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Human diseases caused by or associated with transporters
| TC | Disease | Protein Name | Description | Accession # | OMIM |
| 1.A.1.15.2 | Benign Neonatal Epilepsy | KCNQ2 | 6 TMS voltage-gated K+ channel, KCNQ2 (mutations cause benign familial neonatal convulsions (BNFC; epilepsy)) (forms homotetramers or heterotetramers with KCNQ3) (Soldovieri et al., 2006; Uehara et al., 2008) | O43526 | 121200 |
| 1.A.1.15.3 | Benign Neonatal Epilepsy 2 | KCNQ3 | 6 TMS voltage-gated K+ channel, KCNQ3 (mutations cause benign familial neonatal convulsions (BNFC; epilepsy)) (forms homotetramers or heterotetramers with KCNQ2) (Soldovieri et al., 2006; Uehara et al., 2008) | O43525 | 121201 |
| 1.A.1.15.4 | Autosomal Dominant Nonsydromic Sensorineural Deafness | KCNQ4 | 6 TMS cell volume sensitive, voltage-gated K+ channel, KCNQ4 (mutations cause DFNA2, an autosomal dominant form of progressive hearing loss) (forms homomers or heteromers with KCNQ3) (localized to the basal membrane of cochlear outer hair cells and in several nuclei of the central auditory pathway in the brainstem). Four splice variants form heterotetramers; each subunit has different voltage and calmodulin-sensitivities (Xu et al., 2007) | P56696 | 600101 |
| 1.A.1.15.6 | Jervell and Lange-Nielsen Syndrome | KCNQ1 | K+ voltage-gated channel, KQT-like subfamily; Kv7.1; KCNQ1 (regulated by KCNE peptides which affect voltage sensor equilibrium; Rocheleau and Kobertz, 2007). Almost 300 mutations of KCNQ1 have been identified in patients, and most are linked to the long QT syndrome (Peroz et al., 2008). | P51787 | 220400 |
| 1.A.1.15.6 | Long QT Syndrome | KCNQ1 | K+ voltage-gated channel, KQT-like subfamily; Kv7.1; KCNQ1 (regulated by KCNE peptides which affect voltage sensor equilibrium; Rocheleau and Kobertz, 2007). Almost 300 mutations of KCNQ1 have been identified in patients, and most are linked to the long QT syndrome (Peroz et al., 2008). | P51787 | 192500 |
| 2.A.1.1.28 | HTLV-1 Associated Myelopathy | Gtr1 aka SLC2A1 aka GLUT1 | The erythrocyte/brain hexose facilitator, Gtr1 or Glut1. Also transports D-glucose, dehydroascorbate, and the flavonone, quercetin, via one channel and water via a distinct channel. Sugar transport has been suggested to function via a sliding mechanism involving several sugar binding sites (Cunningham et al., 2006). (Receptor for human T-cell leukemia virus (HTLV)) (Manel et al., 2003). Regulated by stomatin to take up dehydroascorbate (Montel-Hagen et al., 2008). Mutations cause Glut1 deficiency syndrome, a human encephalopathy that results from decreased glucose flux through the blood brain barrier (Pascual et al., 2008). | P11166 | 159580 |
| 2.A.1.1.28 | Neurofibromatosis | Gtr1 aka SLC2A1 aka GLUT1 | The erythrocyte/brain hexose facilitator, Gtr1 or Glut1. Also transports D-glucose, dehydroascorbate, and the flavonone, quercetin, via one channel and water via a distinct channel. Sugar transport has been suggested to function via a sliding mechanism involving several sugar binding sites (Cunningham et al., 2006). (Receptor for human T-cell leukemia virus (HTLV)) (Manel et al., 2003). Regulated by stomatin to take up dehydroascorbate (Montel-Hagen et al., 2008). Mutations cause Glut1 deficiency syndrome, a human encephalopathy that results from decreased glucose flux through the blood brain barrier (Pascual et al., 2008). | P11166 | 162200 |
