The product of C9orf72, a gene strongly implicated in neurodegeneration, is structurally related to DENN Rab-GEFs

Bioinformatics. 2013 Feb 15;29(4):499-503. doi: 10.1093/bioinformatics/bts725. Epub 2013 Jan 16.


Motivation: 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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • C9orf72 Protein
  • Frontotemporal Dementia / genetics
  • Guanine Nucleotide Exchange Factors / chemistry*
  • Guanine Nucleotide Exchange Factors / classification
  • Humans
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Proteins / classification
  • Proteins / genetics
  • Sequence Homology, Amino Acid


  • C9orf72 Protein
  • C9orf72 protein, human
  • Guanine Nucleotide Exchange Factors
  • Proteins