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General Information
Name
neurodegenerative disease, KIF5-related
FlyBase ID
FBhh0000955
Disease Ontology Term
Parent Disease
OMIM
Overview

This report describes Drosophila models of neurodegenerative disease using alleles of the fly gene Khc, which encodes a kinesin heavy chain. There are three highly related genes in human, KIF5A, KIF5B and KIF5C. KIF5A is implicated in multiple neurodegenerative diseases (see OMIM:6028210), including spastic paraplegia 10 (FBhh0000037), neonatal myoclonus, and susceptibility to ALS; KIF5B is not known to be implicated in disease; KIF5C is implicated in cortical dysplasia (OMIM:615282). There are additional members of the kinesin heavy chain family in both species. Classical amorphic and loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\Khc.

Of the three human KIF5 genes, only KIF5B has been introduced into flies; neither of the disease-implicated genes has been introduced into flies.

Animals homozygous for amorphic alleles of Dmel\Khc typically die during embryogenesis; less severe mutations survive to later stages, allowing characterization of locomotor and neuroanatomy defects. Larvae exhibit progressive distal paralysis; weaker mutations result in a tail-flipping phenotype that is easily scored. Genetic and physical interaction(s) of the Dmel\Khc gene and protein product have been described; see below and in the gene report for Khc.

Variant(s) implicated in human disease tested (as analogous mutation in fly gene): N262S in the fly Khc gene (corresponds to N256S in the human KIF5A gene), this variant is implicated in spastic paraplegia 10 (see FBhh0000037).

[updated Jan. 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: neurodegenerative disease, KIF5-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information
External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one: 3 human to 1 Drosophila; additional less closely related genes in both species.

    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one: 3 human to 1 Drosophila; additional less closely related genes in both species.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      Kinesin heavy chain (Khc) encodes the force generating subunit of kinesin-1, a microtubule motor protein. It functions in the long-distance transport of cytoplasmic "cargoes" such as mRNAs, protein complexes, and organelles. [Date last reviewed: 2019-03-14]
      Gene Groups / Pathways
      Comments on ortholog(s)

      High-scoring ortholog of human KIF5A, KIF5B, and KIF5C (1 Drosophila to 3 human; additional less closely related genes in both species). Dmel\Khc shares 60-61% identity and 76-77% similarity with the human genes.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (23 groups)
        protein-protein
        Interacting group
        Assay
        References
        cosedimentation, molecular weight estimation by staining, fluorescent resonance energy transfer, fluorescence technology, inferred by author, enzymatic study, cross-linking study, x-ray crystallography
        anti tag coimmunoprecipitation, cross-linking study, Identification by mass spectrometry
        anti tag coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, western blot, two hybrid, anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, western blot, two hybrid
        coimmunoprecipitation, western blot, anti tag coimmunoprecipitation
        anti bait coimmunoprecipitation, anti tag western blot, anti tag coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation
        anti tag coimmunoprecipitation, anti tag western blot, western blot, coimmunoprecipitation, anti bait coimmunoprecipitation, Identification by mass spectrometry, experimental knowledge based
        pull down, western blot
        anti bait coimmunoprecipitation, western blot, pull down
        anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation
        pull down, western blot
        anti tag coimmunoprecipitation, anti tag western blot, western blot
        enzymatic study, autoradiography, anti bait coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, western blot, pull down
        experimental knowledge based
        pull down, anti tag western blot, anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry
        anti tag coimmunoprecipitation, cross-linking study, Identification by mass spectrometry
        pull down, western blot, anti tag coimmunoprecipitation, anti tag western blot, two hybrid
        Alleles Reported to Model Human Disease (Disease Ontology) (10 alleles)
        Models Based on Experimental Evidence ( 6 )
        Modifiers Based on Experimental Evidence ( 5 )
        Alleles Representing Disease-Implicated Variants
        Genetic Tools, Stocks and Reagents
        Sources of Stocks
        Contact lab of origin for a reagent not available from a public stock center.
        Bloomington Stock Center Disease Page
        Selected mammalian transgenes
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila transgenes
        Allele
        Transgene
        Publicly Available Stocks
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        loss of function allele
        ethyl methanesulfonate
        loss of function allele
        ethyl methanesulfonate
        loss of function allele
        ethyl methanesulfonate
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        loss of function allele
        ethyl methanesulfonate
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        ethyl methanesulfonate
        ethyl methanesulfonate
        ethyl methanesulfonate
        References (7)