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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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KIF1C
kinesin family member 1C
Chromosome 17 Β· 17p13.2
NCBI Gene: 10749Ensembl: ENSG00000129250.13HGNC: HGNC:6317UniProt: O43896
71PubMed Papers
21Diseases
0Drugs
36Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingRNA bindinganterograde neuronal dense core vesicle transportmicrotubule bindingspastic ataxia 2autosomal recessive spastic ataxiahereditary spastic paraplegiaIntellectual disability
✦AI Summary

KIF1C is a kinesin-3 motor protein that mediates bidirectional microtubule-based cargo transport, functioning as both an anterograde and retrograde transporter 1. As a plus-end-directed motor, KIF1C transports diverse cargoes including dense core vesicles, organelles, and mRNAs to neuronal and cellular protrusions 12. Transport activation requires relief of KIF1C autoinhibition, achieved through binding of adaptor proteins PTPN21 and Hook3 to its stalk region, which release inhibitory interactions between the motor domain and stalk 13. KIF1C participates in mRNA localization by directly interacting with cargo through RNA-binding adaptors: APC recognizes specific 3'UTR sequences, while CNBP binds GA-rich motifs and recruits KIF1C to target mRNAs 24. Notably, KIF1C exhibits a non-canonical function in promoting dynein-driven retrograde lysosomal transport via Hook3 interaction, independent of its motor activity 56. Biallelic loss-of-function mutations in KIF1C cause Hereditary Spastic Paraplegia type SPG58 (Spastic Ataxia 2), a neurodegenerative motoneuron disease 7. Additionally, KIF1C variations have been implicated in cardiac myxoma pathogenesis through transcriptional regulation of PRKAR1A 8. These findings establish KIF1C as a multifunctional motor protein critical for neuronal function and cellular trafficking.

Sources cited
1
KIF1C is a plus-end-directed kinesin-3 motor with autoinhibition relieved by PTPN21 and Hook3 binding
PMID: 31217419
2
Hook3 recruits KIF1C for anterograde cargo transport through specific protein-protein interactions
PMID: 40312563
3
KIF1C transports APC-dependent mRNAs to cell protrusions via direct interaction with 3'UTR sequences
PMID: 34493599
4
CNBP RNA-binding protein recruits KIF1C to GA-rich mRNA sequences for transport to cell protrusions
PMID: 39982819
5
KIF1C activates dynein motor function through Hook3 adaptor in bidirectional transport
PMID: 39747486
6
KIF1C supports dynein-driven retrograde lysosomal transport independent of motor activity
PMID: 39394274
7
Biallelic KIF1C loss-of-function mutations cause Hereditary Spastic Paraplegia type SPG58
PMID: 33161238
8
KIF1C mutations are associated with left atrial myxoma through PRKAR1A transcriptional regulation
PMID: 37452081
Disease Associationsβ“˜21
spastic ataxia 2Open Targets
0.78Strong
autosomal recessive spastic ataxiaOpen Targets
0.55Moderate
hereditary spastic paraplegiaOpen Targets
0.35Weak
Abnormal central motor functionOpen Targets
0.34Weak
Intellectual disabilityOpen Targets
0.34Weak
cerebellar ataxiaOpen Targets
0.33Weak
spastic ataxiaOpen Targets
0.26Weak
genetic disorderOpen Targets
0.19Weak
microcephalyOpen Targets
0.11Weak
Immunodeficiency due to a late component of complements deficiencyOpen Targets
0.10Weak
varicella, severe recurrentOpen Targets
0.09Suggestive
immunodeficiency 28Open Targets
0.09Suggestive
Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiencyOpen Targets
0.09Suggestive
recurrent Neisseria infections due to factor D deficiencyOpen Targets
0.09Suggestive
candidiasis, familial, 4Open Targets
0.08Suggestive
Chronic mucocutaneous candidosisOpen Targets
0.08Suggestive
immunodeficiency 31BOpen Targets
0.08Suggestive
