Solute Carrier Family 22 (Organic Anion/urate Transporter), Member 12 Proteine (SLC22A12)

Mouse (Murine) Solute Carrier Family 22 (Organic Anion/urate Transporter), Member 12 (SLC22A12) Interaktionspartner

1. Urat1-Uox double knockout mice are a suitable animal model for renal hypouricemia.

2. Immunostaining and highly-sensitive in situ hybridization was used to assess the distribution of UA transporters: GLUT9/URATv1, ABCG2, and URAT1. Immunostaining for GLUT9 was observed in ependymal cells, neurons, and brain capillaries. Immunostaining for ABCG2 was observed in the choroid plexus epithelium and brain capillaries, but not in ependymal cells. These results were validated by in situ hybridization.

3. The cause of obesity/metabolic syndrome-associated hyperuricemia appears to be associated with the urate reabsorption transporter Urat1 protein enhanced by fat.

4. Although the fractional excretion of urate of knockout mice was tend to higher than that of wildtype mice, the urate reabsorption ability remained in the kidney of knockout mice, indicating a urate reabsorptive transporter other than Urat1.

5. mouse RST mediates the efflux of organic anions including urate and works as exit for organic anions in the proximal tubules

6. NHERF-1 exerts a significant effect on the renal tubular reabsorption of uric acid in the mouse by modulating the brush Border membrane abundance of mURAT1.

Human Solute Carrier Family 22 (Organic Anion/urate Transporter), Member 12 (SLC22A12) Interaktionspartner

1. Which was caused by compound heterozygous mutations of the SLC22A12 gene.

2. This is the first identification of a family with mild renal hypouricemia1 associated to the p.T467 M variant. The sequencing analysis of SLC22A12 revealed a potentially deleterious missense variant c.1400C > T (p.T467 M, rs200104135) in heterozygous state.

3. Findings provide new insights into the genetic architecture of serum urate, and highlight molecular targets in SLC22A12 and SLC2A9 for lowering serum urate and preventing gout.

4. URAT1 and GLUT9 mutations in Spanish patients with renal hypouricemia

5. The rs475688 polymorphism is associated with gout susceptibility. The correlation between rs3825016 polymorphism of SLC22A12 and hyperuricaemia susceptibility is possible. [Meta-Analysis]

6. Combined exposure to the four high-risk genotypes of ALPK1 and the uric-acid-related loci of ABCG2, SLC2A9, and SLC22A12 was associated with an increased gout risk and a high PPV for gout.

7. Human-rat transporter chimeras revealed that human URAT1 serine-35, phenylalanine-365 and isoleucine-481 are necessary and sufficient to provide up to a 100-fold increase in affinity for inhibitors. Moreover, serine-35 and phenylalanine-365 are important for high-affinity interaction with the substrate urate.

8. Immunoreactivity of URAT1 was observed on the basolateral side of the cytoplasm of epithelial cells in the choroid plexus.

9. A meta-analysis of all gout with Japanese, Caucasian and NZ Polynesian populations revealed that rs2285340 of SLC22A12 and rs1165196 of SLC17A1 showed a significant association but did not reach a genome-wide significance level.

10. The present proof-of-principle paper demonstrates that the multilocus profiles of ABCG2, SLC2A9 and SLC22A12 increase susceptibility to asymptomatic hyperuricaemia, gout and tophi.

11. The common dysfunction allelic variants of URAT1 exist in the general Roma population and thus renal hypouricemia should be kept in differential diagnostic algorithm on Roma patients with defect in renal tubular urate transport.

12. novel variants p.R92C and p.R203C associated with renal hypouricemia type 1

13. URAT1 nonfunctional variants are protective genetic factors for gout/hyperuricemia, and also demonstrated the sex-dependent effect size of these URAT1 variants on serum uric acid (P for interaction = 1.5 x 10(-12)).

14. c.1245_1253del and c.1400C>T variants present in the Czech and Slovak Roma population at unexpectedly high frequencies

15. These results suggest that URAT1 rs3825016 and rs1529909 polymorphisms influence the uricosuric action of losartan

16. Depletion of UA due to SLC22A12/URAT1 loss-of-function mutations causes endothelial dysfunction in hypouricemia patients.

17. not only loss-of-function mutation of URAT1 but also the dominant-negative effect cause RHUC through loss of UA absorption, partly due to protein misfolding caused by accumulation of URAT1 protein in the endoplasmic reticulum

18. Polymorphisms in GCKR, SLC17A1 and SLC22A12 were associated with phenotype gout in Han Chinese males.

19. protein expression of URAT1 and GLUT9 in renal tissues of patients with uric acid (UA) nephrolithiasis

20. There was no significant mutation found in SLC22A12 and SLC2A9 in this familial aggregation of Chinese female premenopausal gout.