GENE OVERVIEW OF KEY PUBLISHED STUDIES FOR ALS


GeneC9orf72
Other namesMGC23980; RP11-27J8.2; C9orf72
Gene namechromosome 9 open reading frame 72
Gene inheritanceFALS genes found in SALS
Discovery methodGWAS
Category 
Chromosome9p21.2
Genomic CoordinatesChr9:27546543-27573864 á( -)
BackgroundTo identify risk factors associated with ALS in a further genome-wide association study that combined data from the independent analysis with those from other countries
ResultFindings suggest that genetic variation at this locus on chromosome 9 causes sporadic ALS and familial ALS–frontotemporal dementia.
Total Mutations1
Total Affected76
FALSSALSMaleFemaleBulbarLimbNo dataMean age onsetN
40343638185635574

BIOINFORMATICS

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TOP META-ANALYSIS RESULT FROM ALSGENE

For more details on this and other meta-analysis results in this region please visit the ALSGene database

ANIMAL MODELS

                               

KEY PUBLICATIONS (70)

First_AuthorYearTitlePaper
Andersen2012Mutation in C9orf72 changes the boundaries of ALS and FTDFull_Paper
Ash2013Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALSFull_Paper
Beck2013Large C9orf72 hexanucleotide repeat expansions are seen in multiple neurodegenerative syndromes and are more frequent than expected in the UK populationFull_Paper
Bigio2011C9ORF72, the new gene on the block, causes C9FTD/ALS: new insights provided by neuropathologyFull_Paper
Bigio2012Motor neuron disease: the C9orf72 hexanucleotide repeat expansion in FTD and ALSFull_Paper
Boeve2012Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72Full_Paper
Boxer2010Clinical, neuroimaging and neuropathological features of a new chromosome 9p-linked FTD-ALS familyFull_Paper
Brettschneider2012Pattern of ubiquilin pathology in ALS and FTLD indicates presence of C9ORF72 hexanucleotide expansionFull_Paper
Byrne2012Cognitive and clinical characteristics of patients with amyotrophic lateral sclerosis carrying a C9orf72 repeat expansion: a population-based cohort studyFull_Paper
Calvo2012Amyotrophic lateral sclerosis/frontotemporal dementia with predominant manifestations of obsessive-compulsive disorder associated to GGGGCC expansion of the c9orf72 geneFull_Paper
Chester2012Rapidly progressive frontotemporal dementia and bulbar amyotrophic lateral sclerosis in Portuguese patients with C9orf72 mutationFull_Paper
Chester2012Rapidly progressive frontotemporal dementia and bulbar amyotrophic lateral sclerosis in Portuguese patients with C9orf72 mutationFull_Paper
Chio2012ALS/FTD phenotype in two Sardinian families carrying both C9ORF72 and TARDBP mutationsFull_Paper
Chio2012Clinical characteristics of patients with familial amyotrophic lateral sclerosis carrying the pathogenic GGGGCC hexanucleotide repeat expansion of C9ORF72Full_Paper
Conte2012Classification of familial amyotrophic lateral sclerosis by family history: effects on frequency of genes mutationFull_Paper
Coon2012Clinical and electrophysiologic variability in amyotrophic lateral sclerosis within a kindred harboring the C9ORF72 repeat expansionFull_Paper
Cooper-Knock2012Clinico-pathological features in amyotrophic lateral sclerosis with expansions in C9ORF72Full_Paper
DeJesus-Hernandez2011Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALSFull_Paper
Dobson-Stone2013Frontotemporal dementia-amyotrophic lateral sclerosis syndrome locus on chromosome 16p12Full_Paper
Dombroski2013C9orf72 hexanucleotide repeat expansion and Guam amyotrophic lateral sclerosis-Parkinsonism-dementia complexFull_Paper
G¾mez-Tortosa2013C9ORF72 hexanucleotide expansions of 20-22 repeats are associated with frontotemporal deteriorationFull_Paper
García-Redondo2012Analysis of the C9orf72 gene in patients with amyotrophic lateral sclerosis in Spain and different populations worldwideFull_Paper
GarcÝa-Redondo2012Analysis of the C9orf72 gene in patients with amyotrophic lateral sclerosis in Spain and different populations worldwideFull_Paper
Gijselinck2010Identification of 2 Loci at chromosomes 9 and 14 in a multiplex family with frontotemporal lobar degeneration and amyotrophic lateral sclerosisFull_Paper
Gijselinck2012A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification studyFull_Paper
Herdewyn2012Whole-genome sequencing reveals a coding non-pathogenic variant tagging a non-coding pathogenic hexanucleotide repeat expansion in C9orf72 as cause of amyotrophic lateral sclerosisFull_Paper
Hosler2000Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21-q22Full_Paper
Iida2011Replication analysis of SNPs on 9p21.2 and 19p13.3 with amyotrophic lateral sclerosis in East AsiansFull_Paper
Irwin2012Cognitive decline and reduced survival in C9orf72 expansion frontotemporal degeneration and amyotrophic lateral sclerosisFull_Paper
Ishiura2012C9ORF72 Repeat Expansion in Amyotrophic Lateral Sclerosis in the Kii Peninsula of JapanFull_Paper
Ismail2012Concurrence of multiple sclerosis and amyotrophic lateral sclerosis in patients with hexanucleotide repeat expansions of C9ORF72Full_Paper
