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SLC29A3
solute carrier family 29 member 3
The SLC29A3 gene encodes the equilibrative nucleoside transporter 3 (ENT3) protein, vital for nucleoside transport within cells, particularly in lysosomes and mitochondria. SLC29A3 provides instructions for making the equilibrative nucleoside transporter 3 (ENT3) protein.
SLC29A3 is located on the long (q) arm of chromosome 10, at band 10q22.1. Arm ratio per GRCh38 - banding schematic.
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Overview
The SLC29A3 gene, also known as solute carrier family 29 member 3, plays a crucial role in cellular metabolism by encoding the equilibrative nucleoside transporter 3 (ENT3) protein. This protein is part of a family responsible for moving nucleosides across cell membranes. Nucleosides are essential precursors for DNA and RNA synthesis, as well as for energy-carrying molecules like ATP and GTP.
Disruptions in SLC29A3 function can lead to a spectrum of health conditions, collectively known as histiocytosis-lymphadenopathy plus syndrome, which affect various bodily systems.
What the gene does
The ENT3 protein, encoded by the SLC29A3 gene, functions as a transporter of nucleosides, which are molecules composed of a nucleobase and a sugar. These nucleosides are critical for the formation of DNA and RNA, as well as for cell energy. ENT3 is specifically located in the membranes of cellular organelles, namely lysosomes and mitochondria.
Within lysosomes, which are responsible for breaking down cellular waste, ENT3 is thought to transport nucleosides generated from the degradation of DNA and RNA out into the cell's cytoplasm for reuse. In mitochondria, the powerhouses of the cell that possess their own DNA, ENT3 is believed to facilitate the entry of nucleosides. This transport supports the formation and repair of mitochondrial DNA and RNA, which are essential for the proper functioning of these organelles.
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Chromosome location
The SLC29A3 gene is situated on chromosome 10, specifically at position 10q22.1. This location refers to the long (q) arm of chromosome 10, within region 22, band 1.
Protein structure
The SLC29A3 gene codes for a protein that is 475 amino acids long. Its structural features include a Disordered region spanning amino acids 1-24, and a Dileucine internalization motif found at amino acids 31-32. These specific regions may play roles in the protein's regulation and cellular targeting.
Key variants
Genetic variations within the SLC29A3 gene can influence the function of the equilibrative nucleoside transporter 3 (ENT3) protein. These variations, often referred to as pathogenic or likely pathogenic, can impact the protein's ability to transport nucleosides effectively. The specific consequences of a variant depend on its nature and location within the gene.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1087C>T | p.Arg363Trp | Pathogenic/Likely pathogenic | ★★☆☆ | SLC29A3-related disorder |
c.1228C>T | p.Gln410Ter | Pathogenic/Likely pathogenic | ★★☆☆ | H syndrome |
c.122del | p.Pro41fs | Pathogenic | ★★☆☆ | H syndrome |
c.1346C>G | p.Thr449Arg | Pathogenic/Likely pathogenic | ★★☆☆ | SLC29A3-related disorder |
c.243del | p.Lys81fs | Pathogenic | ★★☆☆ | SLC29A3-related disorder |
c.300+1G>A | - | Pathogenic | ★★☆☆ | H syndrome |
c.300+1G>C | - | Pathogenic | ★★☆☆ | SLC29A3-related disorder |
c.400C>T | p.Arg134Cys | Pathogenic/Likely pathogenic | ★★☆☆ | SLC29A3-related disorder |
c.479G>A | p.Trp160Ter | Pathogenic/Likely pathogenic | ★★☆☆ | H syndrome |
c.971C>T | p.Pro324Leu | Pathogenic/Likely pathogenic | ★★☆☆ | SLC29A3-related disorder |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the SLC29A3 gene are associated with histiocytosis-lymphadenopathy plus syndrome. This term encompasses a range of conditions that share common features, including the abnormal accumulation of immune system cells called histiocytes. These cells often build up in tissues, particularly in the lymph nodes.
No disease links recorded for this gene in our reference set.
UK clinical status
The SLC29A3 gene is included in several NHS Genomic Medicine Service clinical panels, indicating its recognised role in various conditions. These panels include Arthrogryposis, Autoinflammatory disorders, Diabetes with additional phenotypes suggestive of a monogenic aetiology, Familial diabetes, Foetal anomalies, Hypogonadotropic hypogonadism, Monogenic diabetes, Pigmentary skin disorders, Primary immunodeficiency or monogenic inflammatory bowel disease, and Skeletal dysplasia. It is also part of COVID-19 research panels.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the SLC29A3 gene?
The SLC29A3 gene provides instructions for making the equilibrative nucleoside transporter 3 (ENT3) protein. This protein is essential for transporting nucleosides, which are building blocks for DNA and RNA, within cellular structures like lysosomes and mitochondria.
What conditions are associated with changes in the SLC29A3 gene?
Variants in the SLC29A3 gene are linked to histiocytosis-lymphadenopathy plus syndrome. This condition involves the overgrowth and accumulation of immune cells called histiocytes in various tissues, especially lymph nodes.
Where is the SLC29A3 gene located?
The SLC29A3 gene is located on chromosome 10, specifically at position 10q22.1.
References
- Young JD, Yao SY, Baldwin JM. The human concentrative and equilibrative nucleoside transporter families, SLC28 and SLC29. Molecular aspects of medicine. 2013. PMID: 23506887
- Hsu CL, Lin W, Seshasayee D. Equilibrative nucleoside transporter 3 deficiency perturbs lysosome function and macrophage homeostasis. Science (New York, N.Y.). 2012. PMID: 22174130
- Morgan NV, Morris MR, Cangul H. Mutations in SLC29A3, encoding an equilibrative nucleoside transporter ENT3, cause a familial histiocytosis syndrome (Faisalabad histiocytosis) and familial Rosai-Dorfman disease. PLoS genetics. 2010. PMID: 20140240
- Kang N, Jun AH, Bhutia YD. Human equilibrative nucleoside transporter-3 (hENT3) spectrum disorder mutations impair nucleoside transport, protein localization, and stability. The Journal of biological chemistry. 2010. PMID: 20595384
- Govindarajan R, Leung GP, Zhou M. Facilitated mitochondrial import of antiviral and anticancer nucleoside drugs by human equilibrative nucleoside transporter-3. American journal of physiology. Gastrointestinal and liver physiology. 2009. PMID: 19164483
- Baldwin SA, Yao SY, Hyde RJ. Functional characterization of novel human and mouse equilibrative nucleoside transporters (hENT3 and mENT3) located in intracellular membranes. The Journal of biological chemistry. 2005. PMID: 15701636