rs4362

This is a synonymous variant in the ACE gene — it does not change the protein's amino acid sequence.

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GWAS Catalog Trait Associations (2)

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

angiotensin converting enzyme activity attribute

Surapaneni A et al. “Identification of 969 protein quantitative trait loci in an African American population with kidney disease attributed to hypertension.” Kidney International 102(5):1167-1177 (2022)
Allele C
OR 0.64
p 2.0e-26
N 466
Small GWAS
African American or Afro-Caribbean

X-14208--phenylalanylserine measurement

Shin SY et al. “An atlas of genetic influences on human blood metabolites.” Nature Genetics 46(6):543-550 (2014)
Allele T
OR 0.06
p 1.0e-21
N 2,455
Large GWAS
European
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ClinVar annotation

Likely Benign★★★☆
8 submitters2 publications

Hemorrhage, intracerebral, susceptibility to (ICH); Microvascular complications of diabetes, susceptibility to, 3; Renal tubular dysgenesis; Renal tubular dysgenesis of genetic origin; not specified

View on ClinVar →
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Research that mentions this SNP (3)

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Associations of polymorphisms in the genes of FGFR2, FGF1, and RBFOX2 with breast cancer risk by estrogen/progesterone receptor status
AssociationN=2,416Yu‐Ling Cen et al.(2013)· Molecular Carcinogenesis

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

Traits studied:Breast cancerBreast cancer riskER+/PR+ breast cancerER/PR negative breast cancerTriple negative breast cancer
PubMedDOIMetascience Observatory
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The role ofECE1variants in cognitive ability in old age and Alzheimer's disease risk
AssociationN=6,065Gillian Hamilton et al.(2012)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

This study evaluated variants in seven amyloid-beta degrading genes (ACE, ECE1, ECE2, IDE, MME, PLAU, TF) for association with Alzheimer's disease (AD) risk and cognitive phenotypes in older adults. In the GERAD1 cohort (3,333 AD cases, 1,225 controls), a four-SNP ECE1 intragenic haplotype (rs212524/rs212525/rs2282714/rs212531) was significantly associated with increased AD risk (OR=1.61, P=0.00035) in APOE ε4 carriers. In the Lothian Birth Cohort 1936 (LBC1936), a two-SNP ECE1 haplotype (rs2282715/rs3026883) was associated with lower non-verbal reasoning scores (β=-0.19, P=0.00036) in APOE ε4 non-carriers. Meta-analysis of four cognitive cohorts confirmed ECE1 promoter region SNPs associated with non-verbal reasoning in APOE ε4 non-carriers. Functional analysis showed the ECE1 rs213045 (338C>A) variant affected promoter activity in neuroblastoma cell lines, suggesting tissue-specific regulation.

Traits studied:Alzheimer's diseaseCognitive abilityLogical memoryMatrix reasoningNon-verbal reasoningVerbal fluency
PubMedDOIMetascience Observatory
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Genome-wide Analysis of Genetic Loci Associated With Alzheimer Disease
AssociationN=35,000Seshadri S. et al.(2010)· JAMA

This 