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-linke... See more...

Aliases for C9orf72 Gene

Aliases for C9orf72 Gene

  • C9orf72-SMCR8 Complex Subunit 2 3 5
  • Guanine Nucleotide Exchange C9orf72 3 4
  • Chromosome 9 Open Reading Frame 72 2
  • Protein C9orf72 3
  • DENNL72 3
  • FTDALS1 3
  • ALSFTD 3
  • DENND9 3
  • FTDALS 3

External Ids for C9orf72 Gene

Previous GeneCards Identifiers for C9orf72 Gene

  • GC09M027550
  • GC09M027538

Summaries for C9orf72 Gene

Entrez Gene Summary for C9orf72 Gene

  • 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]

GeneCards Summary for C9orf72 Gene

C9orf72 (C9orf72-SMCR8 Complex Subunit) is a Protein Coding gene. Diseases associated with C9orf72 include Frontotemporal Dementia And/Or Amyotrophic Lateral Sclerosis 1 and Huntington Disease-Like Syndrome Due To C9orf72 Expansions. Among its related pathways are Autophagy - animal and Mesodermal Commitment Pathway. Gene Ontology (GO) annotations related to this gene include Rab GTPase binding.

UniProtKB/Swiss-Prot Summary for C9orf72 Gene

  • Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:27193190, PubMed:27103069, PubMed:27617292, PubMed:28195531). In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation (PubMed:27103069). The C9orf72-SMCR8 complex also acts as a regulator of autophagy initiation by interacting with the ATG1/ULK1 kinase complex and modulating its protein kinase activity (PubMed:27617292). Positively regulates initiation of autophagy by regulating the RAB1A-dependent trafficking of the ATG1/ULK1 kinase complex to the phagophore which leads to autophagosome formation (PubMed:27334615). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (PubMed:27559131). Plays a role in endosomal trafficking (PubMed:24549040). May be involved in regulating the maturation of phagosomes to lysosomes (By similarity). Regulates actin dynamics in motor neurons by inhibiting the GTP-binding activity of ARF6, leading to ARF6 inactivation (PubMed:27723745). This reduces the activity of the LIMK1 and LIMK2 kinases which are responsible for phosphorylation and inactivation of cofilin, leading to cofilin activation (PubMed:27723745). Positively regulates axon extension and axon growth cone size in spinal motor neurons (PubMed:27723745). Plays a role within the hematopoietic system in restricting inflammation and the development of autoimmunity (By similarity).
  • [Isoform 1]: Regulates stress granule assembly in response to cellular stress.
  • [Isoform 2]: Does not play a role in regulation of stress granule assembly in response to cellular stress.

Additional gene information for C9orf72 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for C9orf72 Gene

Genomics for C9orf72 Gene

GeneHancer (GH) Regulatory Elements for C9orf72 Gene

Promoters and enhancers for C9orf72 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH09J027571 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 516.1 +0.9 865 4 ZBTB40 ZNF217 EP300 SIN3A MYC SP1 NCOR1 PHF8 JUND FOS C9orf72 5EW4_A-052 lnc-C9orf72-1 lnc-IFNK-10 MOB3B
GH09J027567 Promoter/Enhancer 0.5 EPDnew dbSUPER 500.4 +6.7 6669 0.1 C9orf72 5EW4_A-052 lnc-C9orf72-1 MOB3B
GH09J027527 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 17.1 +45.5 45465 4.8 EP300 CTCF ZIC2 POLR2A ZBTB26 REST RAD21 SKI TRIM22 EZH2 MOB3B ENSG00000285103 C9orf72 EQTN IFNK
GH09J027598 Enhancer 0.8 FANTOM5 ENCODE dbSUPER 30 -25.6 -25582 1 SPI1 REST FOS EBF1 C9orf72 HSALNG0070563 lnc-C9orf72-2
GH09J027455 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 17.8 +113.0 113048 10.4 ZBTB5 TAF9B NCOR1 FOXA2 NFIC ZNF263 FOS FOSL2 ZNF592 NR2F2 C9orf72 MOB3B ENSG00000237734 IFNK EQTN piR-32325-203 piR-36588-458 piR-50437-652
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around C9orf72 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for C9orf72

Top Transcription factor binding sites by QIAGEN in the C9orf72 gene promoter:
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • E2F-5

