title: Bioinformatics Data Mining Approach Suggests Coexpression of AGTPBP1 with an ALS-linked Gene C9orf72.
abstract: BACKGROUND
  Expanded GGGGCC hexanucleotide repeats located in the noncoding region of the chromosome 9 open reading frame 72 (C9orf72) gene represent the most common genetic abnormality for familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Formation of nuclear RNA foci, accumulation of repeat-associated non-ATG-translated dipeptide-repeat proteins, and haploinsufficiency of C9orf72 are proposed for pathological mechanisms of C9ALS/FTD. However, at present, the physiological function of C9orf72 remains largely unknown.
  
  
  METHODS
  By searching on a bioinformatics database named COXPRESdb composed of the comprehensive gene coexpression data, we studied potential C9orf72 interactors.
  
  
  RESULTS
  We identified the ATP/GTP binding protein 1 (AGTPBP1) gene alternatively named NNA1 encoding a cytosolic carboxypeptidase whose mutation is causative of the degeneration of Purkinje cells and motor neurons as the most significant gene coexpressed with C9orf72. We verified coexpression and interaction of AGTPBP1 and C9orf72 in transfected cells by immunoprecipitation and in neurons of the human brain by double-labeling immunohistochemistry. Furthermore, we found a positive correlation between AGTPBP1 and C9orf72 mRNA expression levels in the set of 21 human brains examined.
  
  
  CONCLUSIONS
  These results suggest that AGTPBP1 serves as a C9orf72 interacting partner that plays a role in the regulation of neuronal function in a coordinated manner within the central nervous system.
authors.affiliation: Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan.
authors.forename: Shouta
authors.initials: S
authors.lastname: Kitano
authors.affiliation: Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kino
authors.affiliation: Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Takitani
authors.affiliation: Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Miyoshi
authors.affiliation: Department of Pathology and Laboratory Medicine, Kohnodai Hospital, NCGM, Ichikawa, Chiba, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Laboratory Medicine, National Center Hospital, NCNP, Kodaira, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Psychiatry, Komoro Kogen Hospital, Komoro, Nagano, Japan.
authors.forename: Kunimasa
authors.initials: K
authors.lastname: Arima
authors.affiliation: Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Satoh
keywords: AGTPBP1; C9orf72; CCP1; COXPRESdb; NNA1; amyotrophic lateral sclerosis; bioinformatics; coexpression; frontotemporal dementia