''KRAS'' (

Kirsten Kirsten may refer to: * Kirsten (given name) * Kirsten (surname) * Hurricane Kirsten (disambiguation), two tropical cyclones in the Eastern Pacific Ocean See also * Kirsteen * Kirst * Kristen * Kirsty Kirsty or Kirstie is a feminine giv ...

rat

sarcoma A sarcoma is a rare type of cancer that arises from cells of mesenchymal origin. Originating from mesenchymal cells means that sarcomas are cancers of connective tissues such as bone, cartilage, muscle, fat, or vascular tissues. Sarcom ...

virus) is a gene that provides instructions for making a protein called K-Ras, a part of the

RAS/MAPK pathway The MAPK/ERK pathway (also known as the Ras-Raf-MEK-ERK pathway) is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. The signal starts when a signaling m ...

. The protein relays signals from outside the cell to the cell's nucleus. These signals instruct the cell to grow and divide ( proliferate) or to mature and take on specialized functions ( differentiate). It is called ''KRAS'' because it was first identified as a viral

oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

in the Kirsten RAt Sarcoma virus. The oncogene identified was derived from a cellular genome, so , when found in a cellular genome, is called a

proto-oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

. The K-Ras protein is a

GTPase GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a ...

, a class of

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

s which convert the

nucleotide Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...

guanosine triphosphate (GTP) into guanosine diphosphate (GDP). In this way the K-Ras protein acts like a

switch In electrical engineering, a switch is an electrical component that can disconnect or connect the conducting path in an electrical circuit, interrupting the electric current or diverting it from one conductor to another. The most common type o ...

that is turned on and off by the GTP and GDP molecules. To transmit signals, it must be turned on by attaching (binding) to a molecule of GTP. The K-Ras protein is turned off (inactivated) when it converts the GTP to GDP. When the protein is bound to GDP, it does not relay signals to the nucleus. The

gene product A gene product is the biochemical material, either RNA or protein, resulting from the expression of a gene. A measurement of the amount of gene product is sometimes used to infer how active a gene is. Abnormal amounts of gene product can be corre ...

of ''KRAS'', the K-Ras protein, was first found as a p21 GTPase. Like other members of the

ras subfamily Ras, from "Rat sarcoma virus", is a family of related proteins that are expressed in all animal cell lineages and organs. All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signal ...

of GTPases, the K-Ras protein is an early player in many

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...

pathways. K-Ras is usually tethered to

cell membranes The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extra ...

because of the presence of an

isoprene Isoprene, or 2-methyl-1,3-butadiene, is a common volatile organic compound with the formula CH2=C(CH3)−CH=CH2. In its pure form it is a colorless volatile liquid. It is produced by many plants and animals (including humans) and its polymers ar ...

group on its

C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein Proteins are large biomolecules and macromolecules that comp ...

. There are two protein products of the ''KRAS'' gene in mammalian cells that result from the use of alternative

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...

4 (exon 4A and 4B respectively): K-Ras4A and K-Ras4B. These proteins have different structures in their C-terminal region and use different mechanisms to localize to cellular membranes, including the

plasma membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

Function

''KRAS'' acts as a molecular on/off switch, using

protein dynamics In molecular biology, proteins are generally thought to adopt unique structures determined by their amino acid sequences. However, proteins are not strictly static objects, but rather populate ensembles of (sometimes similar) conformations. Tran ...

. Once it is

allosterically In the fields of biochemistry and pharmacology an allosteric regulator (or allosteric modulator) is a substance that binds to a site on an enzyme or receptor distinct from the active site, resulting in a conformational change that alters the p ...

activated, it recruits and activates proteins necessary for the propagation of

growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for ...

s, as well as other

cell signaling In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...

receptors like

c-Raf RAF proto-oncogene serine/threonine-protein kinase, also known as proto-oncogene c-RAF or simply c-Raf or even Raf-1, is an enzyme that in humans is genetic code, encoded by the ''RAF1'' gene. The c-Raf protein is part of the MAPK/ERK pathway, E ...

and

PI 3-kinase Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which i ...

