This report describes a fly model of diseases associated with the human KIF1 kinesin-3 genes, primarily KIF1A, which functions as an anterograde motor protein that transports membranous organelles and synaptic vesicle precursors along axonal microtubules. KIF1A is implicated in three diseases, neuropathy, hereditary sensory, type IIC (HSN2C; MIM:614213; FBhh0000877), intellectual disability, autosomal dominant 9 (MRD9; MIM:614255; FBhh0000876), and spastic paraplegia 30 (SPG30; MIM:610357; FBhh0000878). The Drosophila gene unc-104 is the closest fly ortholog to KIF1A, as well as to human kinesins KIF1B and KIF1C; both KIF1B and KIF1C are also implicated in human disease, including a form of spastic ataxia (SPAX2, MIM:611302). Multiple genetic reagents have been generated for Dmel\unc-104, including loss-of-function mutations, RNAi-targeting constructs, alleles caused by insertional mutagenesis, and a targeted CRISPR knockout construct.
None of the human kinesin genes orthologous to Dmel\unc-104 has been introduced into flies.
Animals homozygous for the most severe mutations of unc-104 die during the embryonic stage. Less severe mutations survive to the third larval instar; these larvae exhibit locomotor, neuroanatomy and neurophysiology defects. Using larval neuromuscular junctions, a synapse maturation defect and synaptic transmission defects have been observed.
[updated Aug. 2021 by FlyBase; FBrf0222196]
KIF1A encodes a member of the kinesin family; it functions as an anterograde motor protein that transports membranous organelles and synaptic vesicle precursors along axonal microtubules. [Gene Cards, KIF1A; 2018.08.22]
The human genome includes 8 genes that encode members the family of kinesin-3 organelle transporters, which transport a variety of cargoes towards the plus end of microtubules (Siddiqui and Straube, 2017; pubmed:28918744).
Many to one: 3 human to 1 Drosophila; the human genes are KIF1A, KIF1B and KIF1C.
Many to one: 3 human to 1 Drosophila; the human genes are KIF1A, KIF1B and KIF1C.
Many to one: 3 human to 1 Drosophila; the human genes are KIF1A, KIF1B and KIF1C.
High-scoring ortholog of KIF1A and KIF1B; moderate-scoring ortholog of KIF1C (1 Drosophila to 3 human). Dmel\unc-104 shares 49-55% identity and 64-69% similarity with the human genes.
