KRAS(Kirsten rat sarcoma viral oncogene homolog)是一种原癌基因,属于RAS基因家族,该家族还包括HRAS和NRAS。RAS家族基因编码小GTP酶蛋白,在细胞信号传导中起关键作用,主要调控细胞增殖、分化和存活。KRAS蛋白在RAS-MAPK和PI3K-AKT等信号通路中作为分子开关,通过结合GTP(激活状态)或GDP(失活状态)传递生长因子受体的信号。KRAS的常见突变(如G12D、G12V、G13D)会导致其持续激活,无法水解GTP,从而促进细胞不受控增殖,与多种癌症密切相关,尤其是胰腺癌(90%突变率)、结直肠癌(40%)和肺癌(30%)。KRAS突变还影响肿瘤微环境,促进免疫逃逸。KRAS过表达会增强下游通路活性,加速肿瘤进展和转移;而敲低KRAS可抑制肿瘤生长,但可能影响正常组织(如造血系统)的稳态。KRAS的突变体(如G12C)已成为靶向治疗热点,相关抑制剂(如Sotorasib)通过共价结合突变位点阻断信号传导。KRAS还与代谢重编程相关,突变后会增强糖酵解(Warburg效应)。KRAS家族基因的共性是编码高度保守的GTP结合蛋白,均含效应结构域和膜定位信号,依赖翻译后修饰(如法尼基化)定位至细胞膜。KRAS的不同剪接变体(4A/4B)可能影响其功能特异性。由于KRAS在癌症中的核心作用,其调控机制和靶向策略是肿瘤研究的重要方向。
This gene, a Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid substitution is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region. [provided by RefSeq, Jul 2008]
本基因,姬ras癌基因来自哺乳动物ras基因家族同源物,编码的蛋白质,它是小GTP酶超家族的成员。单一氨基酸取代是负责活化突变。该成果转化蛋白在各种恶性肿瘤,包括肺腺癌,粘液瘤,胰腺和结直肠癌性导管癌牵连。选择性剪接导致变体编码两种亚型,在C-末端区域不同。 [由RefSeq的,2008年7月提供]
KRAS基因(以及对应的蛋白质)的细胞分布位置:
KRAS基因的本体(GO)信息:
| 名称 |
|---|
| 4014 Ras signaling pathway [PATH:hsa04014] |
| 4015 Rap1 signaling pathway [PATH:hsa04015] |
| 4010 MAPK signaling pathway [PATH:hsa04010] |
| 4012 ErbB signaling pathway [PATH:hsa04012] |
| 4370 VEGF signaling pathway [PATH:hsa04370] |
| 4068 FoxO signaling pathway [PATH:hsa04068] |
| 4071 Sphingolipid signaling pathway [PATH:hsa04071] |
| 4151 PI3K-Akt signaling pathway [PATH:hsa04151] |
| 4810 Regulation of actin cytoskeleton [PATH:hsa04810] |
| 4530 Tight junction [PATH:hsa04530] |
| 4540 Gap junction [PATH:hsa04540] |
| 4550 Signaling pathways regulating pluripotency of stem cells [PATH:hsa04550] |
| 4650 Natural killer cell mediated cytotoxicity [PATH:hsa04650] |
| 4660 T cell receptor signaling pathway [PATH:hsa04660] |
| 4662 B cell receptor signaling pathway [PATH:hsa04662] |
| 4664 Fc epsilon RI signaling pathway [PATH:hsa04664] |
| 4062 Chemokine signaling pathway [PATH:hsa04062] |
| 4910 Insulin signaling pathway [PATH:hsa04910] |
| 4912 GnRH signaling pathway [PATH:hsa04912] |
| 4915 Estrogen signaling pathway [PATH:hsa04915] |
| 4914 Progesterone-mediated oocyte maturation [PATH:hsa04914] |
| 4917 Prolactin signaling pathway [PATH:hsa04917] |
| 4921 Oxytocin signaling pathway [PATH:hsa04921] |
| 4919 Thyroid hormone signaling pathway [PATH:hsa04919] |
| 4916 Melanogenesis [PATH:hsa04916] |
| 4960 Aldosterone-regulated sodium reabsorption [PATH:hsa04960] |
| 4725 Cholinergic synapse [PATH:hsa04725] |
| 4726 Serotonergic synapse [PATH:hsa04726] |
| 4720 Long-term potentiation [PATH:hsa04720] |
| 4730 Long-term depression [PATH:hsa04730] |
| 4722 Neurotrophin signaling pathway [PATH:hsa04722] |
| 4320 Dorso-ventral axis formation [PATH:hsa04320] |
| 4360 Axon guidance [PATH:hsa04360] |
| 5200 Pathways in cancer [PATH:hsa05200] |
| 5230 Central carbon metabolism in cancer [PATH:hsa05230] |
| 5231 Choline metabolism in cancer [PATH:hsa05231] |
| 5206 MicroRNAs in cancer [PATH:hsa05206] |
| 5205 Proteoglycans in cancer [PATH:hsa05205] |
| 5203 Viral carcinogenesis [PATH:hsa05203] |
| 5210 Colorectal cancer [PATH:hsa05210] |
| 5212 Pancreatic cancer [PATH:hsa05212] |
| 5214 Glioma [PATH:hsa05214] |
| 5216 Thyroid cancer [PATH:hsa05216] |
| 5221 Acute myeloid leukemia [PATH:hsa05221] |
| 5220 Chronic myeloid leukemia [PATH:hsa05220] |
| 5218 Melanoma [PATH:hsa05218] |
| 5211 Renal cell carcinoma [PATH:hsa05211] |
| 5219 Bladder cancer [PATH:hsa05219] |
| 5215 Prostate cancer [PATH:hsa05215] |
| 5213 Endometrial cancer [PATH:hsa05213] |
| 5223 Non-small cell lung cancer [PATH:hsa05223] |
| 5034 Alcoholism [PATH:hsa05034] |
| 5166 HTLV-I infection [PATH:hsa05166] |
| 5161 Hepatitis B [PATH:hsa05161] |
| 5160 Hepatitis C [PATH:hsa05160] |
| 名称 |
|---|
| Activation of RAS in B cells |
| Adaptive Immune System |
| ARMS-mediated activation |
| Axon guidance |
| C-type lectin receptors (CLRs) |
| CD209 (DC-SIGN) signaling |
