Table 2 Gene (SNP) and function summary
Gene (Protein) | Protein Function | SNP (Class) | SNP Effect | References |
|---|---|---|---|---|
ABCG2 (ABCG2) | One of the most important UA regulatory transporter. The ATP-binding cassette transporter is responsible for urate excretion and expressed kidneys, GI tract, and liver | rs2231142 (G > T) (Missense variant) | Reduction in ABCG2 transporter activity by 50%; urate under-excretion and hyperuricemia are caused by Glu 141 Lys amino acid substitution | [34] |
SLC2A9 (GLUT9) | High-capacity urate, fructose, and glucose transporter located on both sides of the kidney’s apical and basolateral membrane. This protein is expressed in liver, kidney, and chondrocytes tissues. Also strongly associated with increase serum UA | rs734553 (G > T) (Intronic variant) | Increases risk for gout through altering urate transporter affinity | [52] |
SLC16A9 (MCT9) | Monocarboxylic acid transporter protein located in the apical side of kidneys and is responsible for urate excretion | rs2242206 (G > T) (Missense variant) | Reported to substantially increase the risk of renal overload gout with an odds ratio of 1.28 (p = 0.012) | [42] |
SLC17A1 (NPT1) | Uric acid transport protein located on the apical membrane of the renal proximal convoluted tubule and contributes to urate efflux | rs1183201(T > A) (Intronic variant) | It is known to be associated with decreased urate levels and the A allele seems to be the protective allele in the EUR population (Beta effect =  − 0.062) | [34] |
SLC22A11 (OAT4) | Organic anion transporter 4 (OAT4) is a UA transporter and is responsible for urate reabsorption through the kidney | rs17300741(G > A) (Intronic variant) | It is linked to renal under-excretion of SU in EUR descent (Beta effect = 0.062) | |
SLC22A12 (URAT1) | Urate 1 transporter (URAT1) is an important UA transporter located on the apical side of the proximal tubule and is responsible for the majority of UA reabsorption | rs505802 (C > T) (Intergenic variant) | It is associated with decreased SU levels in the EUR population. (Beta effect =  − 0.056) | [34] |
GCKR (GCKR) | Glucokinase is a regulator protein with a role in endocrine and metabolic phenotypes that may be associated with urate concentrations | rs780094 (C > T) (Intronic variant) | It is associated with glucose metabolism, lipid levels, gout risk, and SU levels (Beta effect = 0.052) | |
PDZK1 (PDZ) | It is a scaffolding protein located on the apical side of the proximal tubule in the kidney, which has a role in maintaining the balance of urate levels through the formation of urate transportome | rs12129861(C > T) (Intergenic variant) | It is associated with lower serum urate levels among people of EUR ancestry (Beta effect =  − 0.06) | |
LRRC16A (CARMIL1) | A protein expressed on the apical side of proximal tubules in the kidneys, which is known as capping protein ARP2/3 and myosin-I linker (CARMIL). This protein has a role in urate transportome formation, which mediates UA reabsorption | rs742132 (G > A) (Intronic variant) | The risk allele A is associated with increased SU in individuals of EUR descent (Beta effect = 0.054) |