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    SLC29A3 Gene

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    Submitted by: Karina Chen
    (This entry belongs to Entry Collection "MedlinePlus ")

    Definition

    solute carrier family 29 member 3

    1. Normal Function

    The SLC29A3 gene provides instructions for making a protein called equilibrative nucleoside transporter 3 (ENT3). ENT3 belongs to a family of proteins that transport molecules called nucleosides in cells. With chemical modification, nucleosides become the building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP, which serve as energy sources in the cell. Molecules derived from nucleosides play an important role in many functions throughout the body.

    ENT3 is found in the membranes surrounding cell structures known as lysosomes and mitochondria. Lysosomes are compartments within the cell that use digestive enzymes to break down large molecules into smaller ones that can be reused by cells. Researchers believe that ENT3 transports nucleosides generated by the breakdown of DNA and RNA out of lysosomes into the cell so they can be reused.

    Mitochondria are structures within cells that convert the energy from food into a form that cells can use. While most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA (called mitochondrial DNA). Researchers believe that the ENT3 protein in mitochondrial membranes helps transport nucleosides into mitochondria; the nucleosides can then be used for the formation or repair of mitochondrial DNA and RNA, which are essential for proper functioning of the structures.

    2. Health Conditions Related to Genetic Changes

    2.1. Histiocytosis-lymphadenopathy plus syndrome

    Mutations in the SLC29A3 gene cause histiocytosis-lymphadenopathy plus syndrome, which is a group of conditions with overlapping signs and symptoms that affect many parts of the body. A feature common to the disorders in this spectrum is histiocytosis, which is the overgrowth of immune system cells called histiocytes. These cells abnormally accumulate in tissues, often in the lymph nodes of the neck. Buildup of these cells in the lymph nodes causes swelling of the lymph nodes (lymphadenopathy). Other features can include unusually dark (hyperpigmented) skin patches with excessive hair growth (hypertrichosis), diabetes, and hearing loss.

    The SLC29A3 gene mutations involved in this spectrum of disorders reduce or eliminate the activity of the ENT3 protein. Researchers are unsure how loss of ENT3 activity causes histiocytosis and other features of histiocytosis-lymphadenopathy plus syndrome. They speculate that the resulting impairment of nucleoside transport leads to a buildup of nucleosides in lysosomes and possibly in other cellular structures. The excess nucleosides may be damaging to cell function. A lack of ENT3 activity can also lead to a reduction in the amount of nucleosides in mitochondria. This nucleoside shortage could impair cellular energy production, which would impact many body systems. It is unclear how SLC29A3 gene mutations cause different patterns of signs and symptoms, even within the same family.

    3. Other Names for This Gene

    • ENT3
    • equilibrative nucleoside transporter 3
    • FLJ11160
    • HCLAP
    • HJCD
    • PHID
    • solute carrier family 29 (equilibrative nucleoside transporter), member 3
    • solute carrier family 29 (nucleoside transporters), member 3

    This entry is adapted from https://medlineplus.gov/genetics/gene/slc29a3

    References

    1. Baldwin SA, Yao SY, Hyde RJ, Ng AM, Foppolo S, Barnes K, Ritzel MW, Cass CE,Young JD. Functional characterization of novel human and mouse equilibrativenucleoside transporters (hENT3 and mENT3) located in intracellular membranes. JBiol Chem. 2005 Apr 22;280(16):15880-7.
    2. Govindarajan R, Leung GP, Zhou M, Tse CM, Wang J, Unadkat JD. Facilitatedmitochondrial import of antiviral and anticancer nucleoside drugs by humanequilibrative nucleoside transporter-3. Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G910-22. doi: 10.1152/ajpgi.90672.2008.
    3. Hsu CL, Lin W, Seshasayee D, Chen YH, Ding X, Lin Z, Suto E, Huang Z, Lee WP, Park H, Xu M, Sun M, Rangell L, Lutman JL, Ulufatu S, Stefanich E, Chalouni C,Sagolla M, Diehl L, Fielder P, Dean B, Balazs M, Martin F. Equilibrativenucleoside transporter 3 deficiency perturbs lysosome function and macrophagehomeostasis. Science. 2012 Jan 6;335(6064):89-92. doi: 10.1126/science.1213682.
    4. Kang N, Jun AH, Bhutia YD, Kannan N, Unadkat JD, Govindarajan R. Humanequilibrative nucleoside transporter-3 (hENT3) spectrum disorder mutations impairnucleoside transport, protein localization, and stability. J Biol Chem. 2010 Sep 3;285(36):28343-52. doi: 10.1074/jbc.M110.109199.
    5. Morgan NV, Morris MR, Cangul H, Gleeson D, Straatman-Iwanowska A, Davies N,Keenan S, Pasha S, Rahman F, Gentle D, Vreeswijk MP, Devilee P, Knowles MA,Ceylaner S, Trembath RC, Dalence C, Kismet E, Köseoğlu V, Rossbach HC, Gissen P, Tannahill D, Maher ER. Mutations in SLC29A3, encoding an equilibrative nucleosidetransporter ENT3, cause a familial histiocytosis syndrome (Faisalabadhistiocytosis) and familial Rosai-Dorfman disease. PLoS Genet. 2010 Feb5;6(2):e1000833. doi: 10.1371/journal.pgen.1000833.
    6. Young JD, Yao SY, Baldwin JM, Cass CE, Baldwin SA. The human concentrative andequilibrative nucleoside transporter families, SLC28 and SLC29. Mol Aspects Med. 2013 Apr-Jun;34(2-3):529-47. doi: 10.1016/j.mam.2012.05.007. Review.
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