The KRAS gene provides instructions for making a protein called K-Ras that is part of a signaling pathway known as the RAS/MAPK pathway. 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). The K-Ras protein is a GTPase, which means it converts a molecule called GTP into another molecule called GDP. In this way the K-Ras protein acts like a switch 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 cell's nucleus. The KRAS gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous. The KRAS gene is in the Ras family of oncogenes, which also includes two other genes: HRAS and NRAS. These proteins play important roles in cell division, cell differentiation, and the self-destruction of cells (apoptosis).

Biomarkers

Molecular markers used to guide treatment, assess prognosis, or detect relapse.

• BRAF
• BRCA
• EGFR
• HER2
• KRAS
• ROS1
• ALK
• PD-L1

KRAS

May 29, 2019

CRISPR Framework Helps Identify Combination Therapies for Optimal Targeting of KRAS Mutant

Researchers used a genome-scale CRISPRi platform to identify genetic interactions with an inhibitor for a mutant form of KRAS in models of lung and pancreatic cancer.

Feb 26, 2019

Thermo Fisher Scientific Oncomine Dx Target Test Gets Expanded Regulatory Approval in Japan

The NGS assay is designed to help physicians to identify non-small cell lung cancer patients who may benefit from eight targeted therapies.

Oct 31, 2018

Lung Cancer Panel From PlexBio Receives CE Mark

The assay can identify KRAS, NRAS, PIK3CA, BRAF, and EGFR gene mutations, as well as 19 gene rearrangements of the ALK, ROS1, RET, NTRK1, and MET genes from FFPE.

Oct 17, 2018

Thermo Fisher Scientific Gets CE-IVD Mark for NGS Cancer Test

The test is designed to detect cancer-driver gene variants associated with certain targeted solid tumor therapies, and is validated as a companion diagnostic.

Sep 27, 2018

UK Group Develops Cancer Liquid Biopsy Assay to Detect Low-Level Mutations

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The group plans to use the assay for translational studies on metastasis and drug resistance initially and to develop a clinical version later on.

Oct 17, 2017

AstraZeneca Publishes Head-to-Head Study of 13 KRAS Mutation Detection Technologies

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The recent study highlights strengths and weaknesses of numerous platforms and may help end users choose the best assay for their circumstances.

May 13, 2016

Colorectal Cancer Patients' Cetuximab Response Can Be Discerned From FCGR2A Genotype

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Results from a recent study clarify some conflicting prior determinations, and provide a new rationale to further explore the FCGR2A biomarker in prospective trials.

May 11, 2015

FDA Approves Roche KRAS Mutation Test for Metastatic Colorectal Cancer Patients

The test helps to identify metastatic colorectal cancer patients for whom treatment with Erbitux (cetuximab) or Vectibix (panitumumab) may be effective because their tumors carry no KRAS mutations.

Mar 30, 2015

CAP, AMP Among Groups Jointly Issuing Colorectal Cancer Molecular Testing Draft Recommendations

The draft document, which includes recommendations on which molecular tests labs should perform, on what samples, and with what analytical specifications, is available for comment until April 22.

KRAS gene

KRAS proto-oncogene, GTPase

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 Normal Function

The KRAS gene provides instructions for making a protein called K-Ras that is part of a signaling pathway known as the RAS/MAPK pathway. 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). The K-Ras protein is a GTPase, which means it converts a molecule called GTP into another molecule called GDP. In this way the K-Ras protein acts like a switch 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 cell's nucleus.

The KRAS gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous. The KRAS gene is in the Ras family of oncogenes, which also includes two other genes: HRAS and NRAS. These proteins play important roles in cell division, cell differentiation, and the self-destruction of cells (apoptosis).

Related Information

• What is DNA?
• What is a gene?
• How do genes direct the production of proteins?
• More about How Genes Work

 Health Conditions Related to Genetic Changes

 Cardiofaciocutaneous syndrome

Mutations in the KRAS gene are an uncommon cause of cardiofaciocutaneous syndrome, accounting for less than 5 percent of cases. Several mutations in the KRAS gene have been identified in people with characteristic features of the disorder, which include heart defects, distinctive facial features, and skin abnormalities. These mutations are present in all of the body's cells and are known as germline mutations. The mutations change single protein building blocks (amino acids) in the K-Ras protein. The altered protein shows increased GTP binding and a decreased ability to convert GTP to GDP. These effects lead to prolonged activation of the K-Ras protein, which alters tightly regulated RAS/MAPK signaling during development. The altered signaling interferes with the development of organs and tissues throughout the body, leading to the varied signs and symptoms of cardiofaciocutaneous syndrome.

More About This Health Condition

 Noonan syndrome

Genetics Home Reference provides information about Noonan syndrome.

More About This Health Condition

 Autoimmune lymphoproliferative syndrome

Genetics Home Reference provides information about autoimmune lymphoproliferative syndrome.

More About This Health Condition

 Cholangiocarcinoma

Genetics Home Reference provides information about cholangiocarcinoma.

