TRAK1

trafficking kinesin protein 1

Basic information

Region (hg38): 3:42013801-42225890

Links

ENSG00000182606 ∙ NCBI:22906 ∙ OMIM:608112 ∙ HGNC:29947 ∙ Uniprot:Q9UPV9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 68	AR	General	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	Neurologic	28364549; 28940097; 29846532

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRAK1 gene.

• not provided (145 variants)
• Inborn genetic diseases (44 variants)
• Developmental and epileptic encephalopathy, 68 (21 variants)
• TRAK1-related condition (2 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRAK1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	42	11	55
missense			91	5	8	104
nonsense						0
start loss			1			1
frameshift	1					1
inframe indel					2	2
splice donor/acceptor (+/-2bp)	1					1
splice region			2	5	1	8
non coding				6	13	19
Total	2	0	94	53	34

Variants in TRAK1

This is a list of pathogenic ClinVar variants found in the TRAK1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-42087337-A-G			Uncertain significance (Mar 01, 2022)
3-42091470-A-G		not specified	Uncertain significance (Aug 11, 2023)
3-42091481-T-G			Likely benign (Aug 30, 2023)
3-42091491-G-A			Benign (Jan 16, 2024)
3-42091502-C-G		TRAK1-related disorder	Likely benign (Aug 10, 2023)
3-42091521-G-A		Inborn genetic diseases	Uncertain significance (Jan 05, 2024)
3-42091546-G-A		Inborn genetic diseases	Uncertain significance (May 03, 2023)
3-42091553-C-T			Benign/Likely benign (Jan 13, 2024)
3-42125424-G-C			Uncertain significance (Nov 01, 2022)
3-42125445-G-A			Benign (Dec 06, 2023)
3-42125448-A-G			Likely benign (Jun 01, 2022)
3-42125451-C-T			Benign (Jan 06, 2024)
3-42125503-G-A		TRAK1-related disorder	Benign/Likely benign (Dec 07, 2023)
3-42125514-C-T		TRAK1-related disorder	Likely benign (Nov 03, 2023)
3-42125515-G-A		Developmental and epileptic encephalopathy, 68	Uncertain significance (Jan 22, 2021)
3-42125538-C-G			Likely benign (May 01, 2022)
3-42125540-A-G		Developmental and epileptic encephalopathy, 68	Uncertain significance (Sep 01, 2022)
3-42125600-C-T		Inborn genetic diseases	Uncertain significance (Nov 14, 2022)
3-42125609-A-T			Uncertain significance (Feb 17, 2022)
3-42125615-G-A			Pathogenic (Nov 03, 2021)
3-42125621-A-G			Likely benign (Oct 17, 2022)
3-42125630-T-C			Benign (Nov 22, 2022)
3-42149553-A-G		TRAK1-related disorder	Likely benign (Mar 01, 2022)
3-42149555-C-T			Uncertain significance (-)
3-42160354-C-A		TRAK1-related disorder	Likely benign (Jun 27, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRAK1	protein_coding	protein_coding	ENST00000327628	16	212088

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000373	1.00	125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.09	516	591	0.873	0.0000385	6198
Missense in Polyphen		234	294.22	0.79533		3050
Synonymous	-1.14	280	257	1.09	0.0000182	1958
Loss of Function	4.02	14	42.2	0.332	0.00000224	476

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000436	0.000427
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000142	0.000141
Middle Eastern	0.0000556	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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}.
• Pathway: Vitamin D Receptor Pathway;Disease;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction (Consensus)

Recessive Scores

• pRec: 0.0927

Intolerance Scores

• loftool: 0.683
• rvis_EVS: -1.43
• rvis_percentile_EVS: 4.04

Haploinsufficiency Scores

• pHI: 0.209
• hipred: Y
• hipred_score: 0.706
• ghis: 0.505

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.954

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Trak1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); muscle phenotype

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;protein O-linked glycosylation;protein targeting;anterograde axonal transport;protein localization;endosome to lysosome transport;neurogenesis;vesicle transport along microtubule;mitochondrion distribution;dendrite morphogenesis;positive regulation of axonogenesis;anterograde axonal transport of mitochondrion
• Cellular component: nucleus;cytoplasm;mitochondrion;early endosome;cell cortex;dendrite;cytoplasmic vesicle;mitochondrial membrane;dendrite cytoplasm;axonal growth cone;perinuclear region of cytoplasm;axon cytoplasm
• Molecular function: signaling receptor binding;protein binding;myosin binding;TPR domain binding;GABA receptor binding