| 2.A.1.4.5 | Gierke's Disease (Glycogen Storage Disease 1b) | G6PU aka GSD1b aka G6PT1 aka G6PT | Microsomal glucose-6-P:Pi antiporter (glycogen storage disease (GSD1b and 1c); Gierke's disease protein) (SLC37A2; in mice, associated with white adipose tissue obesity and expressed at high levels in macrophage) (4 isoforms present in humans; Chen et al., 2008) | O43826 | 232220 |
| 2.A.1.14.10 | Infantile Sialic Acid Storage Disorder | Sialin | Lysosomal sialate transporter (sialate storage disease protein) | Q9UGH0 | 269920 |
| 2.A.1.14.10 | Salla Disease | Sialin | Lysosomal sialate transporter (sialate storage disease protein) | Q9UGH0 | 604369 |
| 2.A.6.6.1 | Niemann-Pick Disease Type C1 | NPC1 aka NPC | Niemann-Pick C1 AND C2 disease proteins (together may form a possible lipid/cholesterol exporter from lysosomes to other cellular sites) (Sleat et al., 2004). NPC1 deficiency causes lysosomal retention of cholesterol, sphingolipids, phospholipids, and glycolipids (Infante et al., 2007). NPC1 binds cholesterol, 25-hydroxycholesterol and various oxysterols (Infante et al., 2008). | O15118 | 257220 |
| 2.A.7.16.1 | Congenital Disorder of Glycosylation (Leukocyte Adhesion Deficiency) | GFT aka FUCT1 | The GDP fucose transporter (GFT) (defective in human leukocyte adhesion disease II) | Q96A29 | 266265 |
| 2.A.29.2.4 | 2-oxoadipate acidemia | ODC aka SLC25A21 | Mammalian oxodicarboxylate carrier (ODC) (transports 2-oxoadipate and 2-oxoglutarate in an antiport reaction; also transports less well: pimelate, 2-oxopimleate, 2-amino adipate, oxaloacetate, and citrate) (Defects cause 2-oxoadipate acidemia, an inborn error of metabolism) | Q9BQT8 | 607571 |
| 2.A.29.3.2 | UPC1 Obesity protein | Mitochondrial brown fat uncoupling protein 1 (UCP1) (thermogenin) aka obesity protein (SLC25A7) | Mitochondrial brown fat uncoupling protein 1 (UCP1) (thermogenin); obesity protein (SLC25A7) | P25874 | 113730 |
| 2.A.29.12.1 | Graves Disease | SLC25A16 aka GDA aka GDC | Grave’s disease carrier (GDC) protein (may transport coenzyme A or a coenzyme A precursor) (SLC25A16 for the human orthologue) | Q01888 | 275000 |
| 2.A.29.14.2 | Citrullinemia Type II | CMC2 aka SLC25A13 or ARALAR2 | Mitochondrial Ca2+-activated aspartate/glutamate antiporter carrier with Ca2+-binding EF-hand domain, Citrin (defects in humans cause type II citrullinemia) | Q9UJS0 | 603471 |
| 2.A.30.5.3 | Andermann Syndrome | KCC3 | KCl symporter, KCC3 (Andermann Syndrome protein) | Q9UHW9 | 218000 |
| 2.A.45.2.1 | Oculocutaneous Albinism Type II | P aka OCA2 | P-protein; possible tyrosine transporter (also called "melanocyte-specific transporter", "oculocutaneous albinism-related protein" and "pink-eyed dilution gene product") | Q04671 | 203200 |
| 2.A.48.2.1 | Thiamine-Responsive Megaloblastic Anemia Syndrome | THT1 aka THTR-1 aka SLC19A2 aka TRMA | Thiamine uptake transporter-1, THTR-1 (the thiamine-responsive megaloblastic anemia (TRMA) protein) | O60779 | 249270 |
