Uric Acid & Kidney Function

Missense variant in SLC17A1 (NPT1) encoding a Thr269Ile substitution; the G allele (Thr269) is a gain-of-function variant that enhances renal NPT1-mediated urate secretion and lowers gout risk, while the common A allele (Ile269) carries baseline NPT1 activity and higher gout susceptibility

Missense variant in the innate immune kinase ALPK1 (Met861Thr); the C allele is associated with elevated gout risk in East Asian populations through altered URAT1-mediated urate homeostasis and NF-κB inflammatory signaling

Nonsense mutation in URAT1 that abolishes urate reabsorption in the kidney, causing renal hypouricemia type 1 with very low serum uric acid and risk of exercise-induced acute kidney injury

Intergenic variant in the SLC2A9 urate-transporter locus — the C allele is associated with lower serum uric acid levels and reduced gout risk

Uromodulin promoter variant — strongest GWAS signal for chronic kidney disease risk, affecting salt handling and blood pressure via NKCC2

Intronic variant in the carbonic anhydrase 1 gene cluster on chromosome 8 associated with blood zinc levels in genome-wide association studies; CA1 is a zinc-binding metalloenzyme expressed at very high levels in erythrocytes

Missense variant in the GLUT9 renal urate transporter; the T allele (Val→Ile substitution) reduces urate reabsorption in the proximal tubule, lowering serum uric acid and conferring protection against hyperuricemia and gout

Intronic variant in the OAT4 renal urate transporter that modulates uric acid reabsorption in the proximal tubule, with the C allele raising serum urate and increasing gout risk especially in diuretic users

Synonymous coding variant in the URAT1 renal urate transporter; the C allele is associated with increased urate reabsorption and 27% higher odds of hyperuricemia, completing the URAT1 genetic panel alongside rs505802 (promoter) and rs121907892 (W258X)

UMOD promoter variant affecting uromodulin expression, linked to CKD, salt-sensitive hypertension, and gout risk with paradoxical kidney stone protection

Intronic regulatory variant in the URAT1 renal urate transporter gene; the T allele upregulates SLC22A12 expression, increasing urate reabsorption and raising serum uric acid, with TT individuals at substantially higher gout risk

Upstream regulatory variant in the URAT1 urate reabsorption transporter gene; the C allele increases SLC22A12 expression and renal urate reabsorption, elevating serum uric acid and gout risk, with the strongest effects in East Asian and African populations where the C allele predominates

Intronic variant in the UGT1A gene cluster (chromosome 2q37) strongly associated with serum bilirubin levels; the T allele reduces glucuronidation capacity, causing mild hyperbilirubinemia and a dose-dependent increase in pigment gallstone risk

Intronic variant in PRKG2 (cGMP-dependent protein kinase II); the T allele was associated with gout susceptibility in a recessive model in a Taiwanese population, though a Japanese replication study found no association

Rare pathogenic missense variant in the UGT1A1 gene that severely reduces bilirubin glucuronidation; homozygotes develop Crigler-Najjar syndrome type II with persistent unconjugated hyperbilirubinemia that responds to phenobarbital treatment

Protective missense modifier in APOL1 that abolishes G2 risk allele cytotoxicity, strongly reducing kidney disease risk in carriers of G2-containing high-risk genotypes

Intronic regulatory variant physically located in PDILT that controls uromodulin (Tamm-Horsfall protein / UMOD) expression — the strongest genetic predictor of longitudinal kidney function decline in the general population. Catalog gene attribution is UMOD (the regulatory target and clinically relevant gene); physical location is PDILT (adjacent gene in the same LD block).