URL of this page: https://medlineplus.gov/genetics/gene/itm2b/

ITM2B gene

integral membrane protein 2B

Normal Function

The ITM2B gene provides instructions for producing a protein called the integral membrane protein 2B (ITM2B), which is found in all tissues. The function of the ITM2B protein is unclear. It is thought to play a role in triggering the self-destruction of cells (apoptosis) and in keeping cells from growing and dividing too fast or in an uncontrolled way (suppressing tumor formation). Additionally, the ITM2B protein may be involved in processing the amyloid precursor protein, which is produced by the APP gene. Not much is known about amyloid precursor protein function, but it is thought to be involved in nerve cell function in the brain in early development. Processing this protein creates different forms of the protein that can carry out various functions. Research suggests that the ITM2B protein is also involved in preventing (inhibiting) a form of the amyloid precursor protein from accumulating in the body's cells and tissues.

Health Conditions Related to Genetic Changes

Hereditary cerebral amyloid angiopathy

Two variants (also called mutations) in the ITM2B gene have been found to cause a condition called hereditary cerebral amyloid angiopathy. When this condition is caused by variants in the ITM2B gene, it is characterized by movement problems and a decline in intellectual function (dementia). ITM2B gene variants cause two forms of the condition called familial British dementia and familial Danish dementia, named for the regions where the conditions were first diagnosed. The ITM2B gene variant that causes the British type results in the production of a protein that is longer than normal. The ITM2B protein normally has a stop signal that indicates where to stop the protein sequence so that all the ITM2B proteins that are made are the same. The variant that causes the British type changes the stop signal so that more length is added to the protein. This variant is written as Ter267Arg or X267R. The variant that causes the Danish type is similar, but instead of changing the stop signal, extra pieces of DNA are added to the gene, which means that the protein is longer. This variant is written as 795-796insTTTAATTTGT.

The ITM2B gene variants that cause the British type or the Danish type dementia produce elongated precursor proteins, which lead to proteins variants known as ABri or ADan respectively. These proteins have altered 3-dimensional shapes that make them prone to cluster together (aggregate). These aggregated proteins form clumps called amyloid deposits, which accumulate in specific areas of the brain and in its blood vessels. The amyloid deposits trigger activation of the complement system, which is a group of immune system proteins that work together to destroy pathogens, trigger inflammation, and remove debris from cells and tissues. Other immune system reactions are also activated, which all attack the area surrounding the amyloid deposit. The complement system and other reactions lead to cell death and tissue damage in various parts of the brain. These abnormalities underlie the signs and symptoms of the familial British dementia and familial Danish dementia types of hereditary cerebral amyloid angiopathy.

More About This Health Condition

Other Names for This Gene

  • ABRI
  • BRI2
  • BRICD2B
  • E25B
  • ITM2B_HUMAN

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

  • Fotinopoulou A, Tsachaki M, Vlavaki M, Poulopoulos A, Rostagno A, Frangione B, Ghiso J, Efthimiopoulos S. BRI2 interacts with amyloid precursor protein (APP) and regulates amyloid beta (Abeta) production. J Biol Chem. 2005 Sep 2;280(35):30768-72. Epub 2005 Jul 18. Citation on PubMed
  • Ghiso J, Rostagno A, Tomidokoro Y, Lashley T, Bojsen-Møller M, Braendgaard H, Plant G, Holton J, Lal R, Revesz T, Frangione B. Genetic alterations of the BRI2 gene: familial British and Danish dementias. Brain Pathol. 2006 Jan;16(1):71-9. Citation on PubMed
  • Kim J, Miller VM, Levites Y, West KJ, Zwizinski CW, Moore BD, Troendle FJ, Bann M, Verbeeck C, Price RW, Smithson L, Sonoda L, Wagg K, Rangachari V, Zou F, Younkin SG, Graff-Radford N, Dickson D, Rosenberry T, Golde TE. BRI2 (ITM2b) inhibits Abeta deposition in vivo. J Neurosci. 2008 Jun 4;28(23):6030-6. doi: 10.1523/JNEUROSCI.0891-08.2008. Citation on PubMed or Free article on PubMed Central
  • Revesz T, Ghiso J, Lashley T, Plant G, Rostagno A, Frangione B, Holton JL. Cerebral amyloid angiopathies: a pathologic, biochemical, and genetic view. J Neuropathol Exp Neurol. 2003 Sep;62(9):885-98. Review. Citation on PubMed
  • Revesz T, Holton JL, Lashley T, Plant G, Frangione B, Rostagno A, Ghiso J. Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies. Acta Neuropathol. 2009 Jul;118(1):115-30. doi: 10.1007/s00401-009-0501-8. Epub 2009 Feb 19. Review. Erratum in: Acta Neuropathol. 2009 Aug;118(2):321. Citation on PubMed or Free article on PubMed Central
  • Rostagno A, Revesz T, Lashley T, Tomidokoro Y, Magnotti L, Braendgaard H, Plant G, Bojsen-Møller M, Holton J, Frangione B, Ghiso J. Complement activation in chromosome 13 dementias. Similarities with Alzheimer's disease. J Biol Chem. 2002 Dec 20;277(51):49782-90. Epub 2002 Oct 17. Citation on PubMed
  • Vidal R, Frangione B, Rostagno A, Mead S, Révész T, Plant G, Ghiso J. A stop-codon mutation in the BRI gene associated with familial British dementia. Nature. 1999 Jun 24;399(6738):776-81. Citation on PubMed
  • Vidal R, Revesz T, Rostagno A, Kim E, Holton JL, Bek T, Bojsen-Møller M, Braendgaard H, Plant G, Ghiso J, Frangione B. A decamer duplication in the 3' region of the BRI gene originates an amyloid peptide that is associated with dementia in a Danish kindred. Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4920-5. Citation on PubMed

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