| 2.A.53.2.1 | Diastrophic Dysplasia | DTD aka SLC26A2 aka DTDST | Sulfate/anion transporter (diastrophic dysplasia protein) (SLC26A2) | P50443 | 222600 |
| 3.A.1.201.2 | Progressive Familial Intrahepatic Cholestasis 2 | AB11 aka BSEP aka SPGP aka ABCB11 | Bile salt export pump, BSEP or SPGP (associated with progressive familial intrahepatic cholestasis-2 (also called ABCB11) and benign recurrent intrahepatic cholestasis (Kagawa et al., 2007)). Unconjugaged bile salts and glycine conjugates > taurine conjugates. | O95342 | 601847 |
| 3.A.1.201.3 | Progressive Familial Intrahepatic Cholestasis 3 | MDR3 aka PGY3 aka ABCB4 | Short chain fatty acid phosphatidylcholine translocase (phospholipid flippase), MDR3 (associated with progressive familial intrahepatic cholestasis-3). (Narrow drug specificity relative to MDR1. Exports digoxin, paclitaxel, vinblastin and bile acids.) (also called ABCB4) | P21439 | 602347 |
| 3.A.1.202.1 | Cystic Fibrosis | CFTR aka ABCC7 | Cystic fibrosis transmembrane conductance regulator (CFTR)(also called ABCC7); cyclic AMP-dependent chloride channel; also catalyzes nucleotide (ATP-ADP)-dependent glutathione flux (Kogan et al., 2003) (may also activate inward rectifying K+ channels). The underlying mechanism by which ATP hydrolysis controls channel opening is described by Gadsby et al., (2006). The most common cause of cystic fibrosis (CF) is defective folding of a cystic fibrosis transmembrane conductance regulator (CFTR) mutant lacking Phe508 (DeltaF508)(Riordan, 2008). The DeltaF508 protein appears to be trapped in a prefolded state with incomplete packing of the transmembrane segments, a defect that can be repaired by direct interaction with correctors such as corr-4a, VRT-325, and VRT-532 (Wang et al., 2007). CFTR interacts directly with MRP4 (3.A.1.208.7) to control Cl- secretion (Li et al., 2007). It has intrinsic adenylate kinase activity that may be of functional importance (Randak and Welsh, 2007). The intact CFTR protein mediates ATPase rather than adenylate kinase activity (Ramjeesingh et al., 2008) | P13569 | 219700 |
| 3.A.1.203.1 | Zellweger Syndrome | ABD3 aka PMP70 aka PXMP1 aka ABCD3 | Peroxysomal long chain fatty acyl (LCFA) transporter associated with Zellweger Syndrome | P28288 | 214100 |
| 3.A.1.203.3 | Adrenoleukodystrophy | ABCD1 aka ALD | The peroxysomal long chain fatty acid (LCFA) half transporter, ABCD1 (ALD, the adrenoleukodystrophy protein) (functions as a homodimer and accepts acyl-CoA esters (van Roermund et al. 2008)). | P33897 | 300100 |
| 3.A.1.208.2 | Dubin-Johnson Syndrome | MRP2 aka MRP aka cMOAT aka ABCC2 aka cMOAT1 aka cMRP | Hepatic canalicular conjugate exporter (the Dubin-Johnson Syndrome protein) (transports bilirubin glucuronides; E2 17 β glucuronide, dianionic bile salts such as taurocholate, taurochenodeoxycholate sulfate and taurolithocholate sulfate; reduced glutathione; glutathione conjugates; cysteinyl leukotrienes; arsenic-glutathione complexes and glutathione disulfide; also exports anthracyclines, epipodophyllotosine, Vinca alkaloids, cisplatin, methotrexate, and the protease inhibitor, lopinavir) (also called ABCC2) | Q92887 | 237500 |
