ALS2

The protein encoded by this gene contains an ATS1/RCC1-like domain, a RhoGEF domain, and a vacuolar protein sorting 9 (VPS9) domain, all of which are guanine-nucleotide exchange factors that activate members of the Ras superfamily of GTPases. The protein functions as a guanine nucleotide exchange factor for the small GTPase RAB5. The protein localizes with RAB5 on early endosomal compartments, and functions as a modulator for endosomal dynamics. Mutations in this gene result in several forms of juvenile lateral sclerosis and infantile-onset ascending spastic paralysis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq]

amyotrophic lateral sclerosis 2 (juvenile)

May act as a GTPase regulator. Controls survival and growth of spinal motoneurons (By similarity).

Endosome organization Source: MGI
Lysosomal transport Source: MGI
Neuron projection morphogenesis Source: UniProtKB
Positive regulation of GTPase activity Source: UniProtKB
Positive regulation of protein kinase activity Source: UniProtKB
Positive regulation of Rac protein signal transduction Source: UniProtKB
Protein homooligomerization Source: MGI
Regulation of endosome size Source: UniProtKB

Centrosome; Cytosol; Early endosome; Nucleus; Dendrite; Growth cone; Lamellipodium; Protein-containing complex; Ruffle; Vesicle

Amyotrophic lateral sclerosis 2 (ALS2): A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.
Juvenile primary lateral sclerosis (JPLS): A neurodegenerative disorder which is closely related to but clinically distinct from amyotrophic lateral sclerosis. It is a progressive paralytic disorder which results from dysfunction of the upper motor neurons while the lower neurons are unaffected.
Infantile-onset ascending spastic paralysis (IAHSP): Characterized by progressive spasticity and weakness of limbs.