ALS2

Chr 2AR

alsin Rho guanine nucleotide exchange factor ALS2

Also known as: ALS2CR6, ALSJ, IAHSP, PLSJ

NCBI Gene: 57679 ENSG00000003393 UniProt: Q96Q42 OMIM: 606352

The protein functions as a guanine nucleotide exchange factor for the small GTPase RAB5, localizing to early endosomal compartments where it modulates endosomal dynamics. Mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis, juvenile primary lateral sclerosis, and infantile-onset ascending spastic paralysis. The pathogenic mechanism involves disruption of endosomal trafficking through impaired RAB5 activation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM

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, Oct 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Amyotrophic lateral sclerosis 2, juvenileMIM #205100

Primary lateral sclerosis, juvenileMIM #606353

Spastic paralysis, infantile onset ascendingMIM #607225

Amyotrophic lateral sclerosis 2, juvenileMIM #205100

UniProtJuvenile primary lateral sclerosis

UniProtInfantile-onset ascending spastic paralysis

Clinical highlights

Gene-disease validity (ClinGen)

ALS2-related motor neuron disease · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.52

LOEUF

LOF

Mechanism· G2P

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GeneReview available — ALS2