U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

C9orf72 C9orf72-SMCR8 complex subunit [ Homo sapiens (human) ]

Gene ID: 203228, updated on 2-Nov-2024

Summary

Go to the top of the page Help
Official Symbol
C9orf72provided by HGNC
Official Full Name
C9orf72-SMCR8 complex subunitprovided by HGNC
Primary source
HGNC:HGNC:28337
See related
Ensembl:ENSG00000147894 MIM:614260; AllianceGenome:HGNC:28337
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ALSFTD; DENND9; FTDALS; DENNL72; FTDALS1
Summary
The protein encoded by this gene plays an important role in the regulation of endosomal trafficking, and has been shown to interact with Rab proteins that are involved in autophagy and endocytic transport. Expansion of a GGGGCC repeat from 2-22 copies to 700-1600 copies in the intronic sequence between alternate 5' exons in transcripts from this gene is associated with 9p-linked ALS (amyotrophic lateral sclerosis) and FTD (frontotemporal dementia) (PMID: 21944778, 21944779). Studies suggest that hexanucleotide expansions could result in the selective stabilization of repeat-containing pre-mRNA, and the accumulation of insoluble dipeptide repeat protein aggregates that could be pathogenic in FTD-ALS patients (PMID: 23393093). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2016]
Expression
Ubiquitous expression in appendix (RPKM 9.7), testis (RPKM 9.3) and 25 other tissues See more
Orthologs
mouse all
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
See C9orf72 in Genome Data Viewer
Location:
9p21.2
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (27546546..27573866, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (27557112..27584475, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (27546544..27573864, complement)

Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene MOB kinase activator 3B Neighboring gene dapper homolog 3-like Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19820 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19821 Neighboring gene Sharpr-MPRA regulatory region 13504 Neighboring gene interferon kappa Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28254 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19822 Neighboring gene chromosome 9 open reading frame 72 repeat instability region Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:27573561-27574088 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:27610369-27610870 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:27610871-27611370 Neighboring gene CTAGE family member 12, pseudogene Neighboring gene uncharacterized LOC107987058

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the pageHelp

Related articles in PubMed

  1. C9ORF72 protein function and immune dysregulation in amyotrophic lateral sclerosis. Lai JD, et al. Neurosci Lett, 2019 Nov 20. PMID 31568865
  2. Increased prevalence of granulovacuolar degeneration in C9orf72 mutation. Riku Y, et al. Acta Neuropathol, 2019 Nov. PMID 31144027
  3. Presymptomatic spinal cord pathology in c9orf72 mutation carriers: A longitudinal neuroimaging study. Querin G, et al. Ann Neurol, 2019 Aug. PMID 31177556
  4. C9orf72 intermediate expansions of 24-30 repeats are associated with ALS. Iacoangeli A, et al. Acta Neuropathol Commun, 2019 Jul 17. PMID 31315673, Free PMC Article
  5. C9orf72 intermediate repeats are associated with corticobasal degeneration, increased C9orf72 expression and disruption of autophagy. Cali CP, et al. Acta Neuropathol, 2019 Nov. PMID 31327044, Free PMC Article

See all (624) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Molecular pathology, developmental changes and synaptic dysfunction in (pre-) symptomatic human C9ORF72-ALS/FTD cerebral organoids.
    Title: Molecular pathology, developmental changes and synaptic dysfunction in (pre-) symptomatic human C9ORF72-ALS/FTD cerebral organoids.
  2. C9orf72 gene repeat expansion phenotype profile of motor neurone disease in Portugal.
    Title: C9orf72 gene repeat expansion phenotype profile of motor neurone disease in Portugal.
  3. Toxic gain-of-function mechanisms in C9orf72 ALS-FTD neurons drive autophagy and lysosome dysfunction.
    Title: Toxic gain-of-function mechanisms in C9orf72 ALS-FTD neurons drive autophagy and lysosome dysfunction.
  4. Unveiling New Genetic Variants Associated with Age at Onset in Alzheimer's Disease and Frontotemporal Lobar Degeneration Due to C9orf72 Repeat Expansions.
    Title: Unveiling New Genetic Variants Associated with Age at Onset in Alzheimer's Disease and Frontotemporal Lobar Degeneration Due to C9orf72 Repeat Expansions.
  5. Cellular and axonal transport phenotypes due to the C9ORF72 HRE in iPSC motor and sensory neurons.
    Title: Cellular and axonal transport phenotypes due to the C9ORF72 HRE in iPSC motor and sensory neurons.
  6. Antisense RNA C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms a triplex-like structure and binds small synthetic ligand.
    Title: Antisense RNA C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms a triplex-like structure and binds small synthetic ligand.
  7. Somatic and intergenerational G4C2 hexanucleotide repeat instability in a human C9orf72 knock-in mouse model.
    Title: Somatic and intergenerational G4C2 hexanucleotide repeat instability in a human C9orf72 knock-in mouse model.
  8. Distinct neural signatures of pulvinar in C9orf72 amyotrophic lateral sclerosis mutation carriers and noncarriers.
    Title: Distinct neural signatures of pulvinar in C9orf72 amyotrophic lateral sclerosis mutation carriers and noncarriers.
  9. Abundant transcriptomic alterations in the human cerebellum of patients with a C9orf72 repeat expansion.
    Title: Abundant transcriptomic alterations in the human cerebellum of patients with a C9orf72 repeat expansion.
  10. Neuromuscular organoids model spinal neuromuscular pathologies in C9orf72 amyotrophic lateral sclerosis.
    Title: Neuromuscular organoids model spinal neuromuscular pathologies in C9orf72 amyotrophic lateral sclerosis.
Submit: New GeneRIF Correction See all GeneRIFs (569)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1.
EBI GWAS Catalog
Chromosome 9p21 in amyotrophic lateral sclerosis in Finland: a genome-wide association study.
EBI GWAS Catalog
Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study.
EBI GWAS Catalog
Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis.
EBI GWAS Catalog
Genome-wide association study identifies genetic determinants of urine PCA3 levels in men.
EBI GWAS Catalog

