======= C9orf72 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: C9orf72
  * **<color #00a2e8>Official Name</color>**: C9orf72-SMCR8 complex subunit
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=203228|203228]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q96LT7|Q96LT7]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=C9orf72&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20C9orf72|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/614260|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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). {ECO:0000250|UniProtKB:Q6DFW0, ECO:0000269|PubMed:24549040, ECO:0000269|PubMed:27103069, ECO:0000269|PubMed:27193190, ECO:0000269|PubMed:27334615, ECO:0000269|PubMed:27559131, ECO:0000269|PubMed:27617292, ECO:0000269|PubMed:27723745, ECO:0000269|PubMed:28195531}. Isoform 2: Does not play a role in regulation of stress granule assembly in response to cellular stress. {ECO:0000269|PubMed:27037575}.

<button type='default' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
No Pfam Domain information is available for this gene.
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|negative regulation of GTP binding|
|late endosome to lysosome transport|
|main axon|
|Atg1/ULK1 kinase complex|
|guanyl-nucleotide exchange factor complex|
|regulation of GTP binding|
|stress granule assembly|
|axonal growth cone|
|axon extension|
|regulation of autophagosome assembly|
|Rab guanyl-nucleotide exchange factor activity|
|regulation of TORC1 signaling|
|regulation of vacuole organization|
|neuron projection extension|
|cytoplasmic stress granule|
|positive regulation of macroautophagy|
|autophagosome|
|P-body|
|developmental cell growth|
|cell growth|
|regulation of TOR signaling|
|lysosomal transport|
|developmental growth involved in morphogenesis|
|positive regulation of autophagy|
|perikaryon|
|vacuolar transport|
|Rab GTPase binding|
|negative regulation of binding|
|regulation of macroautophagy|
|regulation of organelle assembly|
|ribonucleoprotein complex assembly|
|nuclear membrane|
|ribonucleoprotein complex subunit organization|
|lysosome|
|regulation of actin filament organization|
|process utilizing autophagic mechanism|
|autophagy|
|endosome|
|regulation of autophagy|
|regulation of actin cytoskeleton organization|
|regulation of supramolecular fiber organization|
|positive regulation of cellular catabolic process|
|axonogenesis|
|regulation of binding|
|developmental growth|
|regulation of actin filament-based process|
|growth|
|negative regulation of protein phosphorylation|
|axon development|
|dendrite|
|positive regulation of catabolic process|
|cell morphogenesis involved in neuron differentiation|
|negative regulation of phosphorylation|
|ribonucleoprotein complex biogenesis|
|neuron projection morphogenesis|
|plasma membrane bounded cell projection morphogenesis|
|cell projection morphogenesis|
|cell part morphogenesis|
|regulation of cytoskeleton organization|
|endocytosis|
|cell morphogenesis involved in differentiation|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|negative regulation of protein modification process|
|neuron projection development|
|import into cell|
|cell morphogenesis|
|organelle assembly|
|neuron development|
|cellular component morphogenesis|
|regulation of cellular catabolic process|
|cellular protein-containing complex assembly|
|regulation of cellular component biogenesis|
|regulation of catabolic process|
|neuron differentiation|
|negative regulation of cellular protein metabolic process|
|negative regulation of protein metabolic process|
|plasma membrane bounded cell projection organization|
|negative regulation of molecular function|
|cell projection organization|
|regulation of organelle organization|
|regulation of protein phosphorylation|
|generation of neurons|
|protein-containing complex assembly|
|regulation of phosphorylation|
|extracellular space|
|neurogenesis|
|cell development|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|cellular catabolic process|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|vesicle-mediated transport|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp434|Vemurafenib 6.6μM R08 exp434]]|-2.56|
|[[:results:exp89|Vemurafenib 6.6μM R02 exp89]]|-1.74|
|[[:results:exp95|BI-2536 0.0042μM R03 exp95]]|-1.73|
|[[:results:exp528|TGF-beta1 44ng/ml R08 exp528]]|1.8|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 18180
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 3.61 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='C9orf72 Expression in NALM6 Cells: 7.72'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>