SLC22A12

Last updated
SLC22A12
Identifiers
Aliases SLC22A12 , solute carrier family 22 (organic anion/urate transporter), member 12, OAT4L, RST, URAT1, solute carrier family 22 member 12
External IDs OMIM: 607096 MGI: 1195269 HomoloGene: 56442 GeneCards: SLC22A12
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001276326
NM_001276327
NM_144585
NM_153378

NM_009203

RefSeq (protein)

NP_001263255
NP_001263256
NP_653186
NP_700357

NP_033229

Location (UCSC) Chr 11: 64.59 – 64.6 Mb Chr 19: 6.59 – 6.59 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Solute carrier family 22 (organic anion/cation transporter), member 12, also known as SLC22A12 and URAT1, is a protein which in humans is encoded by the SLC22A12 gene. [5] [6]

Contents

Function

The protein encoded by this gene is a urate transporter and urate-anion exchanger which regulates the level of urate in the blood. This protein is an integral membrane protein primarily found in kidney. Two transcript variants encoding different isoforms have been found for this gene. [5]

Clinical significance

Numerous single nucleotide polymorphisms of this gene are significantly associated with altered (increased or decreased) reabsorption of uric acid by the kidneys. [7] [8] Respectively, these altered rates of reabsorption contribute to hyperuricemia and hypouricemia.

Interactions

SLC22A12 has been shown to have a protein-protein interaction with PDZK1. [9]

Inhibition

Lesinurad,Ruzinurad and dotinurad are urate transporter inhibitors that have been approved to treat gout. [10] [11] Lesinurad enhances urate excretion by inhibition the tubular re-absorption. Probenecid also facilitates uric acid secretion. [12] [13]

See also

Related Research Articles

<span class="mw-page-title-main">Uric acid</span> Organic compound

Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of purine nucleotides, and it is a normal component of urine. High blood concentrations of uric acid can lead to gout and are associated with other medical conditions, including diabetes and the formation of ammonium acid urate kidney stones.

<span class="mw-page-title-main">Hyperuricemia</span> Medical condition

Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7 mg/dL for men, and 5.5 mg/dL for youth are defined as hyperuricemia. The amount of urate in the body depends on the balance between the amount of purines eaten in food, the amount of urate synthesised within the body, and the amount of urate that is excreted in urine or through the gastrointestinal tract. Hyperuricemia may be the result of increased production of uric acid, decreased excretion of uric acid, or both increased production and reduced excretion.

<span class="mw-page-title-main">Urate oxidase</span> Pseudogene in the species Homo sapiens

The enzyme urate oxidase (UO), uricase or factor-independent urate hydroxylase, absent in humans, catalyzes the oxidation of uric acid to 5-hydroxyisourate:

Protein toxicity is the effect of the buildup of protein metabolic waste compounds, like urea, uric acid, ammonia, and creatinine. Protein toxicity has many causes, including urea cycle disorders, genetic mutations, excessive protein intake, and insufficient kidney function, such as chronic kidney disease and acute kidney injury. Symptoms of protein toxicity include unexplained vomiting and loss of appetite. Untreated protein toxicity can lead to serious complications such as seizures, encephalopathy, further kidney damage, and even death.

<span class="mw-page-title-main">Xanthinuria</span> Medical condition

Xanthinuria, also known as xanthine oxidase deficiency, is a rare genetic disorder causing the accumulation of xanthine. It is caused by a deficiency of the enzyme xanthine oxidase.

Uricosuric medications (drugs) are substances that increase the excretion of uric acid in the urine, thus reducing the concentration of uric acid in blood plasma. In general, this effect is achieved by action on the proximal tubule of the kidney. Drugs that reduce blood uric acid are not all uricosurics; blood uric acid can be reduced by other mechanisms.

<span class="mw-page-title-main">Probenecid</span> Chemical compound

Probenecid, also sold under the brand name Probalan, is a medication that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia.

<span class="mw-page-title-main">Hypouricemia</span> Medical condition

Hypouricemia or hypouricaemia is a level of uric acid in blood serum that is below normal. In humans, the normal range of this blood component has a lower threshold set variously in the range of 2 mg/dL to 4 mg/dL, while the upper threshold is 530 μmol/L (6 mg/dL) for women and 619 μmol/L (7 mg/dL) for men. Hypouricemia usually is benign and sometimes is a sign of a medical condition.

<span class="mw-page-title-main">Neutral and basic amino acid transport protein rBAT</span> Protein-coding gene in the species Homo sapiens

Neutral and basic amino acid transport protein rBAT is a protein that in humans is encoded by the SLC3A1 gene.

<span class="mw-page-title-main">Multidrug resistance-associated protein 2</span> Protein-coding gene in the species Homo sapiens

Multidrug resistance-associated protein 2 (MRP2) also called canalicular multispecific organic anion transporter 1 (cMOAT) or ATP-binding cassette sub-family C member 2 (ABCC2) is a protein that in humans is encoded by the ABCC2 gene.

<span class="mw-page-title-main">PDZK1</span> Protein-coding gene in the species Homo sapiens

Na(+)/H(+) exchange regulatory cofactor NHE-RF3 is a protein that in humans is encoded by the PDZK1 gene.

<span class="mw-page-title-main">SLC22A11</span> Protein-coding gene in the species Homo sapiens

Solute carrier family 22 member 11 is a protein that in humans is encoded by the SLC22A11 gene.

