rs1169288

This is a protein-altering variant in the HNF1A gene.

▶

GWAS Catalog Trait Associations (29)

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

interleukin-1 receptor-like 2 measurement

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)

Allele C

OR 0.14

p 9.0e-176

N 47,745

Large GWAS

European

angiotensin-converting enzyme 2 measurement

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)

Allele C

OR 0.12

p 2.0e-110

N 47,745

Large GWAS

European

Yang Z et al. “Genetic Landscape of the ACE2 Coronavirus Receptor.” Circulation 145(18):1398-1411 (2022)

Allele C

OR 0.17

p 5.0e-78

N 28,204

Large GWAS

European

Kalnapenkis A et al. “Genetic determinants of plasma protein levels in the Estonian population.” Scientific Reports 14(1):7694 (2024)

Allele C

OR 0.31

p 3.0e-8

N 497

Small GWAS

European

low density lipoprotein cholesterol measurement

Graham SE et al. “The power of genetic diversity in genome-wide association studies of lipids.” Nature 600(7890):675-679 (2021)

Allele C

OR 0.04

p 5.0e-96

N 1,320,016

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 C

OR 0.03

p 2.0e-20

N 578,944

Major Consortium StudyLarge GWAS

multi-ancestry

Klimentidis YC et al. “Phenotypic and Genetic Characterization of Lower LDL Cholesterol and Increased Type 2 Diabetes Risk in the UK Biobank.” Diabetes 69(10):2194-2205 (2020)

Allele C

OR 0.04

p 3.0e-76

N 431,167

Major Consortium StudyLarge 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 0.02

p 2.0e-26

N 416,487

Large GWAS

multi-ancestry

Klarin D et al. “Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.” Nature Genetics 50(11):1514-1523 (2018)

Allele C

OR 0.03

p 1.0e-27

N 297,626

Major Consortium StudyLarge GWAS

multi-ancestry

Kim YJ et al. “The contribution of common and rare genetic variants to variation in metabolic traits in 288,137 East Asians.” Nature Communications 13(1):6642 (2022)

Allele C

OR 0.04

p 4.0e-26

N 288,127

Large GWAS

East Asian

Spracklen CN et al. “Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.” Human Molecular Genetics 26(9):1770-1784 (2017)

Allele C

OR 0.04

p 2.0e-22

N 205,367

Large GWAS

multi-ancestry

Jee YH et al. “Genome-wide association studies in a large Korean cohort identify quantitative trait loci for 36 traits and illuminate their genetic architectures.” Nature Communications 16(1):4935 (2025)

Allele C

OR 0.03

p 6.0e-22

N 153,950

Large GWAS

East Asian

Bentley AR et al. “Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids.” Nature Genetics 51(4):636-648 (2019)

Allele C

OR 1.40

p 3.0e-12

N 125,692

Large GWAS

multi-ancestry

Teslovich TM et al. “Biological, clinical and population relevance of 95 loci for blood lipids.” Nature 466(7307):707-713 (2010)

Allele C

OR 1.42

p 1.0e-15

N 95,454

Large GWAS

European

Hoffmann TJ et al. “A large electronic-health-record-based genome-wide study of serum lipids.” Nature Genetics 50(3):401-413 (2018)

Allele C

OR —

β 0.037

p 1.0e-12

N 94,674

Large GWAS

multi-ancestry

Willer CJ et al. “Discovery and refinement of loci associated with lipid levels.” Nature Genetics 45(11):1274-1283 (2013)

Allele C

OR —

β 0.038

p 6.0e-21

N 94,595

Large GWAS

European

Lee SB et al. “Dyslipidaemia-Genotype Interactions with Nutrient Intake and Cerebro-Cardiovascular Disease.” Biomedicines 10(7) (2022)

Allele C

OR 1.27

p 1.0e-11

N 58,701

Large GWAS

East Asian

cathepsin L2 measurement

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)

Allele C

OR 0.09

p 3.0e-69

N 47,745

Large GWAS

European

non-high density lipoprotein cholesterol measurement

Graham SE et al. “The power of genetic diversity in genome-wide association studies of lipids.” Nature 600(7890):675-679 (2021)

Allele C

OR 0.03

p 2.0e-54

N 1,320,016

Large GWAS

European

urate measurement

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)

Allele C

OR 0.02

p 4.0e-24

N 394,642

Large GWAS

European

Tin A et al. “Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.” Nature Genetics 51(10):1459-1474 (2019)

Allele C

OR 0.04

p 5.0e-8

N 457,690

Large GWAS

multi-ancestry

Cho C et al. “Large-scale cross-ancestry genome-wide meta-analysis of serum urate.” Nature Communications 15(1):3441 (2024)

