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Genetics Home Reference: your guide to understanding genetic conditions
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PTPN11

Reviewed April 2011

What is the official name of the PTPN11 gene?

The official name of this gene is “protein tyrosine phosphatase, non-receptor type 11.”

PTPN11 is the gene's official symbol. The PTPN11 gene is also known by other names, listed below.

What is the normal function of the PTPN11 gene?

The PTPN11 gene carries the instructions for making a protein called SHP-2. This protein helps control (regulate) the activation of the RAS/MAPK signaling pathway, which helps control several important cell functions. Specifically, it regulates the growth and division of cells (proliferation), the process by which cells mature to carry out specific functions (differentiation), cell movement (migration), and the self-destruction of cells (apoptosis). During embryonic development, the SHP-2 protein is critical in the development of the heart, blood cells, bones, and several other tissues.

The PTPN11 gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous.

Does the PTPN11 gene share characteristics with other genes?

The PTPN11 gene belongs to a family of genes called PTP (protein tyrosine phosphatases). It also belongs to a family of genes called SH2 domain containing (SH2 domain containing).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the PTPN11 gene related to health conditions?

multiple lentigines syndrome - caused by mutations in the PTPN11 gene

More than 10 mutations in the PTPN11 gene have been found to cause multiple lentigines syndrome (formerly called LEOPARD syndrome). This condition is characterized by multiple brown skin spots (lentigines), heart defects, short stature, genital abnormalities, hearing loss, and distinctive facial features. Most of these mutations change single protein building blocks (amino acids) in the SHP-2 protein. One common mutation that cause multiple lentigines syndrome replaces the amino acid tyrosine with the amino acid cysteine at position 279 (written Tyr279Cys or Y279C). Another common mutation replaces the amino acid threonine with the amino acid methionine at position 468 (written as Thr468Met or T468M) in the SHP-2 protein.

All known PTPN11 gene changes that cause multiple lentigines syndrome are believed to disrupt the protein's normal function. This decrease in SHP-2 protein function impairs the activation of the RAS/MAPK signaling pathway that controls cell functions such as growth and division. This misregulation can result in the various features of multiple lentigines syndrome.

Although the PTPN11 gene is an oncogene, a reduction in this protein's function does not seem to increase cancer risk in people with multiple lentigines syndrome.

Noonan syndrome - caused by mutations in the PTPN11 gene

More than 50 mutations causing Noonan syndrome have been identified in the PTPN11 gene. Most of these mutations replace single amino acids used to make the SHP-2 protein. The resulting proteins are either continuously active or have prolonged activation, rather than promptly switching on and off in response to other cellular proteins. This increase in protein activity disrupts the regulation of the RAS/MAPK signaling pathway that controls cell functions such as growth and division. This misregulation can result in the heart defects, growth problems, skeletal abnormalities, and other features of Noonan syndrome.

Rarely, a person with Noonan syndrome caused by PTPN11 gene mutations will also develop juvenile myelomonocytic leukemia, which is a type of blood cancer that typically affects children or adolescents.

cancers - increased risk from variations of the PTPN11 gene

Gene mutations can be acquired during a person's lifetime and are present only in certain cells. This type of mutation is called a somatic mutation, and it is not inherited. Somatic mutations in the PTPN11 gene can increase the risk of developing juvenile myelomonocytic leukemia. These mutations cause the SHP-2 protein to be continuously active. Overactivity of the SHP-2 protein disrupts the regulation of pathways that control the production of immature blood cells. As a result, certain white blood cells are overproduced, leading to this type of leukemia. Somatic mutations in the PTPN11 gene are found in about 35 percent of people with juvenile myelomonocytic leukemia.

Some studies indicate that somatic mutations in the PTPN11 gene are also associated with other blood disorders including chronic myelomonocytic leukemia, myelodysplastic syndrome, nonsyndromic acute myeloid leukemia, and acute lymphocytic leukemia. In rare cases, somatic PTPN11 gene mutations are found in cancers of the lung, colon, brain, thyroid, and in a type of skin cancer called melanoma.

other disorders - caused by mutations in the PTPN11 gene

Mutations in the PTPN11 gene can cause a condition called metachondromatosis. This condition is characterized by multiple benign (noncancerous) bone tumors called exostoses on the bones of the hands and feet. People with this condition also develop enchondromas, which are benign growths of cartilage. In people with metachondromatosis, the enchondromas form at the ends of the long bones or the sides of the hip bones. The growths characteristic of metachondromatosis typically develop during childhood and for reasons that are not understood, usually disappear over time.

Where is the PTPN11 gene located?

Cytogenetic Location: 12q24

Molecular Location on chromosome 12: base pairs 112,418,731 to 112,509,917

The PTPN11 gene is located on the long (q) arm of chromosome 12 at position 24.

The PTPN11 gene is located on the long (q) arm of chromosome 12 at position 24.

More precisely, the PTPN11 gene is located from base pair 112,418,731 to base pair 112,509,917 on chromosome 12.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about PTPN11?

