rs2274223
This is a variant in the PLCE1 gene that changes a histidine to an arginine.
▶GWAS Catalog Trait Associations (2)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (2)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
esophageal carcinoma
esophageal squamous cell carcinoma
▶ClinVar annotation
Focal segmental glomerulosclerosis (FSGS); Nephrotic syndrome, type 3 (NPHS3); not specified
View on ClinVar →▶Research that mentions this SNP (9)
▶Predictive model for risk of gastric cancer using genetic variants from genome‐wide association studies and high‐evidence meta‐analysisAssociationN=2,287Lixin Qiu et al.(2020)· Cancer Medicine
This case-control study of 1,115 gastric cancer cases and 1,172 Eastern Chinese controls identified six SNPs (rs13361707, rs2294008, rs4072037, rs3762272, rs2274223, rs80142782) associated with increased gastric cancer risk with ORs ranging from 1.19–1.47. A predictive model combining these genetic variants with BMI achieved an AUC of 0.684 compared to 0.653 for BMI alone, and revealed a gene-environment interaction between low BMI and genetic risk variants.
▶G‐A variant in miR‐200c binding site of EFNA1 alters susceptibility to gastric cancerMethodsN=5,542Yingfei Li et al.(2014)· Molecular Carcinogenesis
Pathway analysis of a gastric cancer GWAS dataset using ICSNPathway identified 7 candidate SNPs (rs4745, rs12904, rs1801019, rs364897, rs11187870, rs2274223, rs3765524) in 4 genes (EFNA1, UMPS, GBA, PLCE1) and 12 biological pathways. Four hypothetical mechanisms were proposed: ephrin receptor binding via EFNA1, pyrimidine metabolism via UMPS, cyanoamino acid metabolism via GBA, and cell growth/lipid biosynthesis via PLCE1.
▶Genetic variants at 4q21, 4q23 and 12q24 are associated with esophageal squamous cell carcinoma risk in a Chinese populationAssociationN=4,412Yong Gao et al.(2013)· Human Genetics
A case-control study of 2,139 esophageal squamous cell carcinoma (ESCC) cases and 2,273 controls in a Chinese population examined six SNPs previously associated with upper aerodigestive tract cancers in Europeans. Four SNPs showed significant association with ESCC risk: rs1494961 at 4q21 (OR=1.15, 95% CI=1.05-1.26), rs1229984 in ADH1B at 4q23 (OR=1.24, 95% CI=1.13-1.36), rs1789924 near ADH1C at 4q23 (OR=1.20, 95% CI=1.03-1.39), and rs671 in ALDH2 at 12q24 (OR=0.83, 95% CI=0.75-0.91). Combined analysis showed significant allele-dosage effects with individuals carrying 5+ risk alleles having 1.76-fold increased ESCC risk.
▶A sequence variant in the phospholipase C epsilon C2 domain is associated with esophageal carcinoma and esophagitisAssociationN=10,672Li‐Dong Wang et al.(2013)· Molecular Carcinogenesis
The PLCE1 A5780G variant (rs2274223, His1927Arg) is associated with increased esophageal cancer and esophagitis risk. The G allele is linked to elevated PLCE1 mRNA, protein, and enzyme activity in cancer cells and tissues. In 10,614 Chinese subjects, the G allele showed significant association with moderate-to-severe esophagitis in high-incidence cancer areas (OR 6.03, 95% CI 1.59-22.9, P=0.008) but not in low-incidence areas (OR 0.74, 95% CI 0.33-1.64).
▶Polymorphisms in prostate stem cell antigen gene rs2294008 increase gastric cancer risk in ChineseAssociationN=1,466Zhirong Zeng et al.(2011)· Molecular Carcinogenesis
Case-control study of 692 stomach cancer cases and 774 controls in a Chinese population found significant associations between four GWAS-identified SNPs and gastric cancer susceptibility: PSCA rs2294008 (OR=1.37, 95% CI=1.07-1.74), PSCA rs2976392 (OR=1.30, 95% CI=1.02-1.65), and PLCE1 rs2274223 (OR=1.48, 95% CI=1.15-1.90) increased risk, while MUC1 rs4072037 (OR=0.77, 95% CI=0.60-0.98) was protective. Subjects carrying 2-4 risk genotypes had significantly increased stomach cancer risk (OR=1.30, 95% CI=1.03-1.64).
