT, RHOT1 and RHOT2. Interacts with HGS. Interacts with GABRA1. Interacts with KIF5C. Interacts with OGT; stable interaction is not required for glycosylation of this protein by OGT. Isoform 1 interacts with OGT.

Subcellular location. Cytoplasm. Nucleus. Mitochondrion. Early endosome. Endosome. Mitochondrion membrane. Cell cortex.

Tissue specificity. High expression in spinal cord and moderate expression in all other tissues and specific brain regions examined. Expressed in all cell lines examined.

Post-translational modifications. O-glycosylated. Glycosylated by OGT; glycosylation in response to increased extracellular glucose levels is required for and leads to regulation of mitochondrial motility by OGT.

Disease relevance. Developmental and epileptic encephalopathy 68 (DEE68) [MIM:618201] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE68 is an autosomal recessive form characterized by onset of twitching and/or myoclonic jerks in infancy. The disorder progresses to refractory generalized tonic-clonic seizures, often resulting in status epilepticus, loss of developmental milestones, and early death. Other features include delayed development, axial hypotonia, spasticity of the limbs, and clonus. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal region is required for the early endosomal and mitochondrial localization.

Miscellaneous. Over-expressed in all investigated carcinomas, especially in gastric adenocarcinoma and signet-ring carcinoma and may serve as a marker of gastric cancer.

Similarity. Belongs to the milton family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UPV9-1	1, Milton1	yes
Q9UPV9-2	2
Q9UPV9-3	3

RefSeq proteins (11): NP_001036111, NP_001252537, NP_001252538, NP_001252539, NP_001336174, NP_001336175, NP_001336176, NP_001336177, NP_001336178, NP_001397670, NP_055780 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006933	HAP1_N	Domain
IPR022154	TRAK1/2_C	Domain
IPR051946	Intracell_Traff-Reg	Family

Pfam: PF04849, PF12448

UniProt features (32 total): splice variant 6, mutagenesis site 5, glycosylation site 4, region of interest 4, sequence conflict 4, modified residue 3, coiled-coil region 2, chain 1, domain 1, sequence variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UPV9-F1	59.19	0.21

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 719, 919, 537

Glycosylation sites (4): 447, 680, 719, 935

Mutagenesis-validated functional residues (5):

Position	Phenotype
447	reduced o-glycosylation of this protein.
658–672	loss of interaction with ogt, but interacts with kif5b and rhot1/2 and is able to localize to mitochondria. increased o-
829	reduced o-glycosylation of this protein; when associated with a-830.
830	reduced o-glycosylation of this protein; when associated with a-829.
938	reduced o-glycosylation of this protein.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-9013419	RHOT2 GTPase cycle
R-HSA-9013425	RHOT1 GTPase cycle

MSigDB gene sets: 331 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_LYSOSOMAL_TRANSPORT, GOBP_VESICLE_LOCALIZATION, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_PROTEIN_TARGETING, GOBP_VACUOLAR_TRANSPORT, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, MODULE_308, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, STARK_HYPPOCAMPUS_22Q11_DELETION_UP, BROWNE_HCMV_INFECTION_48HR_DN, CAIRO_HEPATOBLASTOMA_CLASSES_DN

GO Biological Process (10): regulation of transcription by RNA polymerase II (GO:0006357), protein O-linked glycosylation (GO:0006493), protein targeting (GO:0006605), endosome to lysosome transport (GO:0008333), axonal transport of mitochondrion (GO:0019896), neurogenesis (GO:0022008), vesicle transport along microtubule (GO:0047496), mitochondrion distribution (GO:0048311), dendrite morphogenesis (GO:0048813), positive regulation of axonogenesis (GO:0050772)

GO Molecular Function (4): myosin binding (GO:0017022), TPR domain binding (GO:0030911), GABA receptor binding (GO:0050811), protein binding (GO:0005515)