You and your healthcare professional may find the following resources about PTPN11 helpful.

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

What other names do people use for the PTPN11 gene or gene products?

  • BPTP3
  • protein-tyrosine phosphatase 2C
  • protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1)
  • PTN11_HUMAN
  • PTP-1D
  • PTP2C
  • SHP2
  • SHP2 phosphatase
  • SH protein-tyrosine phosphatase
  • SH-PTP2
  • SH-PTP3

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding PTPN11?

acids ; acute ; acute lymphocytic leukemia ; acute myeloid leukemia ; amino acid ; apoptosis ; benign ; cancer ; cartilage ; cell ; chronic ; chronic myelomonocytic leukemia ; class ; colon ; cysteine ; differentiation ; domain ; embryonic ; exostoses ; gene ; homology ; inherited ; juvenile ; juvenile myelomonocytic leukemia ; leukemia ; melanoma ; methionine ; mutation ; myelodysplastic syndrome ; myeloid ; oncogene ; phosphatase ; proliferation ; protein ; RAS ; receptor ; short stature ; somatic mutation ; stature ; syndrome ; threonine ; thyroid ; tyrosine ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Aoki Y, Niihori T, Narumi Y, Kure S, Matsubara Y. The RAS/MAPK syndromes: novel roles of the RAS pathway in human genetic disorders. Hum Mutat. 2008 Aug;29(8):992-1006. doi: 10.1002/humu.20748. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18470943?dopt=Abstract)
  • Bentires-Alj M, Paez JG, David FS, Keilhack H, Halmos B, Naoki K, Maris JM, Richardson A, Bardelli A, Sugarbaker DJ, Richards WG, Du J, Girard L, Minna JD, Loh ML, Fisher DE, Velculescu VE, Vogelstein B, Meyerson M, Sellers WR, Neel BG. Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia. Cancer Res. 2004 Dec 15;64(24):8816-20. (http://www.ncbi.nlm.nih.gov/pubmed/15604238?dopt=Abstract)
  • Chan G, Kalaitzidis D, Neel BG. The tyrosine phosphatase Shp2 (PTPN11) in cancer. Cancer Metastasis Rev. 2008 Jun;27(2):179-92. doi: 10.1007/s10555-008-9126-y. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18286234?dopt=Abstract)
  • Digilio MC, Sarkozy A, de Zorzi A, Pacileo G, Limongelli G, Mingarelli R, Calabrò R, Marino B, Dallapiccola B. LEOPARD syndrome: clinical diagnosis in the first year of life. Am J Med Genet A. 2006 Apr 1;140(7):740-6. (http://www.ncbi.nlm.nih.gov/pubmed/16523510?dopt=Abstract)
  • Keren B, Hadchouel A, Saba S, Sznajer Y, Bonneau D, Leheup B, Boute O, Gaillard D, Lacombe D, Layet V, Marlin S, Mortier G, Toutain A, Beylot C, Baumann C, Verloes A, Cavé H; French Collaborative Noonan Study Group. PTPN11 mutations in patients with LEOPARD syndrome: a French multicentric experience. J Med Genet. 2004 Nov;41(11):e117. (http://www.ncbi.nlm.nih.gov/pubmed/15520399?dopt=Abstract)
  • Mohi MG, Neel BG. The role of Shp2 (PTPN11) in cancer. Curr Opin Genet Dev. 2007 Feb;17(1):23-30. Epub 2007 Jan 16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17227708?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5781)
  • OMIM: PROTEIN-TYROSINE PHOSPHATASE, NONRECEPTOR-TYPE, 11 (http://omim.org/entry/176876)
  • Romano AA, Allanson JE, Dahlgren J, Gelb BD, Hall B, Pierpont ME, Roberts AE, Robinson W, Takemoto CM, Noonan JA. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics. 2010 Oct;126(4):746-59. doi: 10.1542/peds.2009-3207. Epub 2010 Sep 27. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20876176?dopt=Abstract)
  • Sobreira NL, Cirulli ET, Avramopoulos D, Wohler E, Oswald GL, Stevens EL, Ge D, Shianna KV, Smith JP, Maia JM, Gumbs CE, Pevsner J, Thomas G, Valle D, Hoover-Fong JE, Goldstein DB. Whole-genome sequencing of a single proband together with linkage analysis identifies a Mendelian disease gene. PLoS Genet. 2010 Jun 17;6(6):e1000991. doi: 10.1371/journal.pgen.1000991. (http://www.ncbi.nlm.nih.gov/pubmed/20577567?dopt=Abstract)
  • Tartaglia M, Gelb BD. Germ-line and somatic PTPN11 mutations in human disease. Eur J Med Genet. 2005 Apr-Jun;48(2):81-96. Epub 2005 Apr 2. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16053901?dopt=Abstract)
  • Tartaglia M, Gelb BD. Noonan syndrome and related disorders: genetics and pathogenesis. Annu Rev Genomics Hum Genet. 2005;6:45-68. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16124853?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2011
Published: December 16, 2014