Susceptibility to viral and mycobacterial infectionsOpen Targets
0.08Suggestive
type II complement component 8 deficiencyOpen Targets
0.07Suggestive
cholelithiasisOpen Targets
0.07Suggestive
Spastic ataxia 2, autosomal recessiveUniProt
Pathogenic Variants36
NM_006612.6(KIF1C):c.2005C>T (p.Arg669Ter)Pathogenic
Spastic ataxia 2
β˜…β˜…β˜†β˜†2025β†’ Residue 669
NM_006612.6(KIF1C):c.646C>T (p.Arg216Cys)Likely pathogenic
not provided|Spastic ataxia 2
β˜…β˜…β˜†β˜†2025β†’ Residue 216
NM_006612.6(KIF1C):c.2191C>T (p.Arg731Ter)Pathogenic
Spastic ataxia 2|KIF1C-related disorder|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 731
NM_006612.6(KIF1C):c.527C>T (p.Pro176Leu)Pathogenic
not provided|Spastic ataxia 2
β˜…β˜…β˜†β˜†2025β†’ Residue 176
NM_006612.6(KIF1C):c.305G>C (p.Gly102Ala)Pathogenic
not provided
β˜…β˜…β˜†β˜†2021β†’ Residue 102
NM_006612.6(KIF1C):c.2478del (p.Ala828fs)Pathogenic
Spastic ataxia 2|not provided
β˜…β˜…β˜†β˜†2020β†’ Residue 828
NM_006612.6(KIF1C):c.328C>T (p.Arg110Ter)Pathogenic
Spastic ataxia 2
β˜…β˜†β˜†β˜†2025β†’ Residue 110
NM_006612.6(KIF1C):c.1039C>T (p.Gln347Ter)Pathogenic
Spastic ataxia 2
β˜…β˜†β˜†β˜†2025β†’ Residue 347
NM_006612.6(KIF1C):c.865-1G>ALikely pathogenic
Spastic ataxia 2
β˜…β˜†β˜†β˜†2025
NM_006612.6(KIF1C):c.941-2A>GLikely pathogenic
Spastic ataxia 2
β˜…β˜†β˜†β˜†2025
NM_006612.6(KIF1C):c.182C>A (p.Ser61Ter)Pathogenic
Spastic ataxia 2
β˜…β˜†β˜†β˜†2025β†’ Residue 61
NM_006612.6(KIF1C):c.1166-2A>TLikely pathogenic
Spastic ataxia 2
β˜…β˜†β˜†β˜†2024
NM_006612.6(KIF1C):c.2885_2895del (p.Leu962fs)Likely pathogenic
Spastic ataxia 2
β˜…β˜†β˜†β˜†2024β†’ Residue 962
NM_006612.6(KIF1C):c.505C>T (p.Arg169Trp)Likely pathogenic
Spastic ataxia 2|not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 169
NM_006612.6(KIF1C):c.41C>T (p.Pro14Leu)Likely pathogenic
Spastic ataxia 2
β˜…β˜†β˜†β˜†2024β†’ Residue 14
NM_006612.6(KIF1C):c.238del (p.Glu80fs)Pathogenic
Spastic ataxia 2
β˜…β˜†β˜†β˜†2024β†’ Residue 80
NM_006612.6(KIF1C):c.64C>T (p.Gln22Ter)Likely pathogenic
Spastic ataxia 2
β˜…β˜†β˜†β˜†2023β†’ Residue 22
NM_006612.6(KIF1C):c.647G>A (p.Arg216His)Likely pathogenic
Spastic ataxia 2
β˜…β˜†β˜†β˜†2023β†’ Residue 216
NM_006612.6(KIF1C):c.601_604del (p.Lys201fs)Pathogenic
Spastic ataxia 2
β˜…β˜†β˜†β˜†2023β†’ Residue 201
NM_006612.6(KIF1C):c.1396_1397del (p.Glu466fs)Pathogenic
Spastic ataxia 2
β˜…β˜†β˜†β˜†2023β†’ Residue 466
View on ClinVar β†—
Related Genes
PTPN21Protein interaction93%KIFBPProtein interaction89%ANKFY1Protein interaction86%BICDL1Protein interaction82%RAB6AProtein interaction79%KLC2Protein interaction75%
Tissue Expression6 tissues
Heart
100%
Lung
29%
Liver
24%
Brain
16%
Ovary
12%
Bone Marrow
2%
Gene Interaction Network
Click a node to explore
KIF1CPTPN21KIFBPANKFY1BICDL1RAB6AKLC2
PROTEIN STRUCTURE
Preparing viewer…
PDB2G1L Β· 2.60 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.61LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.49 [0.40–0.61]
RankingsWhere KIF1C stands among ~20K protein-coding genes
  • #6,640of 20,598
    Most Researched71
  • #1,651of 5,498
    Most Pathogenic Variants36
  • #4,222of 17,882
    Most Constrained (LOEUF)0.61 Β· top quartile
Genes detectedKIF1C
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Molecular basis for assembly and activation of the Hook3 - KIF1C complex-dependent transport machinery.
PMID: 40312563
EMBO Rep Β· 2025
1.00
2
Crosstalk between KIF1C and PRKAR1A in left atrial myxoma.
PMID: 37452081
Commun Biol Β· 2023
0.90
3
KIF1C activates and extends dynein movement through the FHF cargo adapter.
PMID: 39747486
Nat Struct Mol Biol Β· 2025
0.80
4
PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport.
PMID: 31217419
Nat Commun Β· 2019
0.70
5
Generation of the CRISPR/Cas9-mediated KIF1C knock-out human iPSC line HIHRSi003-A-1.
PMID: 33161238
Stem Cell Res Β· 2020
0.60