. KRAS upregulates the

GLUT1 Glucose transporter 1 (or GLUT1), also known as solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1), is a uniporter protein that in humans is encoded by the ''SLC2A1'' gene. GLUT1 facilitates the transport of glucose acro ...

glucose transporter, thereby contributing to the Warburg effect in cancer cells. KRAS binds to GTP in its active state. It also possesses an intrinsic enzymatic activity which cleaves the terminal phosphate of the nucleotide, converting it to

GDP Gross domestic product (GDP) is a monetary measure of the total market value of all the final goods and services produced and rendered in a specific time period by a country or countries. GDP is often used to measure the economic performance o ...

. Upon conversion of GTP to GDP, KRAS is deactivated. The rate of conversion is usually slow, but can be increased dramatically by an accessory protein of the

GTPase-activating protein GTPase-activating proteins or GTPase-accelerating proteins (GAPs) are a family of regulatory proteins whose members can bind to activated G proteins and stimulate their GTPase activity, with the result of terminating the signaling event. GAPs are a ...

(GAP) class, for example

RasGAP RAS p21 protein activator 1 or RasGAP (Ras GTPase activating protein), also known as RASA1, is a 120-kDa cytosolic human protein that provides two principal activities: * Inactivation of Ras (protein), Ras from its active Guanosine triphosphate, ...

. In turn, KRAS can bind to proteins of the

Guanine Nucleotide Exchange Factor Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structu ...

(GEF) class (such as

SOS1 Son of sevenless homolog 1 is a protein that in humans is encoded by the ''SOS1'' gene. Function SOS1 is a guanine nucleotide exchange factor (GEF) which interacts with Ras protein, Ras proteins to phosphorylate GDP into GTP, or from an inacti ...

), which forces the release of bound nucleotide (GDP). Subsequently, KRAS binds GTP present in the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

and the GEF is released from ras-GTP. Other members of the Ras family include:

HRAS GTPase HRas, from "Harvey Rat sarcoma virus", also known as transforming protein p21 is an enzyme that in humans is encoded by the gene. The ''HRAS'' gene is located on the short (p) arm of chromosome 11 (human), chromosome 11 at position 15.5, ...

and NRAS. These proteins all are regulated in the same manner and appear to differ in their sites of action within the cell.

Clinical significance when mutated

This

proto-oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

is a Kirsten ras

oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

homolog from the mammalian Ras gene family. A single amino acid substitution, and in particular a single nucleotide 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 The pancreas (plural pancreases, or pancreata) is an Organ (anatomy), organ of the Digestion, digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a ...

and

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...

. Several

germline In biology and genetics, the germline is the population of a multicellular organism's cells that develop into germ cells. In other words, they are the cells that form gametes ( eggs and sperm), which can come together to form a zygote. They dif ...

KRAS mutations have been found to be associated with

Noonan syndrome Noonan syndrome (NS) is a genetic disorder that may present with mildly unusual facial features, short height, congenital heart disease, bleeding problems, and skeletal malformations. Facial features include widely spaced eyes, light-colored ...

and cardio-facio-cutaneous syndrome.

Somatic Somatic may refer to: * Somatic (biology), referring to the cells of the body in contrast to the germ line cells ** Somatic cell, a non-gametic cell in a multicellular organism * Somatic nervous system, the portion of the vertebrate nervous syst ...

''KRAS'' mutations are found at high rates in

leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...

s, colorectal cancer,

pancreatic cancer Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of ...

and

lung cancer Lung cancer, also known as lung carcinoma, is a malignant tumor that begins in the lung. Lung cancer is caused by genetic damage to the DNA of cells in the airways, often caused by cigarette smoking or inhaling damaging chemicals. Damaged ...

Colorectal cancer

The impact of KRAS mutations is heavily dependent on the order of mutations. Primary ''KRAS'' mutations generally lead to a self-limiting hyperplastic or borderline lesion, but if they occur after a previous APC mutation it often progresses to cancer. KRAS mutations are more commonly observed in cecal cancers than colorectal cancers located in any other places from ascending colon to rectum. As of 2006, KRAS mutation was predictive of a very poor response to

panitumumab Panitumumab, sold under the brand name Vectibix, is a fully human monoclonal antibody specific to the epidermal growth factor receptor (also known as ''EGF receptor'', ''EGFR'', ''ErbB-1'' and ''HER1'' in humans). Panitumumab is manufactured by ...

