rs4246215

This is a regulatory region variant variant in the FEN1 gene.

▶

GWAS Catalog Trait Associations (63)

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

cholesterol to total lipids in medium LDL percentage

Zoodsma M et al. “A genetic map of human metabolism across the allele frequency spectrum.” Nature Genetics 57(10):2445-2455 (2025)
Allele T
OR 0.09
p 7.0e-194
N 241,027
Large GWAS
European

docosapentaenoic acid measurement

Lemaitre RN et al. “Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.” Plos Genetics 7(7):e1002193 (2011)
Allele T
OR —
β 0.070
p 1.0e-139
N 8,866
Meta-analysisMajor Consortium Study
European

alpha-linolenic acid measurement

Lemaitre RN et al. “Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.” Plos Genetics 7(7):e1002193 (2011)
Allele T
OR —
β 0.020
p 9.0e-60
N 8,866
Meta-analysisMajor Consortium Study
European

eicosapentaenoic acid measurement

Lemaitre RN et al. “Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.” Plos Genetics 7(7):e1002193 (2011)
Allele T
OR —
β 0.080
p 6.0e-55
N 8,866
Meta-analysisMajor Consortium Study
European

phospholipids:total lipids ratio

Zoodsma M et al. “A genetic map of human metabolism across the allele frequency spectrum.” Nature Genetics 57(10):2445-2455 (2025)
Allele T
OR 0.04
p 2.0e-40
N 241,027
Large GWAS
European

Red cell distribution width

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 5.0e-39
N 548,243
Major Consortium StudyLarge GWAS
multi-ancestry
▶

Research that mentions this SNP (3)

▶
A NEIL1 single nucleotide polymorphism (rs4462560) predicts the risk of radiation‐induced toxicities in esophageal cancer patients treated with definitive radiotherapy
AssociationN=187Yun Chen et al.(2013)· Cancer

A case-only study of 187 Chinese esophageal squamous cell carcinoma (ESCC) patients receiving definitive radiotherapy found that NEIL1 rs4462560 GC/CC genotypes were associated with significantly lower risk of grade ≥2 acute radiation-induced esophageal toxicity (RIET) (HR=0.421, p=0.017) and grade ≥2 radiation pneumonitis (RP) (HR=0.392, p=0.037) compared with GG genotype, but no association with overall survival. Five other SNPs in FEN1 and hOGG1 genes showed no significant associations.

Traits studied:Esophageal squamous cell carcinomaOverall survivalRadiation pneumonitis (RP)Radiation-induced esophageal toxicity (RIET)
PubMedDOIMetascience Observatory
▶
Genome-wide association study in Han Chinese identifies three novel loci for human height
Meta-analysisN=8,415Yongchen Hao et al.(2013)· Human Genetics

A meta-analysis of genome-wide association studies in 6,534 Han Chinese subjects identified three novel loci for human height at rs12612930 (ZNF638), rs11021504 (MAML2), and rs11082671 (C18orf12) reaching genome-wide significance (P < 5 × 10⁻⁸), along with confirmation of two previously reported loci (CS and CYP19A1). The study provided supporting evidence for 35 SNPs from previous GWAS and demonstrates substantial genetic overlap between Asian and European populations for this complex trait.

Traits studied:Human height
PubMedDOIMetascience Observatory
▶
FunctionalFEN1polymorphisms are associated with DNA damage levels and lung cancer risk
AssociationN=288Ming Yang et al.(2009)· Human Mutation

This cross-sectional study of 288 coke oven workers examined gene-environment interactions between FEN1 rs174538 polymorphism and polycyclic aromatic hydrocarbon (PAH) exposure, measured by urinary 1-OH-pyrene levels, on DNA damage in EGFR gene exons 19 and 21. The study found significant linear associations between PAH exposure and EGFR exon damage (P trend < 0.001 for both exons), which were modified by FEN1 rs174538 genotype—the associations were significant only in GA+AA carriers (P < 0.001) but not in GG carriers, suggesting genetic susceptibility influences PAH-induced DNA damage.

Traits studied:DNA damage (BRCA1 exon 20 damage index)DNA damage (EGFR exon 19 damage index)DNA damage (EGFR exon 21 damage index)Lung cancer riskPolycyclic aromatic hydrocarbon (PAH) exposure
PubMedDOIMetascience Observatory

About FEN1

The protein encoded by this gene removes 5' overhanging flaps in DNA repair and processes the 5' ends of Okazaki fragments in lagging strand DNA synthesis. Direct physical interaction between this protein and AP endonuclease 1 during long-patch base excision repair provides coordinated loading of the proteins onto the substrate, thus passing the substrate from one enzyme to another. The protein is a member of the XPG/RAD2 endonuclease family and is one of ten proteins essential for cell-free DNA replication. DNA secondary structure can inhibit flap processing at certain trinucleotide repeats in a length-dependent manner by concealing the 5' end of the flap that is necessary for both binding and cleavage by the protein encoded by this gene. Therefore, secondary structure can deter the protective function of this protein, leading to site-specific trinucleotide expansions. [provided by RefSeq, Jul 2008]

View all FEN1 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

Community Wiki

No community notes yet for this variant. Sign in to start one.

Comments

Sign in to join the discussion.

Loading comments…