| Cell surface interactions at the vascular wall |
| Constitutive Signaling by EGFRvIII |
| Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants |
| Cytokine Signaling in Immune system |
| DAP12 interactions |
| DAP12 signaling |
| Developmental Biology |
| Disease |
| Diseases of signal transduction |
| Downstream signal transduction |
| Downstream signaling events of B Cell Receptor (BCR) |
| Downstream signaling of activated FGFR1 |
| Downstream signaling of activated FGFR2 |
| Downstream signaling of activated FGFR3 |
| Downstream signaling of activated FGFR4 |
| EGFR Transactivation by Gastrin |
| Fc epsilon receptor (FCERI) signaling |
| FCERI mediated MAPK activation |
| FRS-mediated FGFR1 signaling |
| FRS-mediated FGFR2 signaling |
| FRS-mediated FGFR3 signaling |
| Frs2-mediated activation |
| FRS2-mediated FGFR4 signaling |
| Gastrin-CREB signalling pathway via PKC and MAPK |
| GRB2 events in EGFR signaling |
| GRB2 events in ERBB2 signaling |
| Hemostasis |
| IGF1R signaling cascade |
| Immune System |
| Innate Immune System |
| Insulin receptor signalling cascade |
| Interleukin-2 signaling |
| IRS-mediated signalling |
| IRS-related events |
| IRS-related events triggered by IGF1R |
| MEK activation |
| NCAM signaling for neurite out-growth |
| NGF signalling via TRKA from the plasma membrane |
| p38MAPK events |
| Prolonged ERK activation events |
| RAF activation |
| RAF phosphorylates MEK |
| RAF/MAP kinase cascade |
| SHC-mediated cascade:FGFR1 |
| SHC-mediated cascade:FGFR2 |
| SHC-mediated cascade:FGFR3 |
| SHC-mediated cascade:FGFR4 |
| SHC-mediated signalling |
| SHC-related events |
| SHC-related events triggered by IGF1R |
| SHC1 events in EGFR signaling |
| SHC1 events in ERBB2 signaling |
| SHC1 events in ERBB4 signaling |
| Signal Transduction |
| Signaling by EGFR |
| Signaling by EGFR in Cancer |
| Signaling by EGFRvIII in Cancer |
| Signaling by ERBB2 |
| Signaling by ERBB4 |
| Signaling by FGFR |
| Signaling by FGFR in disease |
| Signaling by FGFR1 |
| Signaling by FGFR1 in disease |
| Signaling by FGFR1 mutants |
| Signaling by FGFR2 |
| Signaling by FGFR2 in disease |
| Signaling by FGFR2 mutants |
| Signaling by FGFR3 |
| Signaling by FGFR3 in disease |
| Signaling by FGFR3 mutants |
| Signaling by FGFR4 |
| Signaling by FGFR4 in disease |
| Signaling by FGFR4 mutants |
| Signaling by GPCR |
| Signaling by Insulin receptor |
| Signaling by Interleukins |
| Signaling by Leptin |
| Signaling by Ligand-Responsive EGFR Variants in Cancer |
| Signaling by PDGF |
| Signaling by SCF-KIT |
| Signaling by the B Cell Receptor (BCR) |
| Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) |
| Signaling by VEGF |
| Signalling by NGF |
| Signalling to ERKs |
| Signalling to p38 via RIT and RIN |
| Signalling to RAS |
| SOS-mediated signalling |
| Tie2 Signaling |
| VEGFA-VEGFR2 Pathway |
| VEGFR2 mediated cell proliferation |
| 疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
| Juvenile Myelomonocytic Leukemia | 0.447805801 | 12 | 3 | BeFree_CLINVAR_CTD_human_GAD_LHGDN_MGD_ORPHANET |
| NOONAN SYNDROME 3 | 0.44 | 3 | 14 | CLINVAR_CTD_human_MGD_UNIPROT |
| Colorectal Neoplasms | 0.322443416 | 95 | 1 | BeFree_CTD_human_GAD_LHGDN_RGD |
| Non-Small Cell Lung Carcinoma | 0.321301873 | 222 | 13 | BeFree_CLINVAR_CTD_human_GAD_LHGDN |
| Adenocarcinoma | 0.309144846 | 243 | 3 | BeFree_CTD_human_GAD_LHGDN |
| Noonan Syndrome | 0.264970109 | 33 | 2 | BeFree_CTD_human_GAD_LHGDN_ORPHANET |
| ovarian neoplasm | 0.255992664 | 20 | 2 | BeFree_CLINVAR_CTD_human_GAD_LHGDN |
| Stomach Neoplasms | 0.25581703 | 10 | 2 | BeFree_CLINVAR_CTD_human_GAD_LHGDN |
| Cardio-facio-cutaneous syndrome | 0.244071628 | 16 | 3 | BeFree_CTD_human_ORPHANET |
| Pilocytic Astrocytoma | 0.240542884 | 2 | 1 | BeFree_CLINVAR_ORPHANET |
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