Genomic Locations for C9orf72 Gene

Genomic Locations for C9orf72 Gene
chr9:27,535,640-27,573,866
(GRCh38/hg38)
Size:
38,227 bases
Orientation:
Minus strand
chr9:27,546,544-27,573,864
(GRCh37/hg19)
Size:
27,321 bases
Orientation:
Minus strand

Genomic View for C9orf72 Gene

Genes around C9orf72 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
C9orf72 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for C9orf72 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for C9orf72 Gene

Proteins for C9orf72 Gene

  • Protein details for C9orf72 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96LT7-CI072_HUMAN
    Recommended name:
    Guanine nucleotide exchange C9orf72
    Protein Accession:
    Q96LT7
    Secondary Accessions:
    • A8K5W0
    • D3DRK6
    • G8I0B6
    • Q6NUS9

    Protein attributes for C9orf72 Gene

    Size:
    481 amino acids
    Molecular mass:
    54328 Da
    Quaternary structure:
    • Interacts with SMCR8; the interaction is direct (PubMed:27559131, PubMed:27617292). Component of the C9orf72-SMCR8 complex, at least composed of C9orf72, SMCR8 and WDR41 (PubMed:27193190, PubMed:27103069, PubMed:27559131, PubMed:27617292, PubMed:28195531). The C9orf72-SMCR8 complex associates with the ATG1/ULK1 kinase complex (PubMed:27617292, PubMed:28195531). Interacts with ATG1/ULK1 kinase complex members ULK1, ATG13 and RB1CC1 (PubMed:27334615). Interacts with HNRNPA1, HNRNPA2B1 and UBQLN2 (PubMed:24549040). Interacts with small Rab GTPase RAB1A; the interaction mediates recruitment of RAB1A to the ATG1/ULK1 kinase complex (PubMed:27334615). Also interacts with small Rab GTPase RAB7A (By similarity). Interacts with cofilin (PubMed:27723745). Interacts with GTP-binding proteins ARF1 and ARF6 (By similarity).
    Miscellaneous:
    • [Isoform 1]: Encoded by 2 transcripts differing in the 5' non-coding region.

    Alternative splice isoforms for C9orf72 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for C9orf72 Gene

Post-translational modifications for C9orf72 Gene

  • Ubiquitination at Lys388
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for C9orf72 Gene

Domains & Families for C9orf72 Gene

Gene Families for C9orf72 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for C9orf72 Gene

InterPro:
ProtoNet:
genes like me logo Genes that share domains with C9orf72: view

No data available for Suggested Antigen Peptide Sequences , Graphical View of Domain Structure and UniProtKB/Swiss-Prot for C9orf72 Gene

Function for C9orf72 Gene

Molecular function for C9orf72 Gene

UniProtKB/Swiss-Prot Function:
Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:27193190, PubMed:27103069, PubMed:27617292, PubMed:28195531). In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation (PubMed:27103069). The C9orf72-SMCR8 complex also acts as a regulator of autophagy initiation by interacting with the ATG1/ULK1 kinase complex and modulating its protein kinase activity (PubMed:27617292). Positively regulates initiation of autophagy by regulating the RAB1A-dependent trafficking of the ATG1/ULK1 kinase complex to the phagophore which leads to autophagosome formation (PubMed:27334615). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (PubMed:27559131). Plays a role in endosomal trafficking (PubMed:24549040). May be involved in regulating the maturation of phagosomes to lysosomes (By similarity). Regulates actin dynamics in motor neurons by inhibiting the GTP-binding activity of ARF6, leading to ARF6 inactivation (PubMed:27723745). This reduces the activity of the LIMK1 and LIMK2 kinases which are responsible for phosphorylation and inactivation of cofilin, leading to cofilin activation (PubMed:27723745). Positively regulates axon extension and axon growth cone size in spinal motor neurons (PubMed:27723745). Plays a role within the hematopoietic system in restricting inflammation and the development of autoimmunity (By similarity).
UniProtKB/Swiss-Prot Function:
[Isoform 1]: Regulates stress granule assembly in response to cellular stress.
UniProtKB/Swiss-Prot Function:
[Isoform 2]: Does not play a role in regulation of stress granule assembly in response to cellular stress.