(Vectibix) and

cetuximab Cetuximab, sold under the brand name Erbitux, is an epidermal growth factor receptor (EGFR) inhibitor medication used for the treatment of metastatic colorectal cancer and head and neck cancer. Cetuximab is a chimeric (mouse/human) monoclonal a ...

(Erbitux) therapy in colorectal cancer. As of 2008, the most reliable way to predict whether a colorectal cancer patient will respond to one of the EGFR-inhibiting drugs was to test for certain “activating” mutations in the gene that encodes KRAS, which occurs in 30%–50% of colorectal cancers. Studies show patients whose tumors express the mutated version of the ''KRAS'' gene will not respond to cetuximab or panitumumab. As of 2009, although presence of the wild-type (or normal) ''KRAS'' gene does not guarantee that these drugs will work, a number of large studies had shown that cetuximab had efficacy in mCRC patients with KRAS wild-type tumors. In the Phase III CRYSTAL study, published in 2009, patients with the wild-type ''KRAS'' gene treated with Erbitux plus chemotherapy showed a response rate of up to 59% compared to those treated with chemotherapy alone. Patients with the ''KRAS'' wild-type gene also showed a 32% decreased risk of disease progression compared to patients receiving chemotherapy alone. As of 2012, it was known that emergence of KRAS mutations was a frequent driver of acquired resistance to

anti-EGFR therapy in colorectal cancers. The emergence of KRAS mutant clones can be detected non-invasively months before radiographic progression. It suggests to perform an early initiation of a

MEK inhibitor A MEK inhibitor is a chemical or drug that inhibits the mitogen-activated protein kinase enzymes MEK1 and/or MEK2. They can be used to affect the MAPK/ERK pathway which is often overactive in some cancers. (See MAPK/ERK pathway#Clinical signifi ...

as a rational strategy for delaying or reversing drug resistance.

''KRAS'' amplification

''KRAS'' gene can also be amplified in colorectal cancer and tumors harboring this genetic lesion are not responsive to EGFR inhibitors. Although KRAS amplification is infrequent in colorectal cancer, as of 2013 it was hypothesized to be responsible for precluding response to anti- EGFR treatment in some patients. As of 2015 amplification of wild-type Kras has also been observed in ovarian, gastric, uterine, and lung cancers.

Lung cancer

Whether a patient is positive or negative for a mutation in the

epidermal growth factor receptor The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor (biochemistry), receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligand (biochemistry ...

(EGFR) will predict how patients will respond to certain EGFR antagonists such as

erlotinib Erlotinib, sold under the brand name Tarceva among others, is a medication used to treat non-small cell lung cancer (NSCLC) and pancreatic cancer. Specifically it is used for NSCLC with mutations in the epidermal growth factor receptor (EGFR) ...

(Tarceva) or

gefitinib Gefitinib, sold under the brand name Iressa, is a medication used for certain breast, lung and other cancers. Gefitinib is an EGFR inhibitor, like erlotinib, which interrupts signaling through the epidermal growth factor receptor (EGFR) in targe ...

(Iressa). Patients who harbor an EGFR mutation have a 60% response rate to erlotinib. However, the mutation of KRAS and EGFR are generally mutually exclusive. Lung cancer patients who are positive for KRAS mutation (and the EGFR status would be wild type) have a low response rate to erlotinib or gefitinib estimated at 5% or less. Different types of data including mutation status and gene expression did not have a significant prognostic power. No correlation to survival was observed in 72% of all studies with KRAS sequencing performed in non-small cell lung cancer (NSCLC). However, KRAS mutations can not only affect the gene itself and the expression of the corresponding protein, but can also influence the expression of other downstream genes involved in crucial pathways regulating cell growth, differentiation and apoptosis. The different expression of these genes in ''KRAS''-mutant tumors might have a more prominent role in affecting patient's clinical outcomes. A 2008 paper published in ''

Cancer Research Cancer research is research into cancer to identify causes and develop strategies for prevention, diagnosis, treatment, and cure. Cancer research ranges from epidemiology, molecular bioscience to the performance of clinical trials to evaluate ...

