rs340874

This is a upstream gene variant variant in the PROX1 gene.

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GWAS Catalog Trait Associations (9)

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

type 2 diabetes mellitus

Suzuki K et al. “Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.” Nature 627(8003):347-357 (2024)
Allele C
OR —
p 1.0e-70
N 2,535,601
Large GWAS
multi-ancestry
Elashi AA et al. “Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus.” Bmc Medical Genomics 17(1):115 (2024)
Allele C
OR 0.06
p 1.0e-30
N 6,710,881
Meta-analysisLarge GWAS
multi-ancestry
Vujkovic M et al. “Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis.” Nature Genetics 52(7):680-691 (2020)
Allele C
OR 0.05
p 6.0e-45
N 1,407,282
Meta-analysisLarge GWAS
multi-ancestry
Mahajan A et al. “Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps.” Nature Genetics 50(11):1505-1513 (2018)
Allele C
OR 1.07
p 2.0e-22
N 898,130
Large GWAS
European
Sakaue S et al. “A cross-population atlas of genetic associations for 220 human phenotypes.” Nature Genetics 53(10):1415-1424 (2021)
Allele C
OR 0.05
p 4.0e-17
N 667,504
Large GWAS
multi-ancestry
Xue A et al. “Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes.” Nature Communications 9(1):2941 (2018)
Allele C
OR 0.06
p 8.0e-18
N 659,316
Large GWAS
multi-ancestry
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 C
OR 0.04
p 1.0e-16
N 612,947
Major Consortium StudyLarge GWAS
multi-ancestry
Huerta-Chagoya A et al. “Rare variant analyses in 51,256 type 2 diabetes cases and 370,487 controls reveal the pathogenicity spectrum of monogenic diabetes genes.” Nature Genetics 56(11):2370-2379 (2024)
Allele C
OR 0.08
p 4.0e-27
N 421,743
Large GWAS
multi-ancestry
Mahajan A et al. “Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation.” Nature Genetics 54(5):560-572 (2022)
Allele C
OR 0.06
p 1.0e-18
N 251,740
Large GWAS
European
Zhao W et al. “Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease.” Nature Genetics 49(10):1450-1457 (2017)
Allele C
OR 0.05
p 6.0e-10
N 183,651
Large GWAS
multi-ancestry

glucose measurement

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 T
OR 0.03
p 1.0e-32
N 601,780
Major Consortium StudyLarge GWAS
multi-ancestry

blood glucose amount

Lagou V et al. “Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.” Nature Communications 12(1):24 (2021)
Allele C
OR 0.02
p 1.0e-15
N 140,595
Large GWAS
European
Dupuis J et al. “New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.” Nature Genetics 42(2):105-116 (2010)
Allele C
OR 0.01
p 7.0e-12
N 46,186
Large GWAS
European

diabetic neuropathy

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 T
OR 0.05
p 5.0e-13
N 614,793
Major Consortium StudyLarge GWAS
multi-ancestry

diabetic retinopathy

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 T
OR 0.06
p 5.0e-12
N 432,209
Major Consortium StudyLarge GWAS
European

Drugs used in diabetes use measurement

Sakaue S et al. “A cross-population atlas of genetic associations for 220 human phenotypes.” Nature Genetics 53(10):1415-1424 (2021)
Allele C
OR 0.05
p 2.0e-10
N 484,639
Large GWAS
multi-ancestry

psoriasis, type 2 diabetes mellitus

Patrick MT et al. “Causal Relationship and Shared Genetic Loci between Psoriasis and Type 2 Diabetes through Trans-Disease Meta-Analysis.” The Journal of Investigative Dermatology 141(6):1493-1502 (2021)
Allele C
OR 1.06
p 3.0e-8
N 925,490
Meta-analysisLarge GWAS
European

diabetes mellitus

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 T
OR 0.05
p 2.0e-15
N 404,034
Major Consortium StudyLarge GWAS
multi-ancestry
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Research that mentions this SNP (5)

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A Diabetes-Associated Genetic Variant is Associated with Diastolic Dysfunction and Cardiovascular Disease
AssociationN=15,215John Molvin et al.(2020)· ESC Heart Failure

This association study examined 43 diabetes-related SNPs in relation to diastolic dysfunction and cardiovascular disease across two Swedish cohorts. HNF1B rs757210 (T-allele) was the main finding, associated with prevalent diastolic dysfunction in both the discovery cohort (MPP-RES; OR 1.21, P=0.024) and replication cohort (VARA; OR 1.38, P=0.042), and with increased risk of incident CVD (HR 1.05, P=0.042) but not CHF over 30+ years of follow-up.