Phenotypes From GWAS Catalog for C9orf72 Gene

Gene Ontology (GO) - Molecular Function for C9orf72 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005085 guanyl-nucleotide exchange factor activity IEA --
GO:0005515 protein binding IPI 21516116
GO:0017112 contributes_to Rab guanyl-nucleotide exchange factor activity IDA 27103069
GO:0017137 Rab GTPase binding IDA,IEA 24549040
genes like me logo Genes that share ontologies with C9orf72: view
genes like me logo Genes that share phenotypes with C9orf72: view

Human Phenotype Ontology for C9orf72 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for C9orf72 Gene

MGI Knock Outs for C9orf72:

Animal Model Products

CRISPR Products

miRNA for C9orf72 Gene

miRTarBase miRNAs that target C9orf72

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for C9orf72 Gene

Localization for C9orf72 Gene

Subcellular locations from UniProtKB/Swiss-Prot for C9orf72 Gene

Nucleus. Cytoplasm. Cytoplasm, P-body. Cytoplasm, Stress granule. Endosome. Lysosome. Cytoplasmic vesicle, autophagosome. Secreted. Cell projection, axon. Cell projection, growth cone. Perikaryon. Note=Detected in the cytoplasm of neurons from brain tissue (PubMed:21944778). Detected in the nucleus in fibroblasts (PubMed:21944779). During corticogenesis, transitions from being predominantly cytoplasmic to a more even nucleocytoplasmic distribution (By similarity). {ECO:0000250 UniProtKB:Q6DFW0, ECO:0000269 PubMed:21944778, ECO:0000269 PubMed:21944779, ECO:0000269 PubMed:27037575}.
[Isoform 1]: Perikaryon. Cell projection, dendrite. Note=Expressed diffusely throughout the cytoplasm and dendritic processes of cerebellar Purkinje cells. Also expressed diffusely throughout the cytoplasm of spinal motor neurons. {ECO:0000269 PubMed:26174152}.
[Isoform 2]: Nucleus membrane; Peripheral membrane protein. Nucleus. Note=Detected at the nuclear membrane of cerebellar Purkinje cells and spinal motor neurons. Also shows diffuse nuclear expression in spinal motor neurons. {ECO:0000269 PubMed:26174152}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for C9orf72 gene
Compartment Confidence
extracellular 5
nucleus 5
endosome 5
lysosome 5
cytoskeleton 3
mitochondrion 3
cytosol 3
plasma membrane 2
endoplasmic reticulum 2
peroxisome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for C9orf72 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000932 P-body IDA 27037575
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IDA,IEA 24549040
GO:0005634 nucleus IEA,IDA 24549040
GO:0005737 cytoplasm IEA,IDA 27037575
genes like me logo Genes that share ontologies with C9orf72: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for C9orf72 Gene

Pathways & Interactions for C9orf72 Gene

PathCards logo

SuperPathways for C9orf72 Gene

genes like me logo Genes that share pathways with C9orf72: view

Pathways by source for C9orf72 Gene

1 BioSystems pathway for C9orf72 Gene
1 KEGG pathway for C9orf72 Gene

Gene Ontology (GO) - Biological Process for C9orf72 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001933 negative regulation of protein phosphorylation IMP,IEA 27723745
GO:0006897 endocytosis IBA,IMP 24549040
GO:0006914 autophagy IBA,IMP 24549040
GO:0010506 regulation of autophagy IMP,IEA 27103069
GO:0016239 positive regulation of macroautophagy IGI,IMP 27103069
genes like me logo Genes that share ontologies with C9orf72: view

No data available for SIGNOR curated interactions for C9orf72 Gene

Drugs & Compounds for C9orf72 Gene

(1) Drugs for C9orf72 Gene - From: PharmGKB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Tumor necrosis factor alpha (TNF-alpha) inhibitors Pharma 0
genes like me logo Genes that share compounds with C9orf72: view

Transcripts for C9orf72 Gene

mRNA/cDNA for C9orf72 Gene

3 REFSEQ mRNAs :
15 NCBI additional mRNA sequence :
9 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for C9orf72 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6a · 6b · 6c ^ 7a · 7b ^ 8 ^ 9a · 9b ^ 10 ^ 11a · 11b ^ 12 ^ 13a · 13b
SP1: - -
SP2: -
SP3: - - -
SP4: -
SP5: -
SP6: - -
SP7:

Relevant External Links for C9orf72 Gene

GeneLoc Exon Structure for
C9orf72

Expression for C9orf72 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for C9orf72 Gene

mRNA differential expression in normal tissues according to GTEx for C9orf72 Gene

This gene is overexpressed in Whole Blood (x5.1).