More About This Health Condition

 Core binding factor acute myeloid leukemia

Genetics Home Reference provides information about core binding factor acute myeloid leukemia.

More About This Health Condition

 Epidermal nevus

Genetics Home Reference provides information about epidermal nevus.

More About This Health Condition

 Lung cancer

At least three mutations in the KRAS gene have been associated with lung cancer. Lung cancer is a disease in which certain cells in the lungs become abnormal and multiply uncontrollably to form a tumor. Lung cancer may not cause signs or symptoms in its early stages. These KRASgene mutations are somatic, which means they are acquired during a person's lifetime and are present only in tumor cells. Somatic mutations are not inherited. Nearly all of the KRAS gene mutations associated with lung cancer change the amino acid glycine at position 12 or 13 (Gly12 or Gly13) or change the amino acid glutamine at position 61 (Gln61) in the K-Ras protein. These mutations result in a K-Ras protein that is constantly turned on (constitutively activated) and directing cells to proliferate in an uncontrolled way, which leads to tumor formation. When these genetic changes occur in cells in the lungs, lung cancer can develop.

KRAS gene mutations are found in 15 to 25 percent of all lung cancer cases but are more frequent in white populations than in Asian populations; 25 to 50 percent of whites with lung cancer have KRAS gene mutations, whereas 5 to 15 percent of Asians with lung cancer have KRAS gene mutations.

KRAS gene mutations are much more common in long-term tobacco smokers with lung cancer than in nonsmokers. Lung cancers with KRAS gene mutations typically indicate a poor prognosis and are associated with resistance to several cancer treatments.

More About This Health Condition

 Other disorders

Germline mutations in the KRAS gene also cause a disorder whose major features overlap with those of cardiofaciocutaneous syndrome (described above) and two related disorders called Noonan syndrome and Costello syndrome. This condition has been described as the KRASmutation-associated phenotype. People with this condition have variable signs and symptoms that include mild to moderate intellectual disability, distinctive facial features, short stature, an unusually large head (macrocephaly), and hair that is sparse and thin.

At least nine mutations in the KRAS gene have been reported in people with this disorder. Each of these mutations changes single amino acids in the K-Ras protein. These genetic changes abnormally activate the protein, which alters chemical signaling in cells throughout the body. The altered signaling interferes with the normal development of many organs and tissues, resulting in the characteristic features of the KRAS mutation-associated phenotype.

 Other cancers

Somatic mutations in the KRAS gene are involved in the development of several types of cancer, particularly pancreatic and colorectal cancers. These mutations lead to a K-Ras protein that is more strongly overactivated than the mutations that cause cardiofaciocutaneous syndrome (described above). The abnormal K-Ras protein is always active and can direct cells to proliferate in an uncontrolled way.

Related Information

• What is a gene mutation and how do mutations occur?
• What kinds of gene mutations are possible?
• More about Mutations and Health

 Chromosomal Location

Cytogenetic Location: 12p12.1, which is the short (p) arm of chromosome 12 at position 12.1

Molecular Location: base pairs 25,204,789 to 25,251,003 on chromosome 12 (Homo sapiens Annotation Release 109, GRCh38.p12) (NCBI)

Credit: Genome Decoration Page/NCBI

Related Information

• How do geneticists indicate the location of a gene?

 Other Names for This Gene

• C-K-RAS
• c-K-ras protein
• c-K-ras2 protein
• c-Kirsten-ras protein
• cellular c-Ki-ras2 proto-oncogene
• K-ras p21 protein
• KI-RAS
• Kirsten rat sarcoma viral oncogene homolog
• KRAS1
• PR310 c-K-ras oncogene
• RASK2
• RASK_HUMAN
• transforming protein p21
• v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog

Related Information

• How are genetic conditions and genes named?

 Additional Information & Resources

 Educational Resources (4 links)

• Genomes (second edition, 2002): Signal Transduction with Many Steps Between Receptor and Genome
• Immunobiology: The Immune System in Health and Disease (fifth edition, 2001): Small G Proteins Activate a Protein Kinase Cascade That Transmits the Signal to the Nucleus
• Molecular Biology of the Cell (fourth edition, 2002): MAP Kinase Pathways
• Molecular Biology of the Cell (fourth edition, 2002): Ras Is Activated by a Guanine Nucleotide Exchange Factor

 Clinical Information from GeneReviews (3 links)

• Cardiofaciocutaneous Syndrome
• Costello Syndrome
• Noonan Syndrome

 Tests Listed in the Genetic Testing Registry (1 link)

• Tests of KRAS

 Scientific Articles on PubMed (1 link)

• PubMed

 Catalog of Genes and Diseases from OMIM (3 links)

• COLORECTAL CANCER
• PANCREATIC CANCER
• V-KI-RAS2 KIRSTEN RAT SARCOMA VIRAL ONCOGENE HOMOLOG

 Research Resources (7 links)

• Atlas of Genetics and Cytogenetics in Oncology and Haematology
• Cancer Genetics Web
• ClinVar
• HGNC Gene Symbol Report
• Monarch Initiative
• NCBI Gene
• UniProt

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