| Tbio | Thiamine transporter 2 |
Mediates high affinity thiamine uptake, probably via a proton anti-port mechanism. Has no folate transport activity.
This gene encodes a ubiquitously expressed transmembrane thiamine transporter that lacks folate transport activity. Mutations in this gene cause biotin-responsive basal ganglia disease (BBGD); a recessive disorder manifested in childhood that progresses to chronic encephalopathy, dystonia, quadriparesis, and death if untreated. Patients with BBGD have bilateral necrosis in the head of the caudate nucleus and in the putamen. Administration of high doses of biotin in the early progression of the disorder eliminates pathological symptoms while delayed treatment results in residual paraparesis, mild mental retardation, or dystonia. Administration of thiamine is ineffective in the treatment of this disorder. Experiments have failed to show that this protein can transport biotin. Mutations in this gene also cause a Wernicke's-like encephalopathy.[provided by RefSeq, Jan 2010]
This gene encodes a ubiquitously expressed transmembrane thiamine transporter that lacks folate transport activity. Mutations in this gene cause biotin-responsive basal ganglia disease (BBGD); a recessive disorder manifested in childhood that progresses to chronic encephalopathy, dystonia, quadriparesis, and death if untreated. Patients with BBGD have bilateral necrosis in the head of the caudate nucleus and in the putamen. Administration of high doses of biotin in the early progression of the disorder eliminates pathological symptoms while delayed treatment results in residual paraparesis, mild mental retardation, or dystonia. Administration of thiamine is ineffective in the treatment of this disorder. Experiments have failed to show that this protein can transport biotin. Mutations in this gene also cause a Wernicke's-like encephalopathy.[provided by RefSeq, Jan 2010]
Comments
| Disease | Target Count |
|---|---|
| Basal Ganglia Diseases | 12 |
| Basal ganglia disease, biotin-responsive | 1 |
| Disease | Target Count | P-value |
|---|---|---|
| lung adenocarcinoma | 2714 | 2.18127235998003E-22 |
| non-small cell lung carcinoma | 413 | 1.60836343544729E-20 |
| lung carcinoma | 2844 | 2.16007116911876E-20 |
| ovarian cancer | 8492 | 2.86404731933903E-8 |
| lung cancer | 4473 | 5.19999986951239E-7 |
| colon cancer | 1475 | 1.82685226852062E-6 |
| ductal carcinoma in situ | 1745 | 2.18486053068042E-4 |
| invasive ductal carcinoma | 2950 | 6.57443232013714E-4 |
| breast carcinoma | 1614 | 0.0070979334788754 |
| fibroadenoma | 557 | 0.0141303460320407 |
| active Crohn's disease | 918 | 0.0175963937824782 |
| active ulcerative colitis | 477 | 0.0266114221597118 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| biotin-responsive basal ganglia disease | 8 | 0.0 | 5.0 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Leigh disease | 81 | 4.336 | 2.2 |
| Beriberi | 13 | 4.148 | 2.1 |
| Brain disease | 84 | 3.686 | 1.8 |
| Biotin deficiency | 9 | 3.665 | 1.8 |
| Megaloblastic anemia | 18 | 3.652 | 1.8 |
| Pyruvate decarboxylase deficiency | 15 | 3.079 | 1.5 |
| Disease | Target Count |
|---|---|
| Thiamine metabolism dysfunction syndrome 2, biotin- or thiamine-responsive type | 1 |
| Disease | log2 FC | p |
|---|---|---|
| non-small cell lung carcinoma | -1.900 | 0.000 |
| lung cancer | -3.300 | 0.000 |
| colon cancer | -2.900 | 0.000 |
| active Crohn's disease | -1.229 | 0.018 |
| active ulcerative colitis | -1.239 | 0.027 |
| breast carcinoma | -1.700 | 0.007 |
| fibroadenoma | -2.600 | 0.014 |
| lung adenocarcinoma | -2.300 | 0.000 |
| lung carcinoma | -3.000 | 0.000 |
| ductal carcinoma in situ | -3.900 | 0.000 |
| invasive ductal carcinoma | -4.400 | 0.001 |
| ovarian cancer | -1.200 | 0.000 |
| Species | Source |
|---|---|
| Chimp | OMA EggNOG |