GO Cellular Component (14): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), early endosome (GO:0005769), cytosol (GO:0005829), cell cortex (GO:0005938), dendrite (GO:0030425), cytoplasmic vesicle (GO:0031410), mitochondrial membrane (GO:0031966), axonal growth cone (GO:0044295), perinuclear region of cytoplasm (GO:0048471), axon cytoplasm (GO:1904115), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Miro GTPase Cycle	2
Oncogenic MAPK signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	5
cellular anatomical structure	4
intracellular membrane-bounded organelle	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
glycoprotein biosynthetic process	1
establishment of protein localization	1
lysosomal transport	1
intercellular transport	1
vesicle-mediated transport	1
mitochondrion transport along microtubule	1
axonal transport	1
axon cytoplasm	1
nervous system development	1
cell differentiation	1
organelle transport along microtubule	1
vesicle cytoskeletal trafficking	1
mitochondrion localization	1
dendrite development	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axonogenesis	1
positive regulation of cell projection organization	1
positive regulation of neurogenesis	1
regulation of axonogenesis	1
cytoskeletal protein binding	1
protein domain specific binding	1
signaling receptor binding	1
binding	1
intracellular anatomical structure	1
endosome	1
cell periphery	1
neuron projection	1
dendritic tree	1
intracellular vesicle	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1
growth cone	1
axon	1

Protein interactions and networks

STRING

826 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRAK1	RHOT1	Q8IXI2	998
TRAK1	RHOT2	Q8IXI1	995
TRAK1	MFN2	O95140	937
TRAK1	NDE1	Q9NXR1	922
TRAK1	OGT	O15294	911
TRAK1	DISC1	Q9NRI5	879
TRAK1	TRAK2	O60296	858
TRAK1	PINK1	Q9BXM7	839
TRAK1	KIF5B	P33176	798
TRAK1	KIF5A	Q12840	774
TRAK1	MYO19	Q96H55	771
TRAK1	KIF5C	O60282	761
TRAK1	SNPH	O15079	748
TRAK1	MFN1	Q8IWA4	705
TRAK1	GSK3B	P49841	687

IntAct

54 interactions, top by confidence:

A	B	Type	Score
GSK3B	AXIN1	psi-mi:“MI:0914”(association)	0.980
RHOT1	TRAK1	psi-mi:“MI:0915”(physical association)	0.820
RHOT1	TRAK1	psi-mi:“MI:0403”(colocalization)	0.820
TRAK1	RHOT1	psi-mi:“MI:0914”(association)	0.820
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
TRAK1	RHOT2	psi-mi:“MI:0915”(physical association)	0.710
RHOT2	TRAK1	psi-mi:“MI:0403”(colocalization)	0.710
RHOT2	TRAK1	psi-mi:“MI:0915”(physical association)	0.710
TRAK1	KIF5A	psi-mi:“MI:0915”(physical association)	0.670
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
TRAK1	OGT	psi-mi:“MI:0914”(association)	0.620
TRAK1	OGT	psi-mi:“MI:0915”(physical association)	0.620
TRAK1	Ogt	psi-mi:“MI:0403”(colocalization)	0.610
TRAK1	Ogt	psi-mi:“MI:0915”(physical association)	0.610
Ogt	TRAK1	psi-mi:“MI:0915”(physical association)	0.610
Ogt	TRAK1	psi-mi:“MI:0403”(colocalization)	0.610
Kif5c	RHOT1	psi-mi:“MI:0914”(association)	0.580
TRAK2	OGT	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
TRAK1	MTX2	psi-mi:“MI:0914”(association)	0.530
TRAK1	KIF5B	psi-mi:“MI:0914”(association)	0.530
Kif5b	TRAK1	psi-mi:“MI:0915”(physical association)	0.500
TRAK1	CDK6	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
GSK3B	SEC16A	psi-mi:“MI:2364”(proximity)	0.420
TRAK1	SKIL	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (96): TRAK1 (Affinity Capture-MS), TRAK1 (Affinity Capture-MS), TRAK1 (Affinity Capture-MS), TRAK1 (Affinity Capture-MS), TRAK1 (Affinity Capture-MS), TRAK1 (Affinity Capture-MS), TRAK1 (Affinity Capture-Western), TRAK1 (Proximity Label-MS), TRAK1 (Proximity Label-MS), TRAK1 (Proximity Label-MS), TRAK1 (Affinity Capture-RNA), TRAK1 (Reconstituted Complex), TRAK1 (Affinity Capture-Western), TRAK1 (Affinity Capture-MS), TRAK1 (Two-hybrid)

