rs2631367

This is a regulatory region variant variant in the SLC22A5 gene.

GWAS Catalog Trait Associations (27)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

leukocyte quantity

Sakaue S et al. A cross-population atlas of genetic associations for 220 human phenotypes. Nature Genetics 53(10):1415-1424 (2021)
Allele G
OR 0.03
p 3.0e-42
N 504,825
Large GWAS
multi-ancestry
Vuckovic D et al. The Polygenic and Monogenic Basis of Blood Traits and Diseases. Cell 182(5):1214-1231.e11 (2020)
Allele G
OR 0.03
p 2.0e-40
N 408,112
Large GWAS
European

monocyte count

Allele G
OR
p 6.0e-31
N 639,696
Large GWAS
multi-ancestry
Vuckovic D et al. The Polygenic and Monogenic Basis of Blood Traits and Diseases. Cell 182(5):1214-1231.e11 (2020)
Allele G
OR 0.02
p 5.0e-25
N 408,112
Large GWAS
European
Verma A et al. Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele G
OR 0.04
p 2.0e-27
N 259,625
Major Consortium StudyLarge GWAS
European

neutrophil count

Sakaue S et al. A cross-population atlas of genetic associations for 220 human phenotypes. Nature Genetics 53(10):1415-1424 (2021)
Allele G
OR 0.02
p 3.0e-24
N 432,666
Large GWAS
multi-ancestry

P-Selectin measurement

Allele G
OR 0.05
p 6.0e-24
N 47,745
Large GWAS
European

lean body mass

Harris BHL et al. New role of fat-free mass in cancer risk linked with genetic predisposition. Scientific Reports 14(1):7270 (2024)
Allele G
OR 0.01
p 3.0e-21
N 337,739
Large GWAS
European

pyruvate measurement

Allele C
OR 0.04
p 5.0e-21
N 88,069
Large GWAS
European
Allele C
OR 0.04
p 5.0e-19
N 114,749
Large GWAS
European

level of CCN family member 2 in blood

Allele G
OR 0.05
p 2.0e-19
N 47,745
Large GWAS
European

palmitoylcarnitine measurement

Allele G
OR 0.12
p 4.0e-16
N 8,256
Large GWAS
European

ClinVar annotation

Benign★★★
1 submitter5 publications

Renal carnitine transport defect (CDSP)

View on ClinVar →

Research that mentions this SNP (9)

Genetic variants in the JAK1 gene confer higher risk of Behcet’s disease with ocular involvement in Han Chinese
AssociationN=2,611Shengping Hou et al.(2013)· Human Genetics

Two-stage case-control association study in 738 Han Chinese Behcet's disease patients with ocular involvement and 1,873 controls identified three JAK1 SNPs (rs2780815, rs310241, rs3790532) significantly associated with disease susceptibility (Pc=0.030-1.90×10⁻⁴) with population attributable risks of 35.0%, 28.0%, and 27.0% respectively. No significant associations were found for SLC22A4, SLC22A5, or RUNX1 polymorphisms.

Traits studied:Behcet's disease with ocular involvement
Contribution of higher risk genes and European admixture to Crohnʼs disease in African Americans
AssociationN=708Ming-Hsi Wang et al.(2012)· Inflammatory Bowel Diseases

Study of 354 African American Crohn's disease cases and 354 controls examined the contribution of European admixture and major established CD risk genes. Mean European ancestry was similar between cases (20.9%) and controls (20.4%, p=0.58). Significant associations were found with NOD2 carrier status (OR 3.28, p=0.007), ATG16L1 Thr300Ala (p=0.003), IBD5 locus genes SLC22A4 L503F (p=0.05) and SLC22A5 g-207c (p=0.03), and IL23R rs2201841 (p=0.03), but not IRGM variants.

Traits studied:Crohn's disease
Confirmation of three inflammatory bowel disease susceptibility loci in a Chinese cohort
AssociationN=147Chaolan Lv et al.(2012)· International Journal of Colorectal Disease

This case-control study in a Chinese Han population evaluated eight IBD susceptibility loci previously identified in European GWAS. The study found that NOD2 P268S contributed to Crohn's disease susceptibility (P=0.025), IL23R rs11805303 conferred protective effect against ulcerative colitis (P=0.010), and PTPN2 rs2542151 was associated with increased UC risk (P=0.001). Phenotype-genotype analysis showed P268S was associated with early-onset disease and ileal involvement in CD patients.

Traits studied:Crohn's diseaseInflammatory bowel diseaseUlcerative colitis
Two independent genetic factors responsible for the associations of the IBD5 locus with Crohnʼs disease in the Czech population
AssociationN=939Ondrej Hradsky et al.(2011)· Inflammatory Bowel Diseases

This case-control study in 469 Czech Crohn's disease (CD) patients and 470 controls examined the IBD5 locus, identifying two independent genetic factors: rs6596075 (OR=0.70, protective allele G, p=0.018 in dominant model) and the haplotype tagged by rs2188962 and IGR2063b_1 (OR=1.38 for IGR2063b_1, p=0.00075 in log-additive model). The study demonstrates that these two genetic factors independently contribute to CD susceptibility at the IBD5 locus.

