Defective SLC22A12 does not exchange extracellular urate for cytosolic LACT

Stable Identifier
Reaction [transition]
Homo sapiens
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Urate is a naturally occurring product of purine metabolism and is a scavenger of biological oxidants. Uric acid readily precipitates out of aqueous solutions causing gout and kidney stones. Due to this ability, changes in urate levels are implicated in numerous disease processes. The human gene SLC22A12 encodes urate transporter 1 (URAT1), predominantly expressed in the kidney and is involved in the regulation of blood urate levels. This transport can be trans-stimulated by organic anions such as L-lactate (LACT). Defects in SLC22A12 result in idiopathic renal hypouricaemia 1 (RHUC1; MIM:220150), a disorder characterised by impaired urate reabsorption at the apical membrane of proximal renal tubule cells and high urinary urate excretion. Mutations that can cause RHUC1 include W258*, E298D, L418R, R90H and G361V (Enomoto et al. 2002, Wakida et al. 2005, Ichida et al. 2008).

Literature References
PubMed ID Title Journal Year
15634722 Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia

Kikuchi, Y, Kitamura, K, Ueda, O, Tazawa, M, Otagiri, M, Nonoguchi, H, Miyoshi, T, Kurihara, S, Matsuo, H, Oda, T, Wakida, N, Yoneta, Y, Endou, H, Adachi, M, Tomita, K, Hosoyamada, M, Oka, T, Tuyen, DG, Shimada, H

J Clin Endocrinol Metab 2005
18492088 Age and origin of the G774A mutation in SLC22A12 causing renal hypouricemia in Japanese

Kamitsuji, S, Shibasaki, T, Hosoyamada, M, Hosoya, T, Ichida, K, Kamatani, N, Hisatome, I

Clin. Genet. 2008
12024214 Molecular identification of a renal urate anion exchanger that regulates blood urate levels

Kikuchi, Y, Shimokata, K, Cha, SH, Chairoungdua, A, Igarashi, T, Shigeta, Y, Ichida, K, Kanai, Y, Hosoya, T, Oda, T, Matsuo, H, Takeda, M, Kimura, H, Enomoto, A, Endou, H, Jutabha, P, Niwa, T, Hosoyamada, M, Sekine, T

Nature 2002
Catalyst Activity

urate transmembrane transporter activity of SLC22A12 mutants [plasma membrane]

Normal reaction
Functional status

Loss of function of SLC22A12 mutants [plasma membrane]

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