| 3.A.1.208.4 | Nesidioblastosis of the Pancreas (Persistent Hyperinsulinemic Hypoglycemia of Infancy) | ACC8 aka SUR1 aka SUR aka ABCC8 | SUR1 sulfonylurea receptor; subunit and regulator of α-cell ATP-sensitive K+ channel (TC #1.A.2); determines ATP sensitivity; no inherent transport function known; associated with persistent hyperinsulinemic hypoglycemia of infancy due to focal adenomatous hyperplasia (also called ABCC8). Gain-of-function mutations in the genes encoding the ATP-sensitive potassium (K(ATP)) channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) cause neonatal diabetes mellitus. Because mutant channels are inhibited less strongly by MgATP, this increases K(ATP) currents in pancreatic beta cells, thus reducing insulin secretion and producing diabetes (de Wet et al., 2007). | Q09428 | 256450 |
| 3.A.1.208.10 | Pseudoxanthoma Elasticum | ABCC6 aka MRPb aka MRP6 aka ARA | Multidrug (anthracycline) resistance organic anion efflux pump (ABC-C6; MRP6; MOAT-E - the pseudoxanthoma elasticum disease protein) exports glutathione conjugates including lencotriene C4, DNP, and N-ethylmaleimide S-glutathione; also exports anthracyclines, epipodophyllotoxins, cisplatin, and probably exports probenecid, benzbromarone and indomethacin. | O95255 | 264800 |
| 3.A.1.209.1 | Bare Lymphocyte Syndrome Type I | TAP2 aka ABCB3 aka PSF2 aka RING11 aka Y1 | MHC heterodimeric peptide exporter (TAP) (from cytoplasm to the endoplasmic reticulum) (TAP1=ABCB2; TAP2=ABCB3) (defects in TAP1 or TAP2 cause immunodeficiency) (TAP1/TAP2 is stabilized by tapasin isoforms 1, 2 and 3) (Raghuraman et al., 2002). TAP1 has 10 TMSs, 4 unique N-terminal TMSs and 6 TMSs that form the translocation pore with N- and C-termini in the cytosol (Schrodt et al., 2006). The TAP2 nucleotide binding site appears to be the main catalytic active site driving transport suggesting asymmetry in the transporter (Perria et al., 2006). | Q03519 | 604571 |
| 3.A.1.209.1 | Insulin-Dependent Diabetes Mellitus | TAP1 aka ABCB2 aka PSF1 aka RING4 aka Y3 | MHC heterodimeric peptide exporter (TAP) (from cytoplasm to the endoplasmic reticulum) (TAP1=ABCB2; TAP2=ABCB3) (defects in TAP1 or TAP2 cause immunodeficiency) (TAP1/TAP2 is stabilized by tapasin isoforms 1, 2 and 3) (Raghuraman et al., 2002). TAP1 has 10 TMSs, 4 unique N-terminal TMSs and 6 TMSs that form the translocation pore with N- and C-termini in the cytosol (Schrodt et al., 2006). The TAP2 nucleotide binding site appears to be the main catalytic active site driving transport suggesting asymmetry in the transporter (Perria et al., 2006). | Q03518 | 222100 |
| 3.A.1.210.4 | Anemia, Sideroblastic, and Spinocerebellar Ataxia | ABC7 aka ABCB7 | ABC7 iron transporter (X-linked sideroblastis anemia protein) (also called ABCB7) | O75027 | 301310 |
| 3.A.1.211.1 | Tangier Disease | ABC1 aka ABCA1 | The cholesterol/phospholipid flippase, ABC1 (called ABCA1 in humans; Tangier disease proteins; 2261 aas; sp: O95477). An amphipathic helical region of the N-terminal barrel of the phospholipid transfer protein (PLTP) is critical for ABCA1-dependent cholesterol efflux (Oram et al., 2008). PLTP helix 144-163 removes lipid domains formed by ABCA1, stabilizing ABCA1, interacting with phospholipids, and promoting phospholipid transfer by direct interactions with ABCA1. | P41233 | 205400 |
