title: The product of C9orf72, a gene strongly implicated in neurodegeneration, is structurally related to DENN Rab-GEFs.
abstract: BACKGROUND
  Fronto-temporal dementia (FTD) and amyotrophic lateral sclerosis (ALS, also called motor neuron disease, MND) are severe neurodegenerative diseases that show considerable overlap at the clinical and cellular level. The most common single mutation in families with FTD or ALS has recently been mapped to a non-coding repeat expansion in the uncharacterized gene C9ORF72. Although a plausible mechanism for disease is that aberrant C9ORF72 mRNA poisons splicing, it is important to determine the cellular function of C9ORF72, about which nothing is known.
  
  
  RESULTS
  Sensitive homology searches showed that C9ORF72 is a full-length distant homologue of proteins related to Differentially Expressed in Normal and Neoplasia (DENN), which is a GDP/GTP exchange factor (GEF) that activates Rab-GTPases. Our results suggest that C9ORF72 is likely to regulate membrane traffic in conjunction with Rab-GTPase switches, and we propose to name the gene and its product DENN-like 72 (DENNL72).
authors: Department of Cell Biology, UCL Institute of Ophthalmology, Bath St, London EC1V 9EL, UK. tim.levine@ucl.ac.uk
authors: Timothy P
authors: TP
authors: Levine
authors: Rachel D
authors: RD
authors: Daniels
authors: Alberto T
authors: AT
authors: Gatta
authors: Louise H
authors: LH
authors: Wong
authors: Matthew J
authors: MJ
authors: Hayes
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D000073885:C9orf72 Protein; D057180:Frontotemporal Dementia / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry* / Q000145:classification; D006801:Humans; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D020662:Guanine Nucleotide Exchange Factors; D011506:Proteins