ESM2 similar proteins: A0A1L8GUX5, A0A1L8GXY6, A0A1W2P884, A2CE83, B8A5S6, E7F5E1, F7DP49, H2MTR9, O08970, O35711, O60296, P27628, P53564, P60853, Q0VF96, Q28GJ0, Q2KJD6, Q3UIJ9, Q4V7D3, Q5BIX7, Q5R923, Q5SXA9, Q5SZL2, Q5U2Y9, Q5U4W1, Q5ZLT3, Q6AW69, Q6DIS8, Q6DJR2, Q6NRW2, Q6NXJ0, Q6P402, Q6PCQ0, Q6PD31, Q7TQE6, Q80ST9, Q86W92, Q8BMK0, Q8C8U0, Q8CFC9

Diamond homologs: O35668, O60296, P54256, P54257, Q6PD31, Q9UPV9, Q6GLX3, Q8R2H7, Q960V3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 44 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	152.3×	1e-12
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	134.3×	2e-12
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	134.3×	2e-12
Activation of BH3-only proteins	7	99.3×	2e-11
RHO GTPases activate PKNs	7	63.4×	5e-10
Intrinsic Pathway for Apoptosis	7	58.6×	8e-10
FOXO-mediated transcription	5	48.0×	6e-07
SARS-CoV-1-host interactions	7	35.1×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	59.4×	3e-07
substantia nigra development	5	49.5×	8e-06
intracellular protein localization	8	22.6×	4e-07
mitochondrion organization	5	20.5×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

377 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	2
Uncertain significance	196
Likely benign	101
Benign	32

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1319348	NM_001042646.3(TRAK1):c.286+1G>A	Pathogenic
3721550	NM_001042646.3(TRAK1):c.52_62dup (p.His21fs)	Pathogenic
521604	NM_001042646.3(TRAK1):c.1412_1413del (p.Glu471fs)	Pathogenic
590942	NM_001042646.3(TRAK1):c.287-2A>C	Pathogenic
590943	NM_001042646.3(TRAK1):c.287-2A>G	Pathogenic
3683039	NM_001042646.3(TRAK1):c.91+1G>A	Likely pathogenic
3780739	NM_001042646.3(TRAK1):c.52_62del (p.Gly18fs)	Likely pathogenic

SpliceAI

3580 predictions. Top by Δscore:

Variant	Effect	Δscore
3:42125418:A:AG	acceptor_gain	1.0000
3:42125418:AGAT:A	acceptor_gain	1.0000
3:42125419:G:GA	acceptor_gain	1.0000
3:42125419:GA:G	acceptor_gain	1.0000
3:42125419:GAT:G	acceptor_gain	1.0000
3:42125419:GATG:G	acceptor_gain	1.0000
3:42125419:GATGT:G	acceptor_gain	1.0000
3:42125610:CTTCC:C	donor_gain	1.0000
3:42125611:TTCC:T	donor_gain	1.0000
3:42125612:TCC:T	donor_gain	1.0000
3:42125613:CC:C	donor_gain	1.0000
3:42125613:CCGTA:C	donor_loss	1.0000
3:42125614:CGTA:C	donor_loss	1.0000
3:42125615:G:GG	donor_gain	1.0000
3:42125615:GTAA:G	donor_loss	1.0000
3:42125616:T:A	donor_loss	1.0000
3:42176809:TACA:T	acceptor_loss	1.0000
3:42176810:ACAGT:A	acceptor_loss	1.0000
3:42176812:A:AC	acceptor_loss	1.0000
3:42176812:A:AG	acceptor_gain	1.0000
3:42176813:G:GT	acceptor_gain	1.0000
3:42176813:GTT:G	acceptor_gain	1.0000
3:42176813:GTTT:G	acceptor_gain	1.0000
3:42176813:GTTTT:G	acceptor_gain	1.0000
3:42176887:GGAG:G	donor_gain	1.0000
3:42176888:GAG:G	donor_gain	1.0000
3:42176888:GAGG:G	donor_gain	1.0000
3:42176889:AGGT:A	donor_loss	1.0000
3:42176890:GGT:G	donor_loss	1.0000
3:42176891:G:GG	donor_gain	1.0000

