Alternative titles; symbols
HGNC Approved Gene Symbol: SLC6A6
Cytogenetic location: 3p25.1 Genomic coordinates (GRCh38): 3:14,402,576-14,489,349 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 3p25.1 | Hypotaurinemic retinal degeneration and cardiomyopathy | 145350 | Autosomal recessive | 3 |
Taurine (2-aminoethanesulfonic acid) is a major intracellular amino acid in mammals. It is involved in a number of important physiologic processes, including bile acid conjugation in hepatocytes, modulation of calcium flux and neural excitability, osmoregulation, detoxification, and membrane stabilization. The cells of most organisms respond to hypertonicity by the intracellular accumulation of high concentrations of small organic solutes (osmolytes) that, in contrast to high concentrations of electrolytes, do not perturb the function of macromolecules. The renal medulla is normally the only tissue in mammals that undergoes wide shifts in tonicity. Its hypertonicity when the kidney is excreting a concentrated urine is fundamental to water conservation. The taurine content of the renal medulla of rats infused with 5% NaCl is higher than that in controls, suggesting that taurine behaves as an osmolyte in the renal medulla. Indeed, taurine functions as an osmolyte in Madin-Darby canine kidney (MDCK) cells. When MDCK cells cultured in isotonic medium are switched to hypertonic medium, their content of taurine doubles through the taking up of taurine from the medium. Taurine transport in these cells is dependent on sodium and chloride ions and is localized primarily in the basolateral plasma membrane (summary by Uchida et al., 1992).
Uchida et al. (1992) cloned the cDNA for the taurine transporter in MDCK cells. The sequence of the cDNA indicated that the taurine transporter has considerable amino acid sequence similarity to previously cloned Na(+)- and Cl(-)-dependent transporters. Northern hybridization indicated that the quantity of mRNA for the taurine transporter in MDCK cells is regulated by hypertonicity. Furthermore, the Northern hybridizations indicated that the taurine transporter is present also in ileal mucosa, brain, liver, and heart.
From a human placenta cDNA library, Ramamoorthy et al. (1994) isolated a cDNA clone highly related to the rat brain taurine transporter. The clone included a coding region of 1,863 bp (including the termination codon). The nucleotide sequence of the coding region predicted a 620-amino acid protein with a calculated molecular mass of 69,853. Northern blot analysis demonstrated that the principal transcript, 6.9 kb in size, is expressed abundantly in placenta and skeletal muscle, at intermediate levels in heart, brain, lung, kidney, and pancreas, and at low levels in liver. Cultured human cell lines derived from placenta, intestine, cervix (HeLa), and retinal pigment epithelium, which are known to possess Na(+)- and Cl(-)-coupled taurine transport activity, also contained the 6.9-kb transcript.
By somatic cell hybrid and isotopic in situ hybridization studies, Ramamoorthy et al. (1994) assigned the taurine transporter gene to 3p26-p24. Using a panel of somatic cell hybrids containing defined deletions of chromosome 3, Patel et al. (1995) mapped the TAUT gene to 3p25-p21. By genetic linkage mapping, they assigned the mouse homolog to chromosome 6. Taken in conjunction with the earlier mapping of the gene in the human, one can arrive at a consensus mapping of 3p25-p24.
Ramamoorthy et al. (1994) showed that transfection of this cDNA into HeLa cells resulted in a marked elevation of taurine transport activity. The activity of the cDNA-induced transporter was dependent on the presence of Na(+) as well as Cl(-). The transporter was specific for taurine and other beta-amino acids, including beta-alanine, and exhibited high affinity for taurine (Michaelis-Menten constant, approximately 6 microM).
In 2 Pakistani sibs with hypotaurinemic retinal degeneration and cardiomyopathy (HTRDC; 145350), Ansar et al. (2020) identified a homozygous missense mutation in the SLC6A6 gene (G399V; 186854.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family.
In 2 Turkish sibs with HTRDC, Preising et al. (2019) identified a homozygous missense mutation (A78E; 186854.0002) in the SLC6A6 gene. The mutation, which was found by linkage analysis followed by targeted next-generation sequencing, segregated with the disorder in the family.
Ito et al. (2010) described cardiac and skeletal muscle findings in an Slc6a6 deficient mouse, TauTKO. The mice developed dilated cardiomyopathy at 9 months of age, and examination of heart tissue showed ventricular remodeling with significant ultrastructural damage of myofilaments and mitochondria. The knockout mice also had loss of body weight, reduced exercise capacity, undetectable taurine in heart tissue, and reduced taurine in skeletal muscle.