'' concluded that the in vivo administration of the compound oncrasin-1 "suppressed the growth of K-ras mutant human lung tumor

xenografts Xenotransplantation (''xenos-'' from the Greek meaning "foreign" or strange), or heterologous transplant, is the transplantation of living cells, tissues or organs from one species to another.

Pancreatic cancer

Over 90% of pancreatic ductal adenocarcinomas (PDACs) have a KRAS mutation. There is one approved drug,

sotorasib Sotorasib, sold under the brand names Lumakras and Lumykras, is an anti-cancer medication used to treat non-small-cell lung cancer. It targets a specific mutation, G12C, in the protein K-Ras encoded by gene KRAS which is responsible for vario ...

, that targets the KRAS G12C mutation, but only ~1% of PDACs have this mutation. Another KRAS inhibitor, MRTX1133 targets G12D mutation which is present in over 40% of PDACs is currently in clinical trials to treat solid tumors including pancreatic adenocarcinoma.

''KRAS'' testing

In July 2009, the US Food and Drug Administration (FDA) updated the labels of two anti- EGFR

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodie ...

drugs indicated for treatment of metastatic colorectal cancer,

(Vectibix) and

(Erbitux), to include information about ''KRAS'' mutations. In 2012, the FDA cleared a genetic test by

QIAGEN QIAGEN N.V. is a German-founded multinational provider of sample and assay technologies for molecular diagnostics, applied testing, academic research, and pharmaceutical research. The company operates in more than 35 offices in over 25 countries ...

named therascreen ''KRAS'' test, designed to detect the presence of seven mutations in the ''KRAS'' gene in colorectal cancer cells. This test aids physicians in identifying patients with metastatic colorectal cancer for treatment with Erbitux. The presence of KRAS mutations in colorectal cancer tissue indicates that the patient may not benefit from treatment with Erbitux. If the test result indicates that the KRAS mutations are absent in the colorectal cancer cells, then the patient may be considered for treatment with Erbitux.

As a therapeutic target

As of 2014, driver mutations in KRAS were known to underlie the pathogenesis of up to 20% of human cancers. Hence KRAS is an attractive drug target, but as of 2018 lack of obvious binding sites had hindered pharmaceutical development. One potential drug interaction site is where GTP/GDP binds, but due to the extraordinarily high affinity of GTP/GDP for this site, it appeared unlikely as of 2018 that drug-like

small molecule In molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs are small molecules; ...

inhibitors could compete with GTP/GDP binding. Other than where GTP/GDP binds, there are no obvious high affinity binding sites for small molecules.

G12C mutation

KRAS protein G12C mutant with GDP and sotorasib 6OIM

One fairly frequent driver mutation is KRAS^G12C which is adjacent a shallow binding site. As of 2019, this allowed the development of

electrophilic In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively charged, have an atom that carr ...

KRAS inhibitors that can form irreversible

covalent bond A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atom ...

s with

nucleophilic In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they a ...

sulfur atom of Cys-12 and hence selectively target KRAS^G12C and leave wild-type KRAS untouched. In 2021, the U.S. FDA approved one KRAS^G12C mutant covalent inhibitor,

(AMG 510,

Amgen Amgen Inc. (formerly Applied Molecular Genetics Inc.) is an American multinational biopharmaceutical Corporation, company headquartered in Thousand Oaks, California. As one of the world's largest independent biotechnology companies, Amgen has a ...

) for the treatment of

non-small cell lung cancer Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitiv ...

(NSCLC), the first KRAS inhibitor to reach the market and enter clinical use. A second is adagrasib (MRTX-849, Mirati Therapeutics) while JNJ-74699157 (also known as ARS-3248, Wellspring Biosciences/ Janssen) has received an

investigational new drug The United States Food and Drug Administration's Investigational New Drug (IND) program is the means by which a pharmaceutical industry, pharmaceutical company obtains permission to start human clinical trials and to ship an experimental drug inte ...

