C9ORF72 — C9orf72-SMCR8 complex subunit
C9ORF72 belongs to a gene co-expression module in 4 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
C9ORF72's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| CD19⁺ B cells | Hypoxia/metabolic stress Stress | ALG13, ARL4A, HIP1R, PDE4B, SC5D, SLC2A3, TENT5C, VPS37B +2 more | View in SCUBA |
| CD4⁺ T cells | Immediate early activation TCR/AP1/NFKb pathway | ALG13, AREG, BCAS2, CXCR4, FAM222A, HIP1R, NR4A2, PABPC1 +18 more | View in SCUBA |
| Macrophages | Sphingolipid Membrane Homeostasis Lipid metabolism | ACER3, AGPAT3, ARHGEF11, ATP2A2, CMIP, DMXL2, DOCK8, FOXN2 +12 more | View in SCUBA |
| Neutrophils | NF-κB Inflammatory Transcription Inflammatory | BID, DENND5A, ELL2, ETF1, N4BP1, NFE2L2, NFKB1, OXSR1 +10 more |
About the gene
| Synonyms | DENND9, DENNL72, MGC23980 |
|---|---|
| Chromosome | 9: 27535640-27573866 |
| Predicted location | Intracellular |
| Essential gene | No |
| Protein class | Disease related genes, Human disease related genes, Predicted intracellular proteins |
| Molecular function | Guanine-nucleotide releasing factor |
| Biological process | Autophagy |
Function
Acts as a guanine-nucleotide releasing factor (GEF) for Rab GTPases by promoting the conversion of inactive RAB-GDP to the active form RAB-GTP. Acts as a GEF for RAB39A which enables HOPS-mediated autophagosome-lysosome membrane tethering and fusion in mammalian autophagy. Component of the C9orf72-SMCR8 complex where both subunits display GEF activity and that regulates autophagy. As part of the C9orf72-SMCR8-WDR41 (CSW) complex, functions as GEF for RAB8A and RAB39B, thereby promoting autophagosome maturation. As part of the C9orf72-SMCR8 complex, also functions as GTPase activating protein (GAP) for RAB8A and RAB11A in vitro. The C9orf72-SMCR8 complex also acts as a regulator of autophagy initiation by interacting with the ULK1/ATG1 kinase complex and modulating its protein kinase activity. Promotes initiation of autophagy by regulating the RAB1A-dependent trafficking of the ULK1/ATG1 kinase complex to the phagophore which leads to autophagosome formation. Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates. Plays a role in endosomal trafficking. May be involved in regulating the maturation of phagosomes to lysosomes (By similarity). Promotes the lysosomal localization and lysosome-mediated degradation of CARM1 which leads to inhibition of starvation-induced lipid metabolism (By similarity). Regulates actin dynamics in motor neurons by inhibiting the GTP-binding activity of ARF6, leading to ARF6 inactivation. This reduces the activity of the LIMK1 and LIMK2 kinases which are responsible for phosphorylation and inactivation of cofilin, leading to CFL1/cofilin activation. Positively regulates axon extension and axon growth cone size in spinal motor neurons. Required for SMCR8 protein expression and localization at pre- and post-synaptic compartments in the forebrain, also regulates protein abundance of RAB3A and GRIA1/GLUR1 in post-synaptic compartments in the forebrain and hippocampus (By similarity). Plays a role within the hematopoietic system in restricting inflammation and the development of autoimmunity (By similarity). Regulates stress granule assembly in response to cellular stress. Does not play a role in regulation of stress granule assembly in response to cellular stress
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.