▶Association of a common genetic variant in prostate stem‐cell antigen with gastric cancer susceptibility in a Korean populationAssociationN=1,466Hye‐Rim Song et al.(2011)· Molecular Carcinogenesis
A case-control study of 692 stomach cancer cases and 774 controls in a Han Chinese population examined associations of four GWAS-identified SNPs with gastric cancer susceptibility. PSCA rs2294008 (CT: OR=1.37, 95% CI=1.07-1.74), PSCA rs2976392 (AG: OR=1.30, 95% CI=1.02-1.65), and PLCE1 rs2274223 (AG: OR=1.48, 95% CI=1.15-1.90) were all significantly associated with increased stomach cancer risk, while MUC1 rs4072037 (CT: OR=0.77, 95% CI=0.60-0.98) was protective. Carriers of multiple risk genotypes had significantly elevated cancer risk.
▶Genetic variant in PSCA predicts survival of diffuse‐type gastric cancer in a Chinese populationReviewMeilin Wang et al.(2011)· International Journal of Cancer
Letter to the editor discussing peritoneal carcinomatosis from gastric cancer management and genetic susceptibility. Authors discuss GWAS findings including PSCA variants rs2976392 and rs2294008 at 8q24 associated with diffuse-type gastric cancer in Asian populations, and SNPs at 1q22 (rs4072037) and 10q23 (rs2274223) associated with gastric cancer risk in Chinese populations. The letter emphasizes the need for prospective randomized trials and future GWAS studies to identify novel genetic loci for peritoneal metastasis susceptibility.
▶Genetic variation of PSCA gene is associated with the risk of both diffuse‐ and intestinal‐type gastric cancer in a Chinese populationAssociationN=1,466Yan Lu et al.(2010)· International Journal of Cancer
Case-control study of 692 stomach cancer cases and 774 controls in Han Chinese examining associations between four GWAS-identified SNPs and gastric cancer risk. PSCA rs2294008 (OR=1.37), rs2976392 (OR=1.30), and PLCE1 rs2274223 (OR=1.48) showed increased risk, while MUC1 rs4072037 was protective (OR=0.77). Combined risk genotypes increased cancer susceptibility.
▶Association of prostate stem cell antigen gene polymorphisms with the risk of stomach cancer in JapaneseAssociationN=1,466Keitaro Matsuo et al.(2009)· International Journal of Cancer
Case-control study (692 cases, 774 controls) in Han Chinese population examining associations of four GWAS-identified SNPs with stomach cancer risk. PSCA rs2294008 (CT vs CC: OR=1.37, 95% CI=1.07-1.74), PSCA rs2976392 (AG vs GG: OR=1.30, 95% CI=1.02-1.65), and PLCE1 rs2274223 (AG vs AA: OR=1.48, 95% CI=1.15-1.90) were associated with increased stomach cancer risk, while MUC1 rs4072037 (CT vs TT: OR=0.77, 95% CI=0.60-0.98) was protective.
About PLCE1
This gene encodes a phospholipase enzyme that catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate to generate two second messengers: inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). These second messengers subsequently regulate various processes affecting cell growth, differentiation, and gene expression. This enzyme is regulated by small monomeric GTPases of the Ras and Rho families and by heterotrimeric G proteins. In addition to its phospholipase C catalytic activity, this enzyme has an N-terminal domain with guanine nucleotide exchange (GEF) activity. Mutations in this gene cause early-onset nephrotic syndrome; characterized by proteinuria, edema, and diffuse mesangial sclerosis or focal and segmental glomerulosclerosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Sep 2009]
View all PLCE1 variants →Gene information from NCBI Gene. Variant classifications from ClinVar.
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