(IND) approval to start clinical trials. An

antisense oligonucleotide Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, research, and forensics. Commonly made in the laboratory by solid-phase chemical synthesis, these small fragments of nucleic aci ...

(ASO) targeting KRAS, AZD4785 (

AstraZeneca AstraZeneca plc () (AZ) is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, UK. It has a portfolio of products for major diseases in areas includi ...

/ Ionis Therapeutics), completed a phase I study but in 2019 was discontinued from further development because of insufficient knockdown of the target. A phase Ia/Ib dose escalation trial of the oral selective ''KRAS'' G12C inhibitor divarasib was published in 2023, where the drug was tested in non-small cell lung cancer, colorectal cancer, and other solid tumors with ''KRAS'' G12C mutations. It continues in phase I and II studies for several cancer types as of August 2023.

G12D mutation

The most common ''KRAS'' mutation is G12D which is estimated to be present in up to 37% pancreatic cancers and over 12% of colorectal cancers. Normally amino acid position 12 of the KRAS protein is occupied by glycine but in G12D it is occupied by aspartic acid. As of 2023, there are no commercial drug candidates targeting the ''KRAS'' G12D mutation in the clinical phase of development. A novel inhibitor finding strategy for mutated G12D KRAS molecules was described in. The KRAS mutations in the 12th residue position inhibit the bound of the regulatory GAP molecule to the mutated KRAS, causing uncontrolled cell growth. The novel strategy proposes finding small glue molecules, which attach the mutated KRAS to the GAP, prohibiting uncontrolled cell growth and restoring the normal function. For this goal a theoretical KRAS-GAP conformation was designed with a several Å gap between the molecules, and a high-throughput in silico docking was performed for finding gluing agents. As a proof of concept, two novel molecules were described with satisfying biological activity. As of 2021, there were a number of drug candidates in preclinical stages of development targeting the KRAS G12D mutation. Mirati therapeutics has stated it was seeking

(IND) approval in H1:2021 to start clinical trials. As of 2022 Revolution Medicines was exploring a small molecule therapy and reported anti-tumor activity in KRAS-G12D mutant tumor models. In 2021, the first clinical trial of a gene therapy targeting KRAS G12D was recruiting patients, sponsored by the

National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...

. In June 2022, a case report was published about a 71-year-old woman with metastatic pancreatic cancer after extensive treatment ( Whipple Surgery, radiation and multiple agent chemotherapy) who received a single infusion of her blood with engineered T cells with 2 genes encoding T cell receptors, directed to both the G12D mutation and an HLA allele (

HLA-C HLA-C (Human Leukocyte Antigen-C) belongs to the MHC class I heavy chain receptors. The C receptor is a heterodimer consisting of a HLA-C mature gene product and β2-microglobulin. The mature C chain is anchored in the membrane. MHC Class I mole ...

*08:02). Her tumor regressed persistently. But another similarly treated patient died from the cancer.

Interactions

KRAS has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with: *

C-Raf RAF proto-oncogene serine/threonine-protein kinase, also known as proto-oncogene c-RAF or simply c-Raf or even Raf-1, is an enzyme that in humans is genetic code, encoded by the ''RAF1'' gene. The c-Raf protein is part of the MAPK/ERK pathway, E ...

, * PIK3CG, *

RALGDS Ral guanine nucleotide dissociation stimulator is a protein that is encoded by the ''RALGDS'' gene in humans. Interactions RALGDS has been shown to interact with: * Arrestin beta 1, * Arrestin beta 2, * HRAS, * KRAS, * MRAS, * RAP1A, ...

, and * RASSF2. *

Calmodulin Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all Eukaryote, eukaryotic cells. It is an intracellular target of the Second messenger system, sec ...

References

External links

KRAS Reference Standards
- Learn more about KRAS Reference Controls
GeneReviews/NCBI/NIH/UW entry on Cardiofaciocutaneous Syndrome

GeneReviews/NCBI/NIH/UW entry on Noonan syndrome
* * {{Acid anhydride hydrolases Oncogenes