NPT4, a new microsomal phosphate transporter: Mutation analysis in glycogen storage disease type Ic

Abstract

Deficiency of a microsomal phosphate transporter in the liver has been suggested in some patients affected by glycogen storage disease type Ic (GSD Ic). Several Na(+)/phosphate co-transporters have been characterized as members of the anion-cation symporter family. Recently, the cDNA sequence of two phosphate transporters, NPT3 and NPT4, expressed in liver, kidney and intestine, has been determined. We studied expression of human NPT4 in COS cells and observed an ER localization of the transporter by immunofluorescence microscopy. We speculated that this transporter could play a role in the regulation of the glucose-6-phosphatase (G6-Pase) complex. We revealed the genomic structure of NPT4 and analysed the gene as a candidate for GSD Ic. DNA was collected from five patients without mutations in G6-Pase or the G6-P transporter gene. DNA analysis of NPT4 revealed that one patient was heterozygous for a G>A transition at nucleotide 601 which would result in a G201R substitution. Our results do not confirm the hypothesis that this gene is mutated in GSD Ic patients. However, we cannot exclude that the mutation found reduces the phosphate transport efficiency, possibly modulating the G6-Pase complex.

Functional Analysis of Human Sodium-Phosphate Transporter 4 (NPT4/SLC17A3) Polymorphisms

“…In the same way, functionally relevant hNPT4 variations shown in this study may explain some of the inter-individual variations in susceptibility to certain diseases like gout (13) and glycogen storage disease type Ic (14) observed in the individuals with altered hNPT4 function.…”

Recent advances in renal urate transport: characterization of candidate transporters indicated by genome-wide association studies

“…The difference lies in the presence of the fourth exon present only in hNPT4_L. It was previously reported that NPT4 (U90545, corresponding to short isoform) shows intracellular localization when expressed in COS cells [43] but there is no data about its long form. Recently, we found that the long isoform of hNPT4 (hNPT4_L), expressed in the plasma membrane of Xenopus oocytes, mediates lowaffinity transport of organic anions such as PAH, estrone sulfate and urate in a voltage-sensitive manner, indicating that NPT4 may be involved in the apical efflux pathway for organic anions including urate [44].…”

High Dietary Inorganic Phosphate Increases Lung Tumorigenesis and Alters Akt Signaling

“…NPTs are subdivided into three families based, in part, on tissue specificity (3). These families differ by their affinity for Pi, distribution in the body, and by the mechanisms that control their activity (4,5). Among them, the NPT-2b is expressed at the apical domain of enterocytes in the small intestine, lung, testis, and mammary gland (6,7).…”