V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)

What is the official name of the KRAS gene?

The official name of this gene is “v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog.”

KRAS is the gene's official symbol. The KRAS gene is also known by other names, listed below.

What is the normal function of the KRAS gene?

The KRAS gene provides instructions for making a protein called K-Ras that is involved primarily in regulating cell division. Through a process known as signal transduction, the protein relays signals from outside the cell to the cell's nucleus. These signals instruct the cell to grow and divide 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. The K-Ras protein acts like a switch, and it is turned on and off by the GTP and GDP molecules. To transmit signals, the K-Ras protein must be turned on by 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. KRAS is in the Ras family of oncogenes, which also includes two other genes: HRAS and NRAS. The proteins produced from these three genes are GTPases. These proteins play important roles in cell division, cell differentiation, and the self-destruction of cells (apoptosis).

How are changes in the KRAS gene related to health conditions?

Noonan syndrome - caused by mutations in the KRAS gene

Mutations in the KRAS gene have caused a small number of cases of severe or atypical Noonan syndrome. Intellectual disability is more common in people who have Noonan syndrome with a KRAS mutation than in people with Noonan syndrome caused by a mutation in a different gene.

Each of the KRAS mutations changes a single protein building block (amino acid) in a critical region of the K-Ras protein, which causes the protein to be continuously active. Instead of triggering cell growth in response to particular signals from outside the cell, the overactive protein directs cells to grow and divide constantly. During embryonic development, the overactive K-Ras protein disrupts the normal growth and maturation of certain tissues. Researchers believe that increased K-Ras activation leading to defective cell movement and differentiation could play a role in the signs and symptoms of Noonan syndrome, including short stature and facial abnormalities.

cancers - increased risk from variations of the KRAS gene

Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic mutations in the KRAS gene are involved in the development of several types of cancer. These mutations lead to a K-Ras protein that is always active and can direct cells to grow and divide without control. Studies suggest that KRAS gene mutations are common in pancreatic, lung, and colorectal cancers. Mutations in the KRAS gene have also been found in other types of cancer.

other disorders - caused by mutations in the KRAS gene

KRAS mutations also cause a disorder whose major features overlap with those of Noonan syndrome and two other genetic conditions, cardiofaciocutaneous (CFC) syndrome and Costello syndrome. This condition has been described as the KRAS mutation-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 a single amino acid 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.

Where is the KRAS gene located?

Cytogenetic Location: 12p12.1

Molecular Location on chromosome 12: base pairs 25,249,446 to 25,295,120

The KRAS gene is located on the short (p) arm of chromosome 12 at position 12.1.

More precisely, the KRAS gene is located from base pair 25,249,446 to base pair 25,295,120 on chromosome 12.

What other names do people use for the KRAS gene or gene products?

• cellular c-Ki-ras2 proto-oncogene
• c-Kirsten-ras protein
• C-K-RAS
• c-K-ras2 protein
• c-K-ras protein
• KI-RAS
• Kirsten rat sarcoma-2 viral (v-Ki-ras2) oncogene homolog
• KRAS1
• KRAS2
• K-ras p21 protein
• NS3
• PR310 c-K-ras oncogene
• RASK2
• RASK_HUMAN
• transforming protein p21
• v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog

External Links

Where can I find additional information about KRAS?

You and your healthcare professional may find the following resources about KRAS helpful.

• Gene Reviews - Clinical summary (2 links)
• Gene Tests - DNA tests ordered by healthcare professionals (2 links)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

• PubMed - Recent literature
• OMIM - Genetic disorder catalog (4 links)
• Research Resources - Tools for researchers (6 links)

See How are genetic conditions and genes named? in the Handbook.

Where can I find general information about genes?

The Handbook provides basic information about genetics in clear language.

• What is DNA?
• What is a gene?
• How do genes direct the production of proteins?
• How can gene mutations affect health and development?

These links provide additional genetics resources that may be useful.

• Genetics education
• Human Genome Project
• Resources for Genetic Researchers

What glossary definitions help with understanding KRAS?

acids ; amino acid ; apoptosis ; atypical ; cancer ; cell ; cell division ; class ; colorectal ; critical region ; differentiation ; embryonic ; gene ; GTP ; homologs ; macrocephaly ; molecule ; mutation ; nucleus ; oncogene ; pancreatic ; phenotype ; protein ; proto-oncogene ; RAS ; RAS oncogene ; sarcoma ; short stature ; sign ; signal transduction ; somatic mutation ; stature ; symptom ; syndrome ; tissue ; transduction

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

See also Understanding Medical Terminology.

