This report describes amyotrophic lateral sclerosis, susceptibilty to, 25, which is a subtype of amyotrophic lateral sclerosis. The human gene implicated in this disease is KIF5A, a kinesin heavy chain gene. KIF5A is one of three human genes orthologous to the Drosophila gene Khc. Classical amorphic and loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis are available for Dmel\Khc.
UAS constructs of the human Hsap\KIF5A gene, both wild-type and a variant implicated in ALS25, have been introduced into flies. See the 'Disease-Implicated Variants' table below.
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.
[updated Nov. 2022 by FlyBase; FBrf0222196]
Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. ALS usually begins with asymmetric involvement of the muscles in middle adult life. Approximately 10% of ALS cases are familial (Siddique and Deng, 1996, pubmed:8875253). ALS is sometimes referred to as 'Lou Gehrig disease' after the famous American baseball player who was diagnosed with the disorder. [from MIM:105400, 2015.02.11]
[AMYOTROPHIC LATERAL SCLEROSIS, SUSCEPTIBILITY TO, 25; ALS25](https://omim.org/entry/617921)
[KINESIN FAMILY MEMBER 5A; KIF5A](https://omim.org/entry/602821)
Amyotrophic lateral sclerosis is a neurodegenerative disorder clinically characterized by rapidly progressive muscle weakness and death due to respiratory failure (Nicolas et al., 2018; pubmed:29566793). [from MIM:617921; 2022.09.02]
Amyotrophic lateral sclerosis, susceptibilty to, 25 is conferred by heterozygous mutation in the KIF5A gene on chromosome 12q13. [from MIM:617921; 2022.09.01]
KIF5A encodes a kinesin heavy chain; kinesins are microtubule-based motor proteins involved in the transport of organelles. In neurons, kinesins are essential for intracellular movement of membranous organelles and other macromolecular cargo from the neuronal cell body to the distal tip of the axon (Niclas et al., 1994; pubmed:7514426; Kanai et al. 2004; pubmed:15312650). [from MIM:602821; 2022.09.02]
Many to one: many human to 1 Drosophila; additional human orthologous genes are KIF5B and KIF5C.
Ortholog of human genes KIF5A, KIF5B and KIF5C (1 Drosophila to many human). Dmel\Khc shares 60% identity and 76% similarity with human KIF5A; 61% identity and 77% similarity with human KIF5B; and 61% identity and 77% similarity with human KIF5C.