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Homology

Clone Names

  • MGC23980

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables GTPase activator activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
contributes_to guanyl-nucleotide exchange factor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables small GTPase binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in autophagy IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in autophagy IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in axon extension IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in endocytosis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in endocytosis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in late endosome to lysosome transport ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of exocytosis NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in negative regulation of immune response NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in negative regulation of protein phosphorylation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of macroautophagy IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in positive regulation of macroautophagy IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of TORC1 signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of actin filament organization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of autophagosome assembly IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of autophagy IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of autophagy NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in regulation of protein localization IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of synaptic vesicle cycle IEA
Inferred from Electronic Annotation
more info
  
involved_in stress granule assembly IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
part_of Atg1/ULK1 kinase complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in Flemming body IDA
Inferred from Direct Assay
more info
  
located_in P-body IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in autophagosome IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in autophagosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in axonal growth cone IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm NAS
Non-traceable Author Statement
more info
 PubMed 
located_in cytoplasmic stress granule IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in dendrite IDA
Inferred from Direct Assay
more info
 PubMed 
located_in dendrite IEA
Inferred from Electronic Annotation
more info
  
is_active_in endosome IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in extracellular space IDA
Inferred from Direct Assay
more info
 PubMed 
located_in glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
  
part_of guanyl-nucleotide exchange factor complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of guanyl-nucleotide exchange factor complex IPI
Inferred from Physical Interaction
more info
 PubMed 
located_in hippocampal mossy fiber to CA3 synapse IEA
Inferred from Electronic Annotation
more info
  
located_in intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
  
located_in lysosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in main axon IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nuclear membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nuclear membrane IEA
Inferred from Electronic Annotation
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in perikaryon IDA
Inferred from Direct Assay
more info
 PubMed 
located_in perikaryon IEA
Inferred from Electronic Annotation
more info
  
located_in postsynapse IEA
Inferred from Electronic Annotation
more info
  
is_active_in presynaptic cytosol IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

Go to the top of the page Help
Preferred Names
guanine nucleotide exchange factor C9orf72
Names
guanine nucleotide exchange C9orf72
protein C9orf72

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_031977.2 RefSeqGene

    Range
    5386..32321
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_658

mRNA and Protein(s)

  1. NM_001256054.3 → NP_001242983.1  guanine nucleotide exchange factor C9orf72 isoform a

    See identical proteins and their annotated locations for NP_001242983.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) represents the longest transcript and encodes the longer isoform (a). Hexanucleotide expansions that can occur in a repeat region between the first and second exon of this variant have been associated with frontotemporal dementia and amyotrophic lateral sclerosis (FTD-ALS;PMID: 21944778, PMID: 21944779 ). Variants 2 and 3 encode the same protein.
    Source sequence(s)
    AL832229, BQ068108, JN681271
    Consensus CDS
    CCDS6522.1
    UniProtKB/Swiss-Prot
    A8K5W0, D3DRK6, G8I0B6, Q6NUS9, Q96LT7
    UniProtKB/TrEMBL
    A0A2R8Y5K2
    Related
    ENSP00000482753.1, ENST00000619707.5
    Conserved Domains (1) summary
    pfam15019
    Location:61 → 324
    C9orf72-like; C9orf72-like protein family

  2. NM_018325.5 → NP_060795.1  guanine nucleotide exchange factor C9orf72 isoform a

    See identical proteins and their annotated locations for NP_060795.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 3. Both variants 2 and 3 encode the same protein.
    Source sequence(s)
    AK291425, AL832229, BC020851, BC039112, BC068445, BQ777139
    Consensus CDS
    CCDS6522.1
    UniProtKB/Swiss-Prot
    A8K5W0, D3DRK6, G8I0B6, Q6NUS9, Q96LT7
    UniProtKB/TrEMBL
    A0A2R8Y5K2
    Related
    ENSP00000369339.3, ENST00000380003.8
    Conserved Domains (1) summary
    pfam15019
    Location:61 → 324
    C9orf72-like; C9orf72-like protein family

  3. NM_145005.7 → NP_659442.2  guanine nucleotide exchange factor C9orf72 isoform b

    See identical proteins and their annotated locations for NP_659442.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) lacks multiple exons in the central and 3' coding regions, and its 3' terminal exon extends beyond a splice site that is used in variant 3 . This results in a novel 3' UTR, compared to variant 3. It encodes isoform b which is significantly shorter, and its C-terminal amino acid is distinct, compared to isoform a.
    Source sequence(s)
    AI141996, AK057806, BC020851, BQ068108, DA802421
    Consensus CDS
    CCDS6523.1
    UniProtKB/Swiss-Prot
    Q96LT7
    Related
    ENSP00000369333.3, ENST00000379997.7
    Conserved Domains (1) summary
    pfam15019
    Location:61 → 222
    C9orf72-like; C9orf72-like protein family

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000009.12 Reference GRCh38.p14 Primary Assembly

    Range
    27546546..27573866 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060933.1 Alternate T2T-CHM13v2.0

    Range
    27557112..27584475 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q96LT7.2 GenPept UniProtKB/Swiss-Prot:Q96LT7

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Other Literature Sources
Chemical Information
Medical
Molecular Biology Databases
Research Materials
Tools