| 3.A.1.211.2 | Stargardt Disease 1 | RIM aka ABCR aka ABCA4 | The retinal-specific ABC transporter (RIM protein, ABCR or ABCA4) (Stargardt's disease protein, involved in retinal/macular degeneration) in the rod outer segment. May flip retinal, or more likely, N-retinylidene-phosphatidylethanolamine, a product generated from the photobleaching of rhodopsin, from the lumen to the cytoplasmic side of disc membranes following the photobleaching of rhodopsin, insuring that retinoids do not accumulate in disc membranes (Molday, 2007; Molday et al. 2009) | P78363 | 248200 |
| 3.A.1.302.3 | Adrenoleukodystrophy | ABCD1 aka ALD | Functions as a homodimer and accepts acyl-CoA esters (van Roermund et al. 2008). | P33897 | 300100 |
| 3.A.3.2.5 | Hailey-Hailey Disease | hSPCA1 aka ATC1 aka ATP2C1 aka PMR1L aka KIAA1347 | The Golgi Ca2+, Mn2+-ATPase, hSPCA1 (efflux) (the Hailey-Hailey disease protein). Involved in responses to golgi stress, apoptosis and midgestational death (Okunade et al., 2007) | P98194 | 169600 |
| 3.A.3.2.7 | Darier-White Disease | ATP2A2 aka ATP2B aka SERCA2 | The sarco/endoplasmic reticulum Ca2+-ATPase, SERCA2b (encoded by the ATPLA2 gene) (Darier's disease protein) (Ahn et al., 2003) (SERCA1 functions as a heat generator in mitochondria of brown adipose tissue; de Meis et al., 2006). Functions as a Ca2+:H+ antiporter (Karjalainen et al., 2007). Capsaicin converts SERCA to a Ca2+ non-transporting ATPase that generates heat. Capsaicin is the first natural drug that augments uncoupled SERCA, resulting in thermogenesis (Mahmmoud, 2008b). | P16615 | 124200 |
| 3.A.3.5.3 | Wilson's Disease | AT7B aka ATP7B aka WND aka PWD aka WC1 | Cu+-, Ag+-ATPase (efflux from the cytosol into the secretory pathway) (Barnes et al., 2005); ATP7B (Wilson's disease protein, α-chain) (continuously expressed in Purkinje neurons). It delivers Cu+ to the ferroxidase, ceruloplasmin, in liver. May also transport Fe2+ (Takeda et al., 2005). | P35670 | 277900 |
| 3.A.3.5.6 | Cutis Laxa | ATP7A aka MNK aka MC1 | Cu+-ATPase, ATP7A (MNK or Mc1) (efflux from the cytosol into the secretory pathway) (Menkes disease protein, α-chain). Expressed in Purkinje cells early in development and later in Bergmann glia. In melanocytes, it delivers Cu2+ to tyrosinase (Barnes et al., 2005). ATP7A has dual functions: 1) it incorporates copper into copper-dependent enzymes; and 2) it maintains intracellular copper levels by removing excess copper from the cytosol. To accomplish both functions, the protein traffics between different cellular locations, depending on copper levels (Bertini and Rosato, 2008). | Q04656 | 304150 |
| 3.A.3.5.6 | Menkes Disease | ATP7A aka MNK aka MC1 | Cu+-ATPase, ATP7A (MNK or Mc1) (efflux from the cytosol into the secretory pathway) (Menkes disease protein, α-chain). Expressed in Purkinje cells early in development and later in Bergmann glia. In melanocytes, it delivers Cu2+ to tyrosinase (Barnes et al., 2005). ATP7A has dual functions: 1) it incorporates copper into copper-dependent enzymes; and 2) it maintains intracellular copper levels by removing excess copper from the cytosol. To accomplish both functions, the protein traffics between different cellular locations, depending on copper levels (Bertini and Rosato, 2008). | Q04656 | 309400 |