Normal Function
The MTTP gene provides instructions for making a protein called microsomal triglyceride transfer protein. This protein helps produce beta-lipoproteins, which are molecules that are made up of proteins (including one called apolipoprotein B), cholesterol, and particular types of fats called phospholipids and triglycerides.
Different types of beta-lipoproteins are made in the intestine and liver. In the intestine, beta-lipoproteins include chylomicrons, which are formed as food is digested after a meal to carry dietary fats and cholesterol from the intestine to the bloodstream. Chylomicrons are also necessary for the absorption of certain fat-soluble vitamins, such as vitamins E, A, and K. In the liver, beta-lipoproteins include low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL). These lipoproteins transport fats, cholesterol, and fat-soluble vitamins in the bloodstream to tissues throughout the body. Sufficient levels of fats, cholesterol, and vitamins are necessary for normal growth, development, and maintenance of the body's cells and tissues.
Health Conditions Related to Genetic Changes
Abetalipoproteinemia
More than 60 mutations in the MTTP gene have been found to cause abetalipoproteinemia. This condition impairs the normal absorption of fats and fat-soluble vitamins from the diet and primarily affects the gastrointestinal system, eyes, nervous system, and blood.
Most MTTP gene mutations lead to the production of microsomal triglyceride transfer protein with reduced or absent function, preventing the formation of beta-lipoproteins. One particular mutation is common in affected individuals of Ashkenazi (eastern and central European) Jewish descent; this mutation replaces the protein building block (amino acid) glycine with a premature stop signal at position 865 (written as Gly865Ter or G865X) in the instructions used to make the microsomal triglyceride transfer protein. As a result of this change, an abnormally small, nonfunctional version of the protein is made. All MTTP gene mutations that cause abetalipoproteinemia impair beta-lipoprotein formation and result in a severe shortage of chylomicrons, LDLs, and VLDLs. A lack of these lipoproteins prevents dietary fats and fat-soluble vitamins from being absorbed from the diet and transported through the bloodstream to the body's tissues. These nutritional deficiencies lead to health problems in people with abetalipoproteinemia.
More About This Health ConditionOther Names for This Gene
- ABL
- microsomal TG transfer protein
- microsomal triglyceride transfer protein (large polypeptide, 88kD)
- microsomal triglyceride transfer protein large subunit
- MTP
- MTP triglyceride carrier
- MTP_HUMAN
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Benayoun L, Granot E, Rizel L, Allon-Shalev S, Behar DM, Ben-Yosef T. Abetalipoproteinemia in Israel: evidence for a founder mutation in the Ashkenazi Jewish population and a contiguous gene deletion in an Arab patient. Mol Genet Metab. 2007 Apr;90(4):453-7. doi: 10.1016/j.ymgme.2006.12.010. Epub 2007 Feb 1. Citation on PubMed
- Gunduz M, Ozaydin E, Atar MB, Koc N, Kirsaclioglu C, Kose G, Cefalu AB, Averna M, Tarugi P. Microsomal triglyceride transfer protein gene mutations in Turkish children: A novel mutation and clinical follow up. Indian J Gastroenterol. 2016 May;35(3):236-41. doi: 10.1007/s12664-016-0654-z. Epub 2016 May 10. Citation on PubMed
- Hooper AJ, van Bockxmeer FM, Burnett JR. Monogenic hypocholesterolaemic lipid disorders and apolipoprotein B metabolism. Crit Rev Clin Lab Sci. 2005;42(5-6):515-45. doi: 10.1080/10408360500295113. Citation on PubMed
- Hussain MM, Iqbal J, Anwar K, Rava P, Dai K. Microsomal triglyceride transfer protein: a multifunctional protein. Front Biosci. 2003 May 1;8:s500-6. doi: 10.2741/1071. Citation on PubMed
- Swift LL, Kakkad B, Boone C, Jovanovska A, Jerome WG, Mohler PJ, Ong DE. Microsomal triglyceride transfer protein expression in adipocytes: a new component in fat metabolism. FEBS Lett. 2005 Jun 6;579(14):3183-9. doi: 10.1016/j.febslet.2005.05.009. Citation on PubMed
- Walsh MT, Di Leo E, Okur I, Tarugi P, Hussain MM. Structure-function analyses of microsomal triglyceride transfer protein missense mutations in abetalipoproteinemia and hypobetalipoproteinemia subjects. Biochim Biophys Acta. 2016 Nov;1861(11):1623-1633. doi: 10.1016/j.bbalip.2016.07.015. Epub 2016 Jul 31. Citation on PubMed
- Walsh MT, Hussain MM. Targeting microsomal triglyceride transfer protein and lipoprotein assembly to treat homozygous familial hypercholesterolemia. Crit Rev Clin Lab Sci. 2017 Jan;54(1):26-48. doi: 10.1080/10408363.2016.1221883. Epub 2016 Oct 1. Citation on PubMed
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