Protein differential expression in normal tissues from HIPED for C9orf72 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (27.8), Testis (12.0), Ovary (10.4), Frontal cortex (9.4), and Placenta (9.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for C9orf72 Gene



Protein tissue co-expression partners for C9orf72 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for C9orf72

SOURCE GeneReport for Unigene cluster for C9orf72 Gene:

Hs.493639

mRNA Expression by UniProt/SwissProt for C9orf72 Gene:

Q96LT7-CI072_HUMAN
Tissue specificity: Both isoforms are widely expressed, including kidney, lung, liver, heart, testis and several brain regions, such as cerebellum. Also expressed in the frontal cortex and in lymphoblasts (at protein level).

Evidence on tissue expression from TISSUES for C9orf72 Gene

  • Nervous system(4.8)

Phenotype-based relationships between genes and organs from Gene ORGANizer for C9orf72 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • ear
  • epiglottis
  • face
  • head
  • jaw
  • larynx
  • mandible
  • maxilla
  • mouth
  • neck
  • nose
  • pharynx
  • skull
  • tongue
  • vocal cord
Thorax:
  • bronchus
  • clavicle
  • esophagus
  • heart
  • lung
  • scapula
  • trachea
Abdomen:
  • biliary tract
  • liver
  • stomach
Pelvis:
  • prostate
  • urinary bladder
Limb:
  • arm
  • digit
  • finger
  • foot
  • forearm
  • hand
  • humerus
  • lower limb
  • shin
  • shoulder
  • thigh
  • toe
  • upper limb
General:
  • blood vessel
  • peripheral nerve
  • peripheral nervous system
  • spinal cord
genes like me logo Genes that share expression patterns with C9orf72: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery for C9orf72 Gene

Orthologs for C9orf72 Gene

This gene was present in the common ancestor of animals.

Orthologs for C9orf72 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia C9orf72 31
  • 100 (a)
OneToOne
C9H9orf72 30
  • 99.58 (n)
cow
(Bos Taurus)
Mammalia C9orf72 31
  • 99 (a)
OneToOne
C8H9orf72 30
  • 91.89 (n)
dog
(Canis familiaris)
Mammalia C9orf72 31
  • 99 (a)
OneToOne
C11H9orf72 30
  • 93.76 (n)
oppossum
(Monodelphis domestica)
Mammalia C9orf72 31
  • 97 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia C9orf72 31
  • 95 (a)
OneToOne
mouse
(Mus musculus)
Mammalia 3110043O21Rik 31 30
  • 90.44 (n)
OneToOne
C9orf72 17
rat
(Rattus norvegicus)
Mammalia RGD1359108 30
  • 89.4 (n)
chicken
(Gallus gallus)
Aves C9orf72 31
  • 94 (a)
OneToOne
C9ORF72 30
  • 83.3 (n)
lizard
(Anolis carolinensis)
Reptilia C9orf72 31
  • 93 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii C13H9orf72 31
  • 76 (a)
OneToOne
zgc:100846 30
  • 68.55 (n)
worm
(Caenorhabditis elegans)
Secernentea alfa-1 31
  • 15 (a)
OneToOne
Species where no ortholog for C9orf72 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for C9orf72 Gene

ENSEMBL:
Gene Tree for C9orf72 (if available)
TreeFam:
Gene Tree for C9orf72 (if available)

Paralogs for C9orf72 Gene

No data available for Paralogs for C9orf72 Gene

Variants for C9orf72 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for C9orf72 Gene

SNP ID Clinical significance and condition Chr 09 pos Variation AA Info Type
rs10122902 Benign: Amyotrophic lateral sclerosis and/or frontotemporal dementia 1; Amyotrophic Lateral Sclerosis/Frontotemporal Dementia 27,556,782(-) G/A SYNONYMOUS_VARIANT
rs10757668 Likely Benign: Amyotrophic Lateral Sclerosis/Frontotemporal Dementia 27,567,147(-) C/T FIVE_PRIME_UTR_VARIANT
rs11292923 Uncertain Significance: Amyotrophic Lateral Sclerosis/Frontotemporal Dementia. Uncertain Significance: Amyotrophic Lateral Sclerosis/Frontotemporal Dementia. Uncertain Significance: Amyotrophic Lateral Sclerosis/Frontotemporal Dementia. Uncertain Significance: Amyotrophic Lateral Sclerosis/Frontotemporal Dementia. Uncertain Significance: Amyotrophic Lateral Sclerosis/Frontotemporal Dementia. Benign: Amyotrophic Lateral Sclerosis/Frontotemporal Dementia 27,548,435(-) G/GAG/GAAAG/GAAAAG/GAAAAAGA/GGAAA/G INTRON_VARIANT
rs13691 Benign: Amyotrophic Lateral Sclerosis/Frontotemporal Dementia 27,546,892(-) G/A THREE_PRIME_UTR_VARIANT
rs139352974 Benign/Likely Benign: Amyotrophic Lateral Sclerosis/Frontotemporal Dementia; not provided 27,550,641(-) A/G INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for C9orf72 Gene