Traits studied:Cardiovascular diseaseCongestive heart failureDiastolic dysfunctionType 2 diabetes
PubMedDOIMetascience Observatory
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Transethnic insight into the genetics of glycaemic traits: fine-mapping results from the Population Architecture using Genomics and Epidemiology (PAGE) consortium
AssociationN=26,760Stephanie A. Bien et al.(2017)· Diabetologia

Transethnic fine-mapping study of glycaemic traits in 26,760 participants (Hispanic/Latino, African, Asian, and Native American) using the Metabochip. Replicated 31/39 fasting glucose and 14/17 fasting insulin loci from European GWAS. Identified two novel secondary signals at G6PC2-rs477224 and GCK-rs2908290, a population-specific signal at G6PC2-rs77719485 in African ancestry, and one novel locus at SLC17A2-rs75862513 for fasting insulin.

Traits studied:Fasting glucoseFasting insulinType 2 diabetes
PubMedDOIMetascience Observatory
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PROX1 Gene Variant is Associated with Fasting Glucose Change After Antihypertensive Treatment
AssociationN=456Yan Gong et al.(2014)· Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy

A pharmacogenomics study of 456 hypertensive participants examining whether fasting glucose GWAS variants predict glucose response to antihypertensive medications. The primary finding was that PROX1 rs340874 (C allele) was significantly associated with greater glucose elevation after 9 weeks of atenolol monotherapy (p=0.0013, beta = +2.39 mg/dL per allele). Two additional SNPs showed nominal associations: ARAP1 rs11603334 with atenolol response and SLC2A2 rs11920090 with HCTZ response.

Traits studied:Atenolol-induced hyperglycemiaFasting glucoseGlucose response to antihypertensive drugsHydrochlorothiazide-induced hyperglycemiaHypertension
PubMedDOIMetascience Observatory
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Identification of CpG-SNPs associated with type 2 diabetes and differential DNA methylation in human pancreatic islets
AssociationN=84Dayeh TA et al.(2013)· Diabetologia

Of 40 SNPs previously associated with type 2 diabetes, 19 (48%) introduce or remove CpG sites. In 84 human pancreatic islet donors, all 16 analyzed CpG-SNPs showed statistically significant differential DNA methylation (p≤2.3×10⁻⁵). Several CpG-SNPs including rs391300 (SRR), rs5945326 (DUSP9), rs11708067 (ADCY5), rs5015480 (HHEX), rs13266634 (SLC30A8), rs1801214 (WFS1), rs564398 (CDKN2A), and rs2237895 (KCNQ1) were associated with differential gene expression, alternative splicing, or hormone secretion, suggesting DNA methylation-mediated mechanisms linking genetic variants to type 2 diabetes pathogenesis.

Traits studied:Glucagon secretionInsulin contentInsulin secretionType 2 diabetes
PubMedDOIMetascience Observatory
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Type 2 diabetes risk alleles near ADCY5, CDKAL1 and HHEX-IDE are associated with reduced birthweight
AssociationN=4,213Andersson EA et al.(2010)· Diabetologia

This association study of 4,213 Danish individuals examined 25 type 2 diabetes risk variants and their association with birthweight. The study found that type 2 diabetes risk alleles near ADCY5 (rs11708067, β = -33 g, p = 0.004), CDKAL1 (rs7756992, β = -22 g, p = 0.04), and HHEX-IDE (rs1111875, β = -16 g in meta-analysis, p = 8×10⁻⁵, n = 25,164) were associated with reduced birthweight, supporting the fetal insulin hypothesis. Meta-analyses confirmed these associations and showed no strong general effect on birthweight from the 25 common type 2 diabetes risk alleles combined.

Traits studied:Birth lengthBirthweightPonderal indexType 2 diabetes
PubMedDOIMetascience Observatory

About PROX1

The protein encoded by this gene is a member of the homeobox transcription factor family. Members of this family contain a homeobox domain that consists of a 60-amino acid helix-turn-helix structure that binds DNA and RNA. The protein encoded by this gene is conserved across vertebrates and may play an essential role during development. Altered levels of this protein have been reported in cancers of different organs, such as colon, brain, blood, breast, pancreas, liver and esophagus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

View all PROX1 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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