Traits studied:Crohn's disease
IGR2096a_1 T and IGR2198a_1 C alleles on IBD5 locus of chromosome 5q31 region confer risk for Crohn’s disease in Hungarian patients
AssociationN=759Lilla Lakner et al.(2009)· International Journal of Colorectal Disease

A case-control study of 217 Crohn's disease, 252 ulcerative colitis, and 290 control patients in Hungary examining associations with IBD5 locus variants. The IGR2096a_1 T allele (rs12521868) and IGR2198a_1 C allele (rs11739135) showed significantly increased frequencies in Crohn's disease (47.2% and 45.9% vs 38.2% and 37.7% in controls, p<0.05) and were independent risk factors (OR=1.748, 95% CI 1.186-2.574 for T allele; OR=1.646, 95% CI 1.119-2.423 for C allele), while SLC22A4 C1672T and SLC22A5 G-207C variants showed no association.

Traits studied:Crohn's diseaseInflammatory bowel diseaseUlcerative colitis
IL4 in the 5q31 context: association studies of type 1 diabetes and rheumatoid arthritis in the Spanish population
AssociationN=1,455Nuñez C. et al.(2008)· Immunogenetics

This case-control study of 316 T1D patients, 599 RA patients, and 540 Spanish controls examined IL4 polymorphisms in the context of the 5q31-33 locus. The IL4 -590C/T polymorphism (rs2243250) showed no individual association with T1D or RA. However, stratified analysis by the OCTN1 L503F variant (rs1050152) revealed a significant association between IL4 and T1D in OCTN1-negative individuals (OR=1.95, 95% CI=1.07-3.55, p=0.02), demonstrating that linkage disequilibrium in this complex region can mask or reveal genetic effects.

Traits studied:Rheumatoid arthritisType 1 diabetes
Contributions of IBD5, IL23R, ATG16L1, and NOD2 to Crohnʼs disease risk in a population-based case-control study: Evidence of gene–gene interactions
AssociationN=646Toshihiko Okazaki et al.(2008)· Inflammatory Bowel Diseases

Population-based case-control study (213 CD cases, 315 controls) examining associations between IBD5, IL23R, ATG16L1, and NOD2 genetic variants and Crohn's disease risk. IL23R rs10889677 showed the strongest association with CD (OR=2.47, 95% CI 1.70-3.57), while rs11209026 and rs7517848 were protective (OR=0.44 and OR=0.62 respectively). ATG16L1 Thr300Ala showed strong association (homozygote OR=2.38). Evidence suggested gene-gene interactions between IBD5 and IL23R loci.

Traits studied:Crohn's diseaseInflammatory bowel diseaseUlcerative colitis
Runt-related transcription factor 3 is associated with ulcerative colitis and shows epistasis with solute carrier family 22, members 4 and 5
AssociationN=839Rinse K. Weersma et al.(2008)· Inflammatory Bowel Diseases

This genetic association study of 543 IBD patients (309 CD, 234 UC) and 296 controls found that RUNX3 SNP rs2236851 is associated with ulcerative colitis (OR 1.61, 95% CI 1.11-2.32, P=0.020), with stronger association for pancolitis (OR 1.86). SLC22A4/5 SNPs rs272893 and rs273900 are associated with Crohn's disease (OR 2.16 and 2.40, respectively). An epistatic interaction between RUNX3 and SLC22A4/5 increased UC risk (OR 3.83, P=0.018). RUNX3 mRNA expression is elevated in inflamed colonic mucosa of UC patients.

Traits studied:Crohn's diseaseInflammatory bowel diseaseUlcerative colitis
Genetic susceptibility has a more important role in pediatric-onset Crohnʼs disease than in adult-onset Crohnʼs disease
AssociationN=1,071Lissy de Ridder et al.(2007)· Inflammatory Bowel Diseases

This case-control study examined the role of CARD15, TLR4, SLC22A4/5, and DLG5 polymorphisms in 103 pediatric-onset and 696 adult-onset inflammatory bowel disease (IBD) patients compared to 272 healthy controls. CARD15 3020insC homozygosity was significantly more common in pediatric-onset Crohn's disease (CD) versus adult-onset CD (4.2% vs 0.6%, RR 7.1, 95% CI 1.2-42.0, P=0.04). SLC22A4/5 rs3792876 was significantly associated with pediatric-onset CD (6.1% vs 1.1% in adult-onset CD, P=0.02). DLG5 rs2165047 was associated with perianal disease in pediatric CD patients (RR 2.4, 95% CI 1.4-4.0, P=0.003).

Traits studied:Crohn's diseaseInflammatory bowel diseaseUlcerative colitis

About SLC22A5

Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is a plasma integral membrane protein which functions both as an organic cation transporter and as a sodium-dependent high affinity carnitine transporter. The encoded protein is involved in the active cellular uptake of carnitine. Mutations in this gene are the cause of systemic primary carnitine deficiency (CDSP), an autosomal recessive disorder manifested early in life by hypoketotic hypoglycemia and acute metabolic decompensation, and later in life by skeletal myopathy or cardiomyopathy. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]

View all SLC22A5 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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