Structural Variations from Database of Genomic Variants (DGV) for C9orf72 Gene

Variant ID Type Subtype PubMed ID
nsv1015259 CNV gain 25217958
nsv831532 CNV gain 17160897

Variation tolerance for C9orf72 Gene

Residual Variation Intolerance Score: 17.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.02; 60.36% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for C9orf72 Gene

Human Gene Mutation Database (HGMD)
C9orf72
SNPedia medical, phenotypic, and genealogical associations of SNPs for
C9orf72

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for C9orf72 Gene

Disorders for C9orf72 Gene

MalaCards: The human disease database

(74) MalaCards diseases for C9orf72 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
frontotemporal dementia and/or amyotrophic lateral sclerosis 1
  • ftdals1
huntington disease-like syndrome due to c9orf72 expansions
  • c9orf72-related huntington disease phenocopy
amyotrophic lateral sclerosis 1
  • als1
frontotemporal dementia
  • multiple system tauopathy with presenile dementia
dementia
  • dementias
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

CI072_HUMAN
  • Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 (FTDALS1) [MIM:105550]: An autosomal dominant neurodegenerative disorder characterized by adult onset of frontotemporal dementia and/or amyotrophic lateral sclerosis in an affected individual. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. {ECO:0000269 PubMed:21944778, ECO:0000269 PubMed:21944779, ECO:0000269 PubMed:22936364}. Note=The disease is caused by mutations affecting the gene represented in this entry. In the first intron of the gene, the expansion of a GGGGCC hexanucleotide that can vary from 10 to thousands of repeats, represents the most common genetic cause of both familial and sporadic FTDALS. The hexanucleotide repeat expansion (HRE) is structurally polymorphic and during transcription, is responsible for the formation of RNA and DNA G-quadruplexes resulting in the production of aborted transcripts at the expense of functional transcripts. The accumulation of those aborted transcripts may cause nucleolar stress and indirectly cell death (PubMed:24598541). The expanded GGGGCC repeats are bidirectionally transcribed into repetitive RNA, which forms sense and antisense RNA foci. Remarkably, despite being within a non-coding region, these repetitive RNAs can be translated in every reading frame to form five different dipeptide repeat proteins (DPRs) -- poly-GA, poly-GP, poly-GR, poly-PA and poly-PR -- via a non-canonical mechanism known as repeat-associated non-ATG (RAN) translation. These dipeptide repeat proteins (DPRs) co-aggregate in the characteristic SQSTM1-positive TARDBP negative inclusions found in FTLD/ALS patients with C9orf72 repeat expansion (PubMed:24132570). {ECO:0000269 PubMed:24132570, ECO:0000269 PubMed:24598541}.

Additional Disease Information for C9orf72

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with C9orf72: view

No data available for Genatlas for C9orf72 Gene

Publications for C9orf72 Gene

  1. C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking. (PMID: 24549040) Farg MA … Atkin JD (Human molecular genetics 2014) 2 3 4 54
  2. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. (PMID: 21944778) DeJesus-Hernandez M … Rademakers R (Neuron 2011) 2 3 4 54
  3. C9orf72, a protein associated with amyotrophic lateral sclerosis (ALS) is a guanine nucleotide exchange factor. (PMID: 30356970) Iyer S … Acharya KR (PeerJ 2018) 2 3 54
  4. Multiplex image-based autophagy RNAi screening identifies SMCR8 as ULK1 kinase activity and gene expression regulator. (PMID: 28195531) Jung J … Behrends C (eLife 2017) 3 4 54
  5. C9ORF72 Regulates Stress Granule Formation and Its Deficiency Impairs Stress Granule Assembly, Hypersensitizing Cells to Stress. (PMID: 27037575) Maharjan N … Saxena S (Molecular neurobiology 2017) 3 4 54

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Sources for C9orf72 Gene