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IGF2 gene
URL of this page: https://medlineplus.gov/genetics/gene/igf2/

IGF2 gene

insulin like growth factor 2

Normal Function

The IGF2 gene provides instructions for making a protein called insulin-like growth factor 2. This protein plays an essential role in growth and development before birth. Studies suggest that insulin-like growth factor 2 promotes the growth and division (proliferation) of cells in many different tissues. Although the IGF2 gene is highly active during fetal development, it is much less active after birth.

In most cases, people receive one copy of each gene from the egg cell and one copy from the sperm cell. Both copies are usually active, or "turned on," in cells. However, the activity of the IGF2 gene depends on whether the gene comes from the sperm cell or the egg cell. In most cases, only the IGF2 gene from the sperm cell is active. This parent-specific difference in gene activation is called genomic imprinting.

A nearby region of DNA regulates the genomic imprinting of the IGF2 gene and another gene, called H19, that is important for growth and development. This region is known as an imprinting center or imprinting control region. In a process known as methylation, small molecules called methyl groups are added to the imprinting center to regulate the activity of the IGF2 and H19 genes. Typically, only the copy of the IGF2 imprinting center that is derived from the sperm cell is methylated. 

Health Conditions Related to Genetic Changes

Beckwith-Wiedemann syndrome

Beckwith-Wiedemann syndrome, a growth disorder that affects many parts of the body, can result from changes that affect the IGF2 imprinting center. In some people with this condition, both copies of the IGF2 imprinting center are methylated. Because this region controls the genomic imprinting of the IGF2 and H19 genes, this abnormality disrupts the regulation of both genes. Specifically, this abnormal methylation of the IGF2 imprinting center leads to increased IGF2 gene activity and decreased H19 gene activity, which causes the overgrowth seen in people with Beckwith-Wiedemann syndrome.

In a few cases, Beckwith-Wiedemann syndrome has been caused by deletions of a small amount of DNA from the IGF2 imprinting center. These deletions impair the imprinting center’s ability to regulate the activity of the IGF2 and H19 genes.

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Prostate cancer

MedlinePlus Genetics provides information about Prostate cancer

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Silver-Russell syndrome

Changes in methylation are responsible for most cases of Silver-Russell syndrome, a disorder that is characterized by slow growth before and after birth. 

In people with Silver-Russell syndrome, the IGF2 imprinting center from the sperm cell often has fewer methyl groups than it should (hypomethylation). Hypomethylation of the imprinting center impairs its ability to regulate genes and leads to decreased IGF2 gene activity and increased H19 gene activity, which causes the slow growth seen in people with Silver-Russell syndrome. 

Rarely, variants (also called mutations) in the IGF2 gene cause Silver-Russell syndrome.

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Wilms tumor

Methylation changes have also been found in some cases of Wilms tumor, a rare form of kidney cancer that occurs almost exclusively in children.

In some people with Wilms tumor, both copies of the IGF2 imprinting center are methylated. This change leads to a decrease in H19 gene activity and an increase in IGF2 gene activity in kidney cells. This causes cells to produce more insulin-like growth factor 2 protein, which likely stimulates the growth of tumor cells in the kidney and prevents damaged cells from being destroyed. As this mechanism is similar to the one that causes Beckwith-Wiedemann syndrome, some children who have Beckwith-Wiedemann syndrome will also develop Wilms tumor. 

In most cases of Wilms tumor, abnormal methylation and subsequent changes in IGF2 and H19 gene activity are acquired during a person's lifetime (somatic) and are present only in the kidneys.

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Other cancers

Increased activity of the IGF2 gene has been associated with many types of cancer. Normally, the IGF2 gene undergoes genomic imprinting, and only the copy derived from the sperm cell is active. In some cancers, however, the IGF2 gene from both the egg cell and the sperm cell are active, increasing the amount of insulin-like growth factor 2 that cells can produce. This phenomenon, known as loss of imprinting (LOI), occurs during a person's lifetime in cells that ultimately give rise to cancer. An increased amount of insulin-like growth factor 2 may stimulate the growth of tumor cells and prevent damaged cells from being destroyed.

Loss of imprinting of the IGF2 gene has been identified in several types of cancer. In some cases, these cancers occur without any other related health problems, in other cases they occur in people with Beckwith-Wiedemann syndrome. These types of cancer include cancer of blood-forming cells (leukemia), a cancer of muscle tissue called rhabdomyosarcoma, a form of liver cancer called hepatoblastoma, and cancers of the breast, prostate, lung, and colon.

Other Names for This Gene

  • C11orf43
  • GRDF
  • IGF-2
  • IGF-II
  • insulin-like growth factor 2
  • insulin-like growth factor II
  • pp9974
  • somatomedin A

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

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  • Al-Hussain T, Ali A, Akhtar M. Wilms tumor: an update. Adv Anat Pathol. 2014 May;21(3):166-73. doi: 10.1097/PAP.0000000000000017. Citation on PubMed
  • Bergman D, Halje M, Nordin M, Engstrom W. Insulin-like growth factor 2 in development and disease: a mini-review. Gerontology. 2013;59(3):240-9. doi: 10.1159/000343995. Epub 2012 Dec 20. Citation on PubMed
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  • Eggermann T. Silver-Russell and Beckwith-Wiedemann syndromes: opposite (epi)mutations in 11p15 result in opposite clinical pictures. Horm Res. 2009 Apr;71 Suppl 2:30-5. doi: 10.1159/000192433. Epub 2009 Apr 29. Citation on PubMed
  • Kaneda A, Wang CJ, Cheong R, Timp W, Onyango P, Wen B, Iacobuzio-Donahue CA, Ohlsson R, Andraos R, Pearson MA, Sharov AA, Longo DL, Ko MS, Levchenko A, Feinberg AP. Enhanced sensitivity to IGF-II signaling links loss of imprinting of IGF2 to increased cell proliferation and tumor risk. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20926-31. doi: 10.1073/pnas.0710359105. Epub 2007 Dec 17. Citation on PubMed or Free article on PubMed Central
  • Livingstone C. IGF2 and cancer. Endocr Relat Cancer. 2013 Oct 24;20(6):R321-39. doi: 10.1530/ERC-13-0231. Print 2013 Dec. Citation on PubMed
  • MacFarland SP, Duffy KA, Bhatti TR, Bagatell R, Balamuth NJ, Brodeur GM, Ganguly A, Mattei PA, Surrey LF, Balis FM, Kalish JM. Diagnosis of Beckwith-Wiedemann syndrome in children presenting with Wilms tumor. Pediatr Blood Cancer. 2018 Oct;65(10):e27296. doi: 10.1002/pbc.27296. Epub 2018 Jun 22. Citation on PubMed or Free article on PubMed Central
  • Pickard A, McCance DJ. IGF-Binding Protein 2 - Oncogene or Tumor Suppressor? Front Endocrinol (Lausanne). 2015 Feb 27;6:25. doi: 10.3389/fendo.2015.00025. eCollection 2015. Citation on PubMed or Free article on PubMed Central
  • Sparago A, Cerrato F, Vernucci M, Ferrero GB, Silengo MC, Riccio A. Microdeletions in the human H19 DMR result in loss of IGF2 imprinting and Beckwith-Wiedemann syndrome. Nat Genet. 2004 Sep;36(9):958-60. doi: 10.1038/ng1410. Epub 2004 Aug 15. Citation on PubMed
  • Tian F, Yourek G, Shi X, Yang Y. The development of Wilms tumor: from WT1 and microRNA to animal models. Biochim Biophys Acta. 2014 Aug;1846(1):180-7. doi: 10.1016/j.bbcan.2014.07.003. Epub 2014 Jul 11. Citation on PubMed
  • Turner JT, Brzezinski J, Dome JS. Wilms Tumor Predisposition. 2003 Dec 19 [updated 2022 Mar 24]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1294/ Citation on PubMed

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