| Macaque | OMA EggNOG Inparanoid |
| Mouse | OMA EggNOG Inparanoid |
| Rat | OMA Inparanoid |
| Dog | OMA EggNOG |
| Horse | OMA EggNOG |
| Cow | OMA EggNOG Inparanoid |
| Pig | OMA EggNOG |
| Opossum | OMA Inparanoid |
| Opossum | OMA EggNOG |
| C. elegans | OMA Inparanoid |
| PMID | Text |
|---|---|
| 26863430 | large genomic deletions occur in the regulatory region of SLC19A3 in Biotin-Thiamine-Responsive Basal Ganglia Encephalopathy |
| 26528626 | Species differences in the substrate specificity of THTR-2 between human and mouse orthologues were observed. |
| 24667918 | Microarray analysis indicates HIV-1 Tat-induced upregulation of solute carrier family 19, member 3 (SLC19A3) in primary human brain microvascular endothelial cells |
| 24667528 | Genetic variation in the SLC19A3 thiamine transporter at 2:228563818T/C may make a modest contribution towards the genetic susceptibility to alcohol dependence syndrome. |
| 24372704 | This study provided evidence that biotin-thiamine-responsive basal ganglia disease is the result of SLC19A2 mutation. |
| 24282057 | TM4SF4 interacts with hTHTR-2 and influences the physiological function of the thiamine transporter in human intestinal epithelial cells. |
| 23989004 | These studies demonstrate that the human intestinal thiamine uptake is adaptively regulated by the extracellular substrate level via transcriptional regulation of the THTR-2 system, and that SP1 transcriptional factor is involved in this regulation. |
| 23482991 | A new, severe phenotype of SLC19A3 is identified in early-infantile, lethal encephalopathy characterized by subtotal brain degeneration. |
| 23423671 | Our data shows that SLC19A3 is a new candidate for mutation screening in patients with Leigh syndrome |
| 23285265 | Glucose-induced decreased expression of thiamine transporters in the tubular epithelium may mediate renal mishandling of thiamine in diabetes. |
| More... |
MDCYRTSLSSSWIYPTVILCLFGFFSMMRPSEPFLIPYLSGPDKNLTSAEITNEIFPVWTYSYLVLLLPV 1 - 70 FVLTDYVRYKPVIILQGISFIITWLLLLFGQGVKTMQVVEFFYGMVTAAEVAYYAYIYSVVSPEHYQRVS 71 - 140 GYCRSVTLAAYTAGSVLAQLLVSLANMSYFYLNVISLASVSVAFLFSLFLPMPKKSMFFHAKPSREIKKS 141 - 210 SSVNPVLEETHEGEAPGCEEQKPTSEILSTSGKLNKGQLNSLKPSNVTVDVFVQWFQDLKECYSSKRLFY 211 - 280 WSLWWAFATAGFNQVLNYVQILWDYKAPSQDSSIYNGAVEAIATFGGAVAAFAVGYVKVNWDLLGELALV 281 - 350 VFSVVNAGSLFLMHYTANIWACYAGYLIFKSSYMLLITIAVFQIAVNLNVERYALVFGINTFIALVIQTI 351 - 420 MTVIVVDQRGLNLPVSIQFLVYGSYFAVIAGIFLMRSMYITYSTKSQKDVQSPAPSENPDVSHPEEESNI 421 - 490 IMSTKL 491 - 496 //
| PMID | Year | Title |
|---|---|---|
| 26863430 | 2016 | Novel SLC19A3 Promoter Deletion and Allelic Silencing in Biotin-Thiamine-Responsive Basal Ganglia Encephalopathy. |
| 26528626 | 2015 | Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). |
| 24667528 | 2014 | Evidence for genetic susceptibility to the alcohol dependence syndrome from the thiamine transporter 2 gene solute carrier SLC19A3. |
| 24372704 | 2014 | Stress-induced upregulation of SLC19A3 is impaired in biotin-thiamine-responsive basal ganglia disease. |
| 24282057 | 2014 | Association of TM4SF4 with the human thiamine transporter-2 in intestinal epithelial cells. |
| 24275569 | 2014 | An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. |
| 23989004 | 2013 | Adaptive regulation of human intestinal thiamine uptake by extracellular substrate level: a role for THTR-2 transcriptional regulation. |
| 23482991 | 2013 | Exome sequencing reveals mutated SLC19A3 in patients with an early-infantile, lethal encephalopathy. |
| 23423671 | 2013 | Exome sequencing reveals a novel Moroccan founder mutation in SLC19A3 as a new cause of early-childhood fatal Leigh syndrome. |
| 23285265 | 2012 | Glucose-induced down regulation of thiamine transporters in the kidney proximal tubular epithelium produces thiamine insufficiency in diabetes. |
| More... |
