This report describes amyotrophic lateral sclerosis, susceptibility to, 24, a subtype of amyotrophic lateral sclerosis. The human gene implicated is NEK1, which encodes NIMA related kinase 1, a serine/threonine kinase involved in cell cycle regulation. NEK1 is also associated with short-rib thoracic dysplasia 6 with or without polydactyly (MIM:263520), and with orofaciodigital syndrome II (MIM:252100). There are two low-scoring fly orthologs, Dmel\niki, for which multiple genetic reagents, including classical alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated, and Dmel\Nek2.
Human NEK1 has not been introduced into flies.
Motor neuron-specific RNAi knockdown of Dmel\niki resulted in a significant reduction climbing velocity in young and in 20 day old flies, as well as an age-dependent reduction in the percentage of flies able to climb 4 centimeters within 20 seconds, and a reduction in lifespan.
[updated June 2024 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, 24; ALS24](https://omim.org/entry/617892)
[NIMA-RELATED KINASE 1; NEK1](https://omim.org/entry/604588)
Amyotrophic lateral sclerosis-24 (ALS24) is a fatal neurodegenerative disease characterized by adult-onset loss of motor neurons (Brenner et al., 2016, pubmed:26945885). [from MIM:617892 2024.07.03]
Susceptibility to amyotrophic lateral sclerosis-24 (ALS24) is conferred by heterozygous mutation in the NEK1 gene on chromosome 4q33. [from MIM:617892 2024.07.03]
NEK1 encodes a serine/threonine kinase involved in cell cycle regulation. The encoded protein is found in a centrosomal complex with FEZ1, a neuronal protein that plays a role in axonal development. [provided by RefSeq, Dec 2010]
NIMA-related kinases (NEKs), such as NEK1, form an evolutionarily conserved family of serine/threonine kinases thought to function in cell cycle control and cilia regulation. NEK1 has proposed functions in DNA double-strand repair, neuronal development, and coordination of cell cycle-associated ciliogenesis (summary by Thiel et al., 2011, pubmed: 21211617). [from MIM:604588 2024.07.03]
High-scoring ortholog of human NEK8, moderate-scoring ortholog of human NEK9, low-scoring ortholog of human NKE1, NEK3, NEK4, NEK5, NEK11, NEK2 (2 Drosophila to many human).
Moderate-scoring ortholog of human NEK2, low-scoring ortholog of NEK1, NEK3, NEK5, NEK6, NEK7, NEK8, NEK11 (2 Drosophila to many human).