Jang2012Analysis of the C9orf72 hexanucleotide repeat expansion in Korean patients with familial and sporadic amyotrophic lateral sclerosisFull_Paper
Jones2013Residual association at C9orf72 suggests an alternative amyotrophic lateral sclerosis-causing hexanucleotide repeatFull_Paper
King2012Mixed tau, TDP-43 and p62 pathology in FTLD associated with a C9ORF72 repeat expansion and p.Ala239Thr MAPT (tau) variantFull_Paper
Konno2012Japanese amyotrophic lateral sclerosis patients with GGGGCC hexanucleotide repeat expansion in C9ORF72Full_Paper
Koppers2012Screening for rare variants in the coding region of ALS-associated genes at 9p21Full_Paper
Laaksovirta2010Chromosome 9p21 in amyotrophic lateral sclerosis in Finland: a genome-wide association studyFull_Paper
Lattante2012Contribution of major amyotrophic lateral sclerosis genes to the etiology of sporadic diseaseFull_Paper
Le Ber2009Chromosome 9p-linked families with frontotemporal dementia associated with motor neuron diseaseFull_Paper
Luty2008Pedigree with frontotemporal lobar degeneration--motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9Full_Paper
Majounie2012Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional studyFull_Paper
Millecamps2012Phenotype difference between ALS patients with expanded repeats in C9ORF72 and patients with mutations in other ALS-related genesFull_Paper
Mok2012High frequency of the expanded C9ORF72 hexanucleotide repeat in familial and sporadic Greek ALS patientsFull_Paper
Mori2013The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALSFull_Paper
Morita2006A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementiaFull_Paper
Morris2012Recent advances in the genetics of the ALS-FTLD complexFull_Paper
Murray2011Clinical and neuropathologic heterogeneity of c9FTD/ALS associated with hexanucleotide repeat expansion in C9ORF72Full_Paper
Ogaki2012Analyses of the MAPT, PGRN, and C9orf72 mutations in Japanese patients with FTLD, PSP, and CBSFull_Paper
Ogaki2012Analysis of C9orf72 repeat expansion in 563 Japanese patients with amyotrophic lateral sclerosisFull_Paper
Orr2011FTD and ALS: genetic ties that bindFull_Paper
Ostojic2003No evidence of linkage to chromosome 9q21-22 in a Swedish family with frontotemporal dementia and amyotrophic lateral sclerosisFull_Paper
Pamplett2012Transmission of C9orf72 hexanucleotide repeat expansions in sporadic amyotrophic lateral sclerosis: an Australian trio studyFull_Paper
Pearson2010Familial frontotemporal dementia with amyotrophic lateral sclerosis and a shared haplotype on chromosome 9pFull_Paper
Rademakers2012C9orf72 repeat expansions in patients with ALS and FTDFull_Paper
Ratti2012C9ORF72 repeat expansion in a large Italian ALS cohort: evidence of a founder effectFull_Paper
Renton2011A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTDFull_Paper
Rutherford2012C9ORF72 hexanucleotide repeat expansions in patients with ALS from the Coriell Cell RepositoryFull_Paper
Sabatelli2012C9ORF72 hexanucleotide repeat expansions in the Italian sporadic ALS populationFull_Paper
Savica2012Characterization of a Family With c9FTD/ALS Associated With the GGGGCC Repeat Expansion in C9ORF72Characterization of a Family With c9FTD/ALSFull_Paper
Shatunov2010Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association studyFull_Paper
Simón-Sánchez2012The clinical and pathological phenotype of C9ORF72 hexanucleotide repeat expansionsFull_Paper
Smith2012The C9ORF72 expansion mutation is a common cause of ALS+/-FTD in Europe and has a single founderFull_Paper
Smith2012The C9ORF72 expansion mutation is a common cause of ALS+/-FTD in Europe and has a single founderFull_Paper
Stewart2012Clinical and pathological features of amyotrophic lateral sclerosis caused by mutation in the C9ORF72 gene on chromosome 9pFull_Paper
Valdmanis2007Three families with amyotrophic lateral sclerosis and frontotemporal dementia with evidence of linkage to chromosome 9pFull_Paper
van Es2009Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosisFull_Paper
van Langenhove2012The molecular basis of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrumFull_Paper
Vance2006Familial amyotrophic lateral sclerosis with frontotemporal dementia is linked to a locus on chromosome 9p13.2-21.3Full_Paper
Wood2011Amyotrophic lateral sclerosis: A hexanucleotide repeat expansion in C9ORF72 links amyotrophic lateral sclerosis and frontotemporal dementiaFull_Paper
Xu2013Expanded GGGGCC repeat RNA associated with amyotrophic lateral sclerosis and frontotemporal dementia causes neurodegenerationFull_Paper

GENETIC VARIATIONS

SNP (rs)BasepairpvalueAuthorYearTermPaper
 3849942275432819E-11Laaksovirta2010GRCh37Chromosome 9p21 in amyotrophic lateral sclerosis in Finland: a genome-wide association study
 3849942275432815E-11Shatunov2010GRCh37Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study
 2814707275363975E-11Shatunov2010GRCh37Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study
 2814707275363977E-09van Es2009GRCh37Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis
 3849942275432811E-08van Es2009GRCh37Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis