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Genetics Home Reference: your guide to understanding genetic conditions
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DIRAS3

Reviewed August 2007

What is the official name of the DIRAS3 gene?

The official name of this gene is “DIRAS family, GTP-binding RAS-like 3.”

DIRAS3 is the gene's official symbol. The DIRAS3 gene is also known by other names, listed below.

What is the normal function of the DIRAS3 gene?

The DIRAS3 gene is a member of a large family of genes known as Ras genes. Genes in this family provide instructions for making proteins that control cell growth and maturation. The DIRAS3 protein differs from other proteins in the Ras family in that it suppresses the growth of cells, whereas other Ras family proteins encourage cell growth. Genes that suppress cell growth and division are known as tumor suppressor genes. The proteins made from these genes keep cells from growing and dividing too fast or in an uncontrolled way.

The DIRAS3 gene provides instructions for making a protein that is located in the fluid within cells (the cytoplasm) and in the cell membrane of normal cells in the breasts and ovaries. It interacts with several other proteins to help control cell growth and division.

In each cell, one copy of the DIRAS3 gene—the copy inherited from a person's mother (the maternal copy)—is nonfunctional throughout life. Only the copy inherited from a person's father (the paternal copy) is active. When the copy of gene inherited from one specific parent is inactivated, this phenomenon is known as genomic imprinting.

How are changes in the DIRAS3 gene related to health conditions?

breast cancer - associated with the DIRAS3 gene

Research has shown that the tumor suppressor gene DIRAS3 is often downregulated in breast cancer cells, which means its activity is drastically reduced. In some cases, the gene is totally inactivated or lost. Because of genomic imprinting, cells normally have only one working copy of the DIRAS3 gene, the paternal copy. If this copy of the gene is inactivated or lost, cells produce little or no functional DIRAS3 protein. Without enough of this protein, cells can grow and divide too fast and in an uncontrolled manner. This abnormal cell division likely contributes to the growth and progression of cancerous tumors.

other cancers - associated with the DIRAS3 gene

Loss or inactivation of the paternal copy of the DIRAS3 gene is also associated with ovarian cancer. As in breast cancer cells, a shortage of the DIRAS3 protein may allow certain cells in the ovaries to grow and divide too fast and in an uncontrolled manner. This abnormal cell division is associated with the growth and progression of cancerous tumors. Downregulation of the DIRAS3 gene has also been reported in certain forms of uterine cancer, pancreatic cancer, lung cancer, and a cancer of the thyroid gland called follicular thyroid carcinoma.

Where is the DIRAS3 gene located?

Cytogenetic Location: 1p31

Molecular Location on chromosome 1: base pairs 68,045,961 to 68,050,996

The DIRAS3 gene is located on the short (p) arm of chromosome 1 at position 31.

The DIRAS3 gene is located on the short (p) arm of chromosome 1 at position 31.

More precisely, the DIRAS3 gene is located from base pair 68,045,961 to base pair 68,050,996 on chromosome 1.

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 DIRAS3?

You and your healthcare professional may find the following resources about DIRAS3 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 DIRAS3 gene or gene products?

  • ARHI
  • DIRA3_HUMAN
  • NOEY2
  • ras homolog gene family, member I
  • ras homolog I
  • Ras-related GTP-binding protein, member I
  • Rho-related GTP-binding protein RhoI

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 DIRAS3?

cancer ; carcinoma ; cell ; cell division ; cell membrane ; cytoplasm ; gene ; GTP ; heterozygosity ; imprinting ; inherited ; loss of heterozygosity ; maternal ; ovarian ; pancreatic ; progression ; protein ; RAS ; thyroid ; tumor ; tumor suppressor gene

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

References

  • Dalai I, Missiaglia E, Barbi S, Butturini G, Doglioni C, Falconi M, Scarpa A. Low expression of ARHI is associated with shorter progression-free survival in pancreatic endocrine tumors. Neoplasia. 2007 Mar;9(3):181-3. (http://www.ncbi.nlm.nih.gov/pubmed/17401457?dopt=Abstract)
  • Hisatomi H, Nagao K, Wakita K, Kohno N. ARHI/NOEY2 inactivation may be important in breast tumor pathogenesis. Oncology. 2002;62(2):136-40. (http://www.ncbi.nlm.nih.gov/pubmed/11914599?dopt=Abstract)
  • Luo RZ, Fang X, Marquez R, Liu SY, Mills GB, Liao WS, Yu Y, Bast RC. ARHI is a Ras-related small G-protein with a novel N-terminal extension that inhibits growth of ovarian and breast cancers. Oncogene. 2003 May 15;22(19):2897-909. (http://www.ncbi.nlm.nih.gov/pubmed/12771940?dopt=Abstract)
  • Luo RZ, Peng H, Xu F, Bao J, Pang Y, Pershad R, Issa JP, Liao WS, Bast RC Jr, Yu Y. Genomic structure and promoter characterization of an imprinted tumor suppressor gene ARHI. Biochim Biophys Acta. 2001 Jun 28;1519(3):216-22. (http://www.ncbi.nlm.nih.gov/pubmed/11418188?dopt=Abstract)
  • Lu Z, Luo RZ, Peng H, Rosen DG, Atkinson EN, Warneke C, Huang M, Nishmoto A, Liu J, Liao WS, Yu Y, Bast RC Jr. Transcriptional and posttranscriptional down-regulation of the imprinted tumor suppressor gene ARHI (DRAS3) in ovarian cancer. Clin Cancer Res. 2006 Apr 15;12(8):2404-13. (http://www.ncbi.nlm.nih.gov/pubmed/16638845?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/9077)
  • Nishimoto A, Yu Y, Lu Z, Mao X, Ren Z, Watowich SS, Mills GB, Liao WS, Chen X, Bast RC Jr, Luo RZ. A Ras homologue member I directly inhibits signal transducers and activators of transcription 3 translocation and activity in human breast and ovarian cancer cells. Cancer Res. 2005 Aug 1;65(15):6701-10. (http://www.ncbi.nlm.nih.gov/pubmed/16061651?dopt=Abstract)
  • Wang L, Hoque A, Luo RZ, Yuan J, Lu Z, Nishimoto A, Liu J, Sahin AA, Lippman SM, Bast RC Jr, Yu Y. Loss of the expression of the tumor suppressor gene ARHI is associated with progression of breast cancer. Clin Cancer Res. 2003 Sep 1;9(10 Pt 1):3660-6. (http://www.ncbi.nlm.nih.gov/pubmed/14506155?dopt=Abstract)
  • Weber F, Aldred MA, Morrison CD, Plass C, Frilling A, Broelsch CE, Waite KA, Eng C. Silencing of the maternally imprinted tumor suppressor ARHI contributes to follicular thyroid carcinogenesis. J Clin Endocrinol Metab. 2005 Feb;90(2):1149-55. Epub 2004 Nov 16. (http://www.ncbi.nlm.nih.gov/pubmed/15546898?dopt=Abstract)
  • Yuan J, Luo RZ, Fujii S, Wang L, Hu W, Andreeff M, Pan Y, Kadota M, Oshimura M, Sahin AA, Issa JP, Bast RC Jr, Yu Y. Aberrant methylation and silencing of ARHI, an imprinted tumor suppressor gene in which the function is lost in breast cancers. Cancer Res. 2003 Jul 15;63(14):4174-80. (http://www.ncbi.nlm.nih.gov/pubmed/12874023?dopt=Abstract)
  • Yu Y, Fujii S, Yuan J, Luo RZ, Wang L, Bao J, Kadota M, Oshimura M, Dent SR, Issa JP, Bast RC Jr. Epigenetic regulation of ARHI in breast and ovarian cancer cells. Ann N Y Acad Sci. 2003 Mar;983:268-77. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12724231?dopt=Abstract)
  • Yu Y, Luo R, Lu Z, Wei Feng W, Badgwell D, Issa JP, Rosen DG, Liu J, Bast RC Jr. Biochemistry and biology of ARHI (DIRAS3), an imprinted tumor suppressor gene whose expression is lost in ovarian and breast cancers. Methods Enzymol. 2006;407:455-68. (http://www.ncbi.nlm.nih.gov/pubmed/16757345?dopt=Abstract)
  • Yu Y, Xu F, Peng H, Fang X, Zhao S, Li Y, Cuevas B, Kuo WL, Gray JW, Siciliano M, Mills GB, Bast RC Jr. NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas. Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):214-9. (http://www.ncbi.nlm.nih.gov/pubmed/9874798?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: August 2007
Published: July 21, 2014