In a review of biologic properties of taurine, Ripps and Shen (2012) described eye findings in a mouse knockout of Slc6a6. The knockout mice exhibited ganglion cell loss and degenerative changes in the retina, leading Ripps and Shen (2012) to conclude that taurine has a neuroprotective role in ganglion cells and in the distal retina.
In 2 Pakistani sibs, born to consanguineous parents, with hypotaurinemic retinal degeneration and cardiomyopathy (HTRDC; 145350), Ansar et al. (2020) identified homozygosity for a c.1196G-T transversion (c.1196G-T, NM_003043.5) in the SLC6A6 gene, resulting in a gly399-to-val (G399V) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Molecular modeling of the mutant SLC6A6 protein predicted that the G399V mutation was important for ligand recognition and transport. Transient transfection of HEK293 cells with SLC6A6 containing the G399V mutation resulted in reduced taurine transport capacity.
In 4- and 11-year-old Turkish sibs, born to consanguineous parents, with hypotaurinemic retinal degeneration and cardiomyopathy (HTRDC; 145350), Preising et al. (2019) identified homozygosity for a c.233C-A transversion (c.233C-A, NM_003043.5) in the SLC6A6 gene, resulting in an ala78-to-glu (A78E) substitution at a conserved residue. The mutation, which was found by genomewide genotyping and linkage analysis in the sibs and their parents, followed by targeted next-generation sequencing in one of the sibs. The mutation was confirmed by Sanger sequencing, and the parents were confirmed to be mutation carriers. Taurine uptake was reduced in peripheral blood mononuclear cells from the patients, and taurine levels were reduced in patient plasma, skeletal muscle, and brain.
Ansar, M., Ranza, E., Shetty M., Paracha, S. A., Azam, M., Kern, I., Iwaszkiewicz, J., Farooq, O., Pournaras, C. J., Malcles, A., Kecik, M., Rivolta, C., and 11 others. Taurine treatment of retinal degeneration and cardiomyopathy in a consanguineous family with SLC6A6 taurine transporter deficiency. Hum. Molec. Genet. 29: 618-628, 2020. [PubMed: 31903486] [Full Text: https://doi.org/10.1093/hmg/ddz303]
Ito, T., Oishi, S., Takai, M., Kimura, Y., Uozumi, Y., Fujio, Y., Schaffer, S. W., Azuma, J. Cardiac and skeletal muscle abnormality in taurine transporter-knockout mice. J. Biomed. Sci. 17 (Suppl. 1): S20, 2010. [PubMed: 20804595] [Full Text: https://doi.org/10.1186/1423-0127-17-S1-S20]
Patel, A., Rochelle, J. M., Jones, J. M., Sumegi, J., Uhl, G. R., Seldin, M. F., Meisler, M. H., Gregor, P. Mapping of the taurine transporter gene to mouse chromosome 6 and to the short arm of human chromosome 3. Genomics 25: 314-317, 1995. [PubMed: 7774940] [Full Text: https://doi.org/10.1016/0888-7543(95)80146-d]
Preising, M. N., Gorg, B., Friedburg, C., Qvartskhava, N., Budde, B. S., Bonus, M., Toliat, M. R., Pfleger, C., Altmuller, J., Herebian, D., Beyer, M., Zollner, H. J., and 11 others. Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration. FASEB J. 33: 11507-11527, 2019. [PubMed: 31345061] [Full Text: https://doi.org/10.1096/fj.201900914RR]
Ramamoorthy, S., Leibach, F. H., Mahesh, V. B., Han, H., Yang-Feng, T., Blakely, R. D., Ganapathy, V. Functional characterization and chromosomal localization of a cloned taurine transporter from human placenta. Biochem. J. 300: 893-900, 1994. [PubMed: 8010975] [Full Text: https://doi.org/10.1042/bj3000893]
Ripps, H., Shen, W. Review: Taurine: a 'very essential' amino acid. Molec. Vision 18: 2673-2686, 2012. [PubMed: 23170060]
Uchida, S., Kwon, H. M., Yamauchi, A., Preston, A. S., Marumo, F., Handler, J. S. Molecular cloning of the cDNA for an MDCK cell Na(+)- and Cl(-)-dependent taurine transporter that is regulated by hypertonicity. Proc. Nat. Acad. Sci. 89: 8230-8234, 1992. Note: Erratum: Proc. Nat. Acad. Sci. 24: 7424 only, 1993. [PubMed: 1518851] [Full Text: https://doi.org/10.1073/pnas.89.17.8230]