AlphaMissense

6227 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:42176871:T:A	V115D	1.000
3:42176880:T:C	L118P	1.000
3:42176883:T:C	L119P	1.000
3:42184692:G:C	R124P	1.000
3:42184709:G:C	A130P	1.000
3:42184710:C:A	A130D	1.000
3:42184713:G:C	R131P	1.000
3:42184718:G:C	G133R	1.000
3:42184719:G:A	G133D	1.000
3:42184722:A:C	Q134P	1.000
3:42188055:T:C	L164P	1.000
3:42188085:T:C	L174P	1.000
3:42189093:T:C	L220P	1.000
3:42191610:T:C	L248P	1.000
3:42193114:T:C	L270P	1.000
3:42193165:T:C	L287P	1.000
3:42193168:T:C	L288P	1.000
3:42193888:T:C	L322P	1.000
3:42194805:T:C	L326P	1.000
3:42202729:T:A	L574H	1.000
3:42202729:T:C	L574P	1.000
3:42202735:T:A	I576N	1.000
3:42202735:T:G	I576S	1.000
3:42202742:G:C	K578N	1.000
3:42202742:G:T	K578N	1.000
3:42209787:T:A	W589R	1.000
3:42209787:T:C	W589R	1.000
3:42209788:G:C	W589S	1.000
3:42209789:G:C	W589C	1.000
3:42209789:G:T	W589C	1.000

dbSNP variants (sampled 300 via entrez): RS1000040194 (3:42095275 G>A,C), RS1000078637 (3:42217663 T>C), RS1000080025 (3:42131091 G>C), RS1000084083 (3:42090457 G>A), RS1000092073 (3:42095499 A>G), RS1000104787 (3:42056885 T>A), RS1000115884 (3:42161156 A>C,G), RS1000135939 (3:42056582 C>T), RS1000152774 (3:42135625 G>A), RS1000153248 (3:42174938 C>A), RS1000162997 (3:42076448 A>G,T), RS1000163956 (3:42135463 C>G,T), RS1000189202 (3:42221771 T>A), RS1000194490 (3:42113905 T>C), RS1000222073 (3:42176342 A>G)

Disease associations

OMIM: gene MIM:608112 | disease phenotypes: MIM:618201

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 68	Strong	Autosomal recessive
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

Mondo (2): developmental and epileptic encephalopathy, 68 (MONDO:0032598), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (0):

HPO phenotypes

57 total (30 of 57 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000348	High forehead
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration
HP:0001273	Abnormal corpus callosum morphology
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001315	Reduced tendon reflexes
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001371	Flexion contracture
HP:0001508	Failure to thrive

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001524_38	Visceral adipose tissue/subcutaneous adipose tissue ratio	8.000000e-06
GCST006168_17	Pulse pressure x alcohol consumption interaction (2df test)	5.000000e-33
GCST006168_42	Pulse pressure x alcohol consumption interaction (2df test)	2.000000e-30
GCST006171_9	Pulse pressure x alcohol consumption (light vs heavy) interaction (2df test)	2.000000e-11
GCST008158_122	Body mass index	8.000000e-06
GCST010320_107	PR interval	1.000000e-16
GCST010321_201	PR interval	8.000000e-16
GCST010796_3319	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_3320	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_3321	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_3322	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0004329	alcohol drinking
EFO:0005763	pulse pressure measurement
EFO:0004340	body mass index
EFO:0004462	PR interval
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
FR900359	increases phosphorylation	1
geraniol	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, increases expression	1
ochratoxin A	decreases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases expression	1
jinfukang	increases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
Troglitazone	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Formaldehyde	decreases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	decreases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Silicon Dioxide	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1
1-Butanol	affects cotreatment, increases abundance, increases expression	1
tert-Butylhydroperoxide	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E0S4	Ubigene HeLa TRAK1 KO	Cancer cell line	Female
CVCL_TT67	HAP1 TRAK1 (-) 1	Cancer cell line	Male
CVCL_XU69	HAP1 TRAK1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.