The human SLC19A3 gene spans 32.9 kb of genomic DNA and is comprised of 8 exons. Orthologs of SLC19A3 are found in 47 different organisms.

5 transcript variants for SLC19A3 are described from the NCBI Homo sapiens Annotation Release 106. NM_025243 (GenBank accession #) represents the main transcript (6 exons, 3775 bp) that encodes a peptide of 496 amino acids (Thiamine transporter-2, THTR-2). The remaining 4 variants were identified from computational annotation and include XM_005246871 (3836 bp, 6 exons, 546 aa), XM_005246874 (3288 bp, 7 exons, 492 aa), XM_006712779 (3210 bp, 6 exons, 501 aa) and XM_005246875 (1257 bp, 4 exons, 383 aa).
The stimulating protein-1 (SP1)/ guanosine cytidine (GC) box has been identified in the thiamine-responsive region of SLC19A3 promoter, and SP1 transcriptional factor was reported for regulating THTR-2 expression in response to extracellular thiamine level (Nabokina et al., 2013).

Two SLC19A3-related pseudogenes have been reported, namely LOC100130121 locating at chromosome 7p11, and LOC100420667 locating at chromosome 2q37.

The protein product of SLC19A3 gene is often referred as thiamine transporter-2 (THTR-2).

A thiamine transporter protein of 496 amino acid residues, 56 kDa, containing 12 transmembrane domains, and cytosolic N- and C-terminals (Eudy et al., 2000).

SLC19A3 expression has been widely detetced in human tissues including brain, heart, gastrointestinal tract, lung, pancreas, muscle, ovary, testis, adrenal gland, with the highest levels observed in placenta, liver and kidney (Eudy et al., 2000). A more restricted pattern of SLC19A3 expression was found in mouse tissues, including only brain, heart, lung, kidney and small intestine.

Plasma membrane. In polarized intestinal epithelial cells, THTR-2 are restrictedly localized at the apical membrane domain (Subramanian et al., 2006a).

THTR-2 mediates the transmembrane uptake of thiamine (vitamin B1) via a proton anti-port mechanism (Rajgopal et al., 2001). This thiamine uptake process was reported to be temperature-, energy- and pH-dependent (Ashokkumar et al., 2006; Subramanian et al., 2007), and is adaptively regulated by the extracellular thiamine level through transcriptional regulation of the SLC19A3 gene (Nabokina et al., 2013). In human intestinal epithelial cells, THTR-2 interacts with the human transmembrane 4 super-family 4 (TM4SF4) and influences the intestinal thiamine uptake (Subramanian et al., 2014).

THTR-2 protein belongs to the SLC19 gene family (folate/thiamine transporter family) of solute carriers. Two other members of the family are SLC19A1 (a folate transporter) and SLC19A2 (a thiamine transporter, THTR-1), which share 42% and 53% amino acid sequence identities to the human THTR-2 (Ganapathy et al., 2004). The human SLC19A3 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, and mosquito.

Mutations in SLC19A3 (homozygous and compound heterozygous) have been associated with different neurological disorders, including biotin responsive basal ganglia disease (BBGD), Wernickes-like encephalopathy, and Leigh syndrome. The pathogenic mutations identified to date include p.Gly23Val, p.Thr422Ala (Zeng et al., 2005), p.Lys44Glu, p.Glu320Gln (Kono et al., 2009; Yamada et al., 2010), c.74dupT, IVS3-14A>G (Debs et al., 2010), p.Ser7* (Gerards et al., 2013), p.Gln393*, p.Ser181Pro, p.Leu385Arg, p.Tyr169*, p.Ser176Tyr, p.Val299fs and p.Ser444Arg (Kevelam et al., 2013).