Home Page
References OMIM Gene GeneReviews HGMD HGNC
GENATLAS PHENOTYPE
last update : 27-02-2015
Symbol ALS6
Location 16p11.2
Name amyotrophic lateral sclerosis 6
Other name(s) Lou Gehrigh's disease
Corresponding gene FUS
Main clinical features
  • degenerative motor neuron disorder characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis
    • Genetic determination autosomal recessive
    autosomal dominant
    Prevalence ALS ( all forms) is familial in 10 percent of cases
    Related entries ALS10
    Function/system disorder neurology
    Type disease
    Gene product
    Name an RNA- and DNA-binding protein, functioning in diverse processes, and normally located in the nucleus
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    missense   abnormal protein/loss of function mostly substitution of arginine residues on the C terminus of FUS with cytoplasmic inclusions in motor neurons of patients
    Remark(s)
  • neuronal cytoplasmic protein aggregation and defective RNA metabolism appear to be common pathogenic mechanisms involved in ALS
  • C-terminal ALS-associated FUS mutations leading to pathological FUS inclusions mostly observed in the cytosol, and inclusion-bearing cells often show a reduction of nuclear staining, and cause a toxic gain-of-function because of excessive accumulation in the cytoplasm (PMID: 20606625))
  • R495X FUS, which abrogates a putative nuclear localization signal at the C-terminus of FUS, caused a striking cytoplasmic accumulation of the protein to a greater extent than that observed for recessive (H517Q) and dominant (R521G) missense mutants (PMID: 20699327))
  • mutations in the PY-NLS disrupted nuclear import of FUS, causing its mislocalization and aggregation in the cytoplasm, as evidenced by cytoplasmic FUS inclusions in motor neurons of ALS6 patients (PMID: 22778397))
  • mutant FUS induces fragmentation of the Golgi apparatus which is enhanced by ATXN2 polyQ31 (PMID: 23072909))
    • Genotype/Phenotype correlations phenotypic variability suggest possible modifying genetic factors