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Normal Function
The TTPA gene provides instructions for making the α-tocopherol transfer protein (αTTP), which is found in the liver and brain. This protein controls the distribution of vitamin E obtained from the diet (also called α-tocopherol) to cells and tissues throughout the body. Vitamin E is an antioxidant that protects cells in the body from the damaging effects of unstable molecules called free radicals. Normally, vitamin E derived from food is absorbed in the intestine and then transported into the liver on molecules called chylomicrons.
After a meal, chylomicrons are formed to transport fat-soluble vitamins (such as vitamin E), dietary fats, and cholesterol from the intestine to the liver. Once in the liver, αTTP transfers vitamin E from chylomicrons to very low-density lipoproteins (VLDLs), which carry fat, fat-soluble vitamins, and cholesterol from the liver to other tissues throughout the body. The VLDLs are then released into the bloodstream so the accompanying vitamin E can be used in the body. The αTTP protein is also thought to transport vitamin E to nerve cells (neurons) in the brain.
Health Conditions Related to Genetic Changes
Ataxia with vitamin E deficiency
More than 20 mutations in the TTPA gene have been found to cause ataxia with vitamin E deficiency. This condition is characterized by the development of neurological problems including difficulty coordinating movements (ataxia) due to a buildup of harmful molecules called free radicals. Some of these mutations cause no functional protein to be made, while others change a single protein building block (amino acid) in the αTTP protein, reducing its function. As a result, the body cannot retain or use dietary vitamin E, which leads to reduced levels of this vitamin in the blood and the accumulation of free radicals.
One TTPA gene mutation that is found in the Japanese population changes the amino acid histidine to the amino acid glutamine at position 101 in the αTTP protein (written as His101Glu or H101Q). This mutation is associated with the development of an eye disorder called retinitis pigmentosa that causes vision loss in people with ataxia with vitamin E deficiency.
Mutations in the TTPA gene that cause no functional αTTP protein to be made are associated with a severe form of ataxia that begins at a young age. Mutations that reduce but do not eliminate the protein's function are associated with milder ataxia that occurs at a later age and progresses more slowly.
More About This Health ConditionOther Names for This Gene
- alpha-tocopherol transfer protein
- alphaTTP
- ataxia (Friedreich-like) with vitamin E deficiency
- ATTP
- AVED
- tocopherol (alpha) transfer protein
- TTP1
- TTPA_HUMAN
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Mariotti C, Gellera C, Rimoldi M, Mineri R, Uziel G, Zorzi G, Pareyson D, Piccolo G, Gambi D, Piacentini S, Squitieri F, Capra R, Castellotti B, Di Donato S. Ataxia with isolated vitamin E deficiency: neurological phenotype, clinical follow-up and novel mutations in TTPA gene in Italian families. Neurol Sci. 2004 Jul;25(3):130-7. doi: 10.1007/s10072-004-0246-z. Citation on PubMed
- Meier R, Tomizaki T, Schulze-Briese C, Baumann U, Stocker A. The molecular basis of vitamin E retention: structure of human alpha-tocopherol transfer protein. J Mol Biol. 2003 Aug 15;331(3):725-34. doi: 10.1016/s0022-2836(03)00724-1. Citation on PubMed
- Morley S, Panagabko C, Shineman D, Mani B, Stocker A, Atkinson J, Manor D. Molecular determinants of heritable vitamin E deficiency. Biochemistry. 2004 Apr 13;43(14):4143-9. doi: 10.1021/bi0363073. Citation on PubMed
- Pang J, Kiyosawa M, Seko Y, Yokota T, Harino S, Suzuki J. Clinicopathological report of retinitis pigmentosa with vitamin E deficiency caused by mutation of the alpha-tocopherol transfer protein gene. Jpn J Ophthalmol. 2001 Nov-Dec;45(6):672-6. doi: 10.1016/s0021-5155(01)00425-7. Citation on PubMed
- Qian J, Atkinson J, Manor D. Biochemical consequences of heritable mutations in the alpha-tocopherol transfer protein. Biochemistry. 2006 Jul 11;45(27):8236-42. doi: 10.1021/bi060522c. Citation on PubMed
- Yokota T, Shiojiri T, Gotoda T, Arita M, Arai H, Ohga T, Kanda T, Suzuki J, Imai T, Matsumoto H, Harino S, Kiyosawa M, Mizusawa H, Inoue K. Friedreich-like ataxia with retinitis pigmentosa caused by the His101Gln mutation of the alpha-tocopherol transfer protein gene. Ann Neurol. 1997 Jun;41(6):826-32. doi: 10.1002/ana.410410621. Citation on PubMed
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