Allele C

OR 0.03

p 4.0e-16

N 219,768

Meta-analysisLarge GWAS

East Asian

hyperlipidemia

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 A

OR 0.05

p 1.0e-21

N 426,603

Major Consortium StudyLarge GWAS

European

metabolic disease

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 A

OR 0.05

p 3.0e-21

N 426,570

Major Consortium StudyLarge GWAS

European

HMG CoA reductase inhibitor 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 4.0e-21

N 469,111

Large GWAS

multi-ancestry

Wu Y et al. “Genome-wide association study of medication-use and associated disease in the UK Biobank.” Nature Communications 10(1):1891 (2019)

Allele C

OR 0.05

p 2.0e-15

N 290,385

Major Consortium StudyLarge GWAS

European

level of inactive C-alpha-formylglycine-generating enzyme 2 in blood

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)

Allele C

OR 0.05

p 5.0e-20

N 47,745

Large GWAS

European

▶

ClinVar annotation

Risk Factor★★★☆

17 submitters36 publications

Insulin resistance, susceptibility to; Maturity onset diabetes mellitus in young (MODY); Maturity-onset diabetes of the young type 3; Nonpapillary renal cell carcinoma; SERUM HDL CHOLESTEROL LEVEL, MODIFIER OF; Type 2 diabetes mellitus; not specified

View on ClinVar →

▶

Research that mentions this SNP (3)

▶

COX2 and NOS3 gene polymorphisms in women with gestational diabetes

ReviewMaciej Tarnowski et al.(2017)· The Journal of Gene Medicine

This comprehensive review synthesizes literature on gestational diabetes mellitus (GDM), demonstrating its complex multifactorial etiology involving genetic factors (SNPs in GCKR, KCNQ1, MTNR1B, TCF7L2), epigenetic modifications (DNA methylation and microRNA expression), and alterations in microbial composition across multiple body sites. While certain SNP variants are associated with GDM phenotypes globally, genetic predisposition alone does not explain disease development; lifestyle factors can modify epigenetic signatures and microbiota composition to modulate risk. Evidence indicates genes, epigenetic alterations, and microbiota can transfer from mother to offspring with long-term health consequences.

Traits studied:Cardiovascular diseaseFetal macrosomiaGestational diabetes mellitusHyperglycemiaHyperlipidemiaHypoglycemiaImpaired insulin secretionInflammatory conditionsInsulin resistanceMetabolic syndromeObesityPreeclampsiaType 2 diabetes

PubMed DOI Metascience Observatory

▶

Common variants in MODY genes increase the risk of gestational diabetes mellitus

AssociationN=1,880Shaat N. et al.(2006)· Diabetologia

This case-control study of 1,880 Scandinavian women (648 with gestational diabetes mellitus [GDM] and 1,232 controls) examined common variants in MODY genes. The GCK -30G→A polymorphism (rs1799884) showed increased GDM risk in an additive model (OR 1.28, 95% CI 1.06–1.53, p=0.008) and recessive model (OR 2.12, p=0.009). The HNF1A I27L polymorphism (rs1169288) showed modest increased risk with a dominant model (OR 1.31, p=0.007). Three HNF4A variants (rs2144908, rs2425637, rs1885088) were not associated with GDM risk.

Traits studied:Gestational diabetes mellitus

PubMed DOI Metascience Observatory

▶

Genetic epidemiology of MODY in the Czech republic: new mutations in the MODY genes HNF-4α, GCK and HNF-1α

AssociationN=263Pruhova S. et al.(2003)· Diabetologia

Genetic screening of 61 Czech MODY families identified 20 mutations in HNF-4α, GCK, and HNF-1α genes in 48% of families (5% MODY1, 31% MODY2, 11.5% MODY3 prevalence). Seventy percent of identified mutations were novel, including Arg125Trp and Val121Ile in HNF-4α, Glu40Lys and Gly44Asp in GCK, and Arg200Gly in HNF-1α, suggesting that most MODY mutations in this Central European population are local variants.

Traits studied:Diabetes mellitusHyperglycemiaMaturity Onset Diabetes of the Young (MODY)

PubMed DOI Metascience Observatory

About HNF1A

The protein encoded by this gene is a transcription factor required for the expression of several liver-specific genes. The encoded protein functions as a homodimer and binds to the inverted palindrome 5'-GTTAATNATTAAC-3'. Defects in this gene are a cause of maturity onset diabetes of the young type 3 (MODY3) and also can result in the appearance of hepatic adenomas. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

rs1169288

GWAS Catalog Trait Associations (29)

interleukin-1 receptor-like 2 measurement

angiotensin-converting enzyme 2 measurement

low density lipoprotein cholesterol measurement

cathepsin L2 measurement

non-high density lipoprotein cholesterol measurement

urate measurement

hyperlipidemia

metabolic disease

HMG CoA reductase inhibitor use measurement

level of inactive C-alpha-formylglycine-generating enzyme 2 in blood

ClinVar annotation

Research that mentions this SNP (3)

About HNF1A

Community Wiki

Comments