ras遺伝子によりコードされる低分子量GTP結合タンパク質。哺乳動物ではH-Ras, K-Ras, N-Rasの三種類で分子量は21000。
Ｃ末端から４番目のシステインにファルネシル化が起こり、残り三つのアミノ酸が切り取られ、システインのカルボキシ基がカルボキシメチル化される。
１分子当たり１分子のGTPまたはGDPと結合しており、結合したGTPを加水分解する活性をもつ。
GTPが結合したRasが活性型で、RafからMAPキナーゼに至るセリントレオニンキナーゼカスケードを直接制御する。
従って、GTP加水分解活性の低下、およびGDP結合親和性が低下する変異を持つRasは細胞増殖制御に異常をきたす。
多くの細胞増殖因子のシグナル経路との一部と成っており、Rasに入るシグナルの経路として、
受容体チロシンキナーゼ＞アダプタータンパク（Grb2）＞グアニンヌクレオチド交換因子（Sos）＞Ras
が知られている。
Rasのシグナルを受け取る側として、Raf以外にも、ホスファチジルイノシトール3-キナーゼ(PI3K）、ホスホリパーゼCεなどが知られている。
がんとの関わり
KRAS
Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.25
Leukemia, juvenile myelomonocytic (JMML) [MIM:607785]: An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages.
Note: The disease is caused by mutations affecting the gene represented in this entry.
Noonan syndrome 3 (NS3) [MIM:609942]: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.28 Ref.31 Ref.33 Ref.34 Ref.35 Ref.36
Gastric cancer (GASC) [MIM:613659]: A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.24 Ref.26
Defects in KRAS are a cause of pylocytic astrocytoma (PA). Pylocytic astrocytomas are neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors. Ref.23
Cardiofaciocutaneous syndrome 2 (CFC2) [MIM:615278]: A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. CFC2 patients often do not have the skin abnormalities, such as ichthyosis, hyperkeratosis, and hemangioma observed in CFC1.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.30 Ref.31 Ref.34 Ref.36 Ref.37
KRAS mutations are involved in cancer development.
HRAS
- 膀胱がん
- 口腔がん
Faciocutaneoskeletal syndrome (FCSS) [MIM:218040]: A rare condition characterized by prenatally increased growth, postnatal growth deficiency, mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.28 Ref.45 Ref.46 Ref.47 Ref.48 Ref.50 Ref.51 Ref.52
Congenital myopathy with excess of muscle spindles (CMEMS) [MIM:218040]: Variant of Costello syndrome.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.49
Hurthle cell thyroid carcinoma (HCTC) [MIM:607464]: A rare type of thyroid cancer accounting for only about 3-10% of all differentiated thyroid cancers. These neoplasms are considered a variant of follicular carcinoma of the thyroid and are referred to as follicular carcinoma, oxyphilic type.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors.
Bladder cancer (BLC) [MIM:109800]: A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas that begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
Defects in HRAS are the cause of oral squamous cell carcinoma (OSCC). Ref.43
Schimmelpenning-Feuerstein-Mims syndrome (SFM) [MIM:163200]: A disease characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects. Many oral manifestations have been reported, not only including hypoplastic and malformed teeth, and mucosal papillomatosis, but also ankyloglossia, hemihyperplastic tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous nevi follow the lines of Blaschko and these can continue as linear intraoral lesions, as in mucosal papillomatosis.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.53
NRAS
Leukemia, juvenile myelomonocytic (JMML) [MIM:607785]: An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages.
Note: The disease is caused by mutations affecting the gene represented in this entry.
Noonan syndrome 6 (NS6) [MIM:613224]: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20
Autoimmune lymphoproliferative syndrome 4 (ALPS4) [MIM:614470]: A disorder of apoptosis, characterized by chronic accumulation of non-malignant lymphocytes, defective lymphocyte apoptosis, and an increased risk for the development of hematologic malignancies.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19
