Defective SLC29A3 does not transport nucleosides from lysosomal lumen to cytosol

Stable Identifier
Reaction [transition]
Homo sapiens
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The human gene SLC29A3 encodes the equilibrative nucleoside transporter 3 (ENT3). It is abundant in many tissues, especially the placenta and is localized intracellularly on the lysosomal membrane. SLC29A3 mediates the reversible transport of nucleosides as well as anticancer and antiviral agents such as cladribine, cordycepin, tubercidin and AZT. Defects in SLC29A3 can cause histiocytosis-lymphadenopathy plus syndrome (HLAS; MIM:602782), an autosomal recessive disorder characterised by combined features from 2 or more of four histiocytic disorders. Mutations in SLC29A3 that can cause HLAS include G427S, L348Sfs*56, M116R, R363Q, R363W and R386Q (Mohlo-Pessach et al. 2008, Kang et al. 2010, Cliffe et al. 2009, Mohlo-Pessach et al. 2010, Farooq et al. 2012).
Literature References
PubMed ID Title Journal Year
19889517 The H syndrome: two novel mutations affecting the same amino acid residue of hENT3

Torrelo, A, Suarez, J, Doviner, V, Colmenero, I, Chiaverini, C, Perrin, C, Molho-Pessach, V, Tristan-Clavijo, E, Zlotogorski, A, Giuliano, F

J. Dermatol. Sci. 2010
19336477 SLC29A3 gene is mutated in pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome and interacts with the insulin signaling pathway

Kamsteeg, EJ, Kramer, JM, Lindeman, R, van Bokhoven, H, De Brouwer, AP, Hussain, K, Nibbeling, E, Schenck, A, Hennekam, RC, Deen, PM, Becknell, C, Robben, JH, Wong, M, Prendiville, J, James, C, de Jong, EK, Cliffe, ST, Padidela, R, Buckley, MF, Roscioli, T

Hum. Mol. Genet. 2009
22653152 Identification of two novel mutations in SLC29A3 encoding an equilibrative nucleoside transporter (hENT3) in two distinct Syrian families with H syndrome: expression studies of SLC29A3 (hENT3) in human skin

Farooq, M, Shimomura, Y, Fujikawa, H, Moustafa, RM, Fujimoto, A, Kurban, M, Kibbi, AG, Abbas, O

Dermatology (Basel) 2012
18940313 The H syndrome is caused by mutations in the nucleoside transporter hENT3

Molho-Pessach, V, Elpeleg, O, Lerer, I, Abeliovich, D, Broshtilova, V, Agha, Z, Abu Libdeh, A, Zlotogorski, A

Am J Hum Genet 2008
20595384 Human equilibrative nucleoside transporter-3 (hENT3) spectrum disorder mutations impair nucleoside transport, protein localization, and stability

Bhutia, YD, Kannan, N, Kang, N, Unadkat, JD, Govindarajan, R, Jun, AH

J. Biol. Chem. 2010
Catalyst Activity

nucleoside transmembrane transporter activity of SLC29A3 mutants [lysosomal membrane]

Normal reaction
Functional status

Loss of function of SLC29A3 mutants [lysosomal membrane]

Name Identifier Synonyms
histiocytosis DOID:3405 Hand Schuller Christian disease, chronic Histiocytosis X
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