<span class="mw-page-title-main">SLC22A8</span> Protein-coding gene in the species Homo sapiens

Solute carrier family 22 member 8, or organic anion transporter 3 (OAT3), is a protein that in humans is encoded by the SLC22A8 gene.

<span class="mw-page-title-main">SLC22A7</span> Protein-coding gene in the species Homo sapiens

Solute carrier family 22 member 7 is a protein that in humans is encoded by the gene SLC22A7.

<span class="mw-page-title-main">SLC22A9</span> Protein-coding gene in the species Homo sapiens

Solute carrier family 22 member 9 is a protein that in humans is encoded by the SLC22A9 gene.

<span class="mw-page-title-main">Sodium-dependent phosphate transport protein 2C</span> Protein-coding gene in the species Homo sapiens

Sodium-dependent phosphate transport protein 2C is a protein that in humans is encoded by the SLC34A3 gene.

<span class="mw-page-title-main">Asc-type amino acid transporter 1</span> Protein-coding gene in the species Homo sapiens

Asc-type amino acid transporter 1 (Asc-1) is a protein that in humans is encoded by the SLC7A10 gene.

<span class="mw-page-title-main">Organic anion transporter 1</span> Protein-coding gene in the species Homo sapiens

The organic anion transporter 1 (OAT1) also known as solute carrier family 22 member 6 (SLC22A6) is a protein that in humans is encoded by the SLC22A6 gene. It is a member of the organic anion transporter (OAT) family of proteins. OAT1 is a transmembrane protein that is expressed in the brain, the placenta, the eyes, smooth muscles, and the basolateral membrane of proximal tubular cells of the kidneys. It plays a central role in renal organic anion transport. Along with OAT3, OAT1 mediates the uptake of a wide range of relatively small and hydrophilic organic anions from plasma into the cytoplasm of the proximal tubular cells of the kidneys. From there, these substrates are transported into the lumen of the nephrons of the kidneys for excretion. OAT1 homologs have been identified in rats, mice, rabbits, pigs, flounders, and nematodes.

<span class="mw-page-title-main">Monocarboxylate transporter 10</span> Protein-coding gene in the species Homo sapiens

Monocarboxylate transporter 10, also known as aromatic amino acid transporter 1 and T-type amino acid transporter 1 (TAT1) and solute carrier family 16 member 10 (SLC16A10), is a protein that in humans is encoded by the SLC16A10 gene. SLC16A10 is a member of the solute carrier family.

<span class="mw-page-title-main">SLC17A3</span> Protein-coding gene in the species Homo sapiens

Solute carrier family 17, member 3 is a protein that in humans is encoded by the SLC17A3 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000197891 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000061742 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 "Entrez Gene: SLC22A12 solute carrier family 22 (organic anion/cation transporter), member 12".
  6. Enomoto A, Kimura H, Chairoungdua A, Shigeta Y, Jutabha P, Cha SH, Hosoyamada M, Takeda M, Sekine T, Igarashi T, Matsuo H, Kikuchi Y, Oda T, Ichida K, Hosoya T, Shimokata K, Niwa T, Kanai Y, Endou H (May 2002). "Molecular identification of a renal urate anion exchanger that regulates blood urate levels". Nature. 417 (6887): 447–52. Bibcode:2002Natur.417..447E. doi:10.1038/nature742. PMID   12024214. S2CID   4417844.
  7. Graessler J, Graessler A, Unger S, Kopprasch S, Tausche AK, Kuhlisch E, Schroeder HE (January 2006). "Association of the human urate transporter 1 with reduced renal uric acid excretion and hyperuricemia in a German Caucasian population". Arthritis Rheum. 54 (1): 292–300. doi:10.1002/art.21499. PMID   16385546.
  8. Wakida N, Tuyen DG, Adachi M, Miyoshi T, Nonoguchi H, Oka T, Ueda O, Tazawa M, Kurihara S, Yoneta Y, Shimada H, Oda T, Kikuchi Y, Matsuo H, Hosoyamada M, Endou H, Otagiri M, Tomita K, Kitamura K (April 2005). "Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia". J. Clin. Endocrinol. Metab. 90 (4): 2169–74. doi: 10.1210/jc.2004-1111 . PMID   15634722.
  9. Gisler SM, Pribanic S, Bacic D, Forrer P, Gantenbein A, Sabourin LA, Tsuji A, Zhao ZS, Manser E, Biber J, Murer H (November 2003). "PDZK1: I. a major scaffolder in brush borders of proximal tubular cells". Kidney Int. 64 (5): 1733–45. doi: 10.1046/j.1523-1755.2003.00266.x . PMID   14531806.
  10. "FDA approves Zurampic to treat high blood uric acid levels associated with gout". United States Food and Drug Administration. 22 December 2015.
  11. "List of Approved Products" (PDF). Pharmaceuticals and Medical Devices Agency.
  12. Hsyu PH, Gisclon LG, Hui AC, Giacomini KM (January 1988). "Interactions of organic anions with the organic cation transporter in renal BBMV". The American Journal of Physiology. 254 (1 Pt 2): F56–61. doi:10.1152/ajprenal.1988.254.1.F56. PMID   2962517.
  13. Silverman W, Locovei S, Dahl G (September 2008). "Probenecid, a gout remedy, inhibits pannexin 1 channels". American Journal of Physiology. Cell Physiology. 295 (3): C761–7. doi:10.1152/ajpcell.00227.2008. PMC   2544448 . PMID   18596212.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.