References

• Bell DA. Origins and molecular pathology of ovarian cancer. Mod Pathol. 2005 Feb;18 Suppl 2:S19-32. Review. PubMed citation
• Carta C, Pantaleoni F, Bocchinfuso G, Stella L, Vasta I, Sarkozy A, Digilio C, Palleschi A, Pizzuti A, Grammatico P, Zampino G, Dallapiccola B, Gelb BD, Tartaglia M. Germline Missense Mutations Affecting KRAS Isoform B Are Associated with a Severe Noonan Syndrome Phenotype. Am J Hum Genet. 2006 Jul;79(1):129-35. Epub 2006 May 1. PubMed citation
• Castagnola P, Giaretti W. Mutant KRAS, chromosomal instability and prognosis in colorectal cancer. Biochim Biophys Acta. 2005 Nov 25;1756(2):115-25. Epub 2005 Jul 13. Review. PubMed citation
• Colicelli J. Human RAS superfamily proteins and related GTPases. Sci STKE. 2004 Sep 7;2004(250):RE13. Review. PubMed citation
• Furukawa T, Sunamura M, Horii A. Molecular mechanisms of pancreatic carcinogenesis. Cancer Sci. 2006 Jan;97(1):1-7. Review. PubMed citation
• Gene Review: Cardiofaciocutaneous Syndrome
• Gene Review: Noonan syndrome
• Kranenburg O. The KRAS oncogene: past, present, and future. Biochim Biophys Acta. 2005 Nov 25;1756(2):81-2. Epub 2005 Oct 25. Review. No abstract available. PubMed citation
• Nava C, Hanna N, Michot C, Pereira S, Pouvreau N, Niihori T, Aoki Y, Matsubara Y, Arveiler B, Lacombe D, Pasmant E, Parfait B, Baumann C, Héron D, Sigaudy S, Toutain A, Rio M, Goldenberg A, Leheup B, Verloes A, Cavé H. Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype-phenotype relationships and overlap with Costello syndrome. J Med Genet. 2007 Dec;44(12):763-71. Epub 2007 Aug 17. PubMed citation
• Niihori T, Aoki Y, Narumi Y, Neri G, Cave H, Verloes A, Okamoto N, Hennekam RC, Gillessen-Kaesbach G, Wieczorek D, Kavamura MI, Kurosawa K, Ohashi H, Wilson L, Heron D, Bonneau D, Corona G, Kaname T, Naritomi K, Baumann C, Matsumoto N, Kato K, Kure S, Matsubara Y. Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Nat Genet. 2006 Mar;38(3):294-6. Epub 2006 Feb 12. PubMed citation
• Perez-Mancera PA, Tuveson DA. Physiological analysis of oncogenic k-ras. Methods Enzymol. 2005;407:676-90. PubMed citation
• Quezada E, Gripp KW. Costello syndrome and related disorders. Curr Opin Pediatr. 2007 Dec;19(6):636-44. PubMed citation
• Schubbert S, Zenker M, Rowe SL, Boll S, Klein C, Bollag G, van der Burgt I, Musante L, Kalscheuer V, Wehner LE, Nguyen H, West B, Zhang KY, Sistermans E, Rauch A, Niemeyer CM, Shannon K, Kratz CP. Germline KRAS mutations cause Noonan syndrome. Nat Genet. 2006 Mar;38(3):331-6. Epub 2006 Feb 12. Erratum in: Nat Genet. 2006 May;38(5):598. PubMed citation
• Zenker M, Lehmann K, Schulz AL, Barth H, Hansmann D, Koenig R, Korinthenberg R, Kreiss-Nachtsheim M, Meinecke P, Morlot S, Mundlos S, Quante AS, Raskin S, Schnabel D, Wehner LE, Kratz CP, Horn D, Kutsche K. Expansion of the genotypic and phenotypic spectrum in patients with KRAS germline mutations. J Med Genet. 2007 Feb;44(2):131-5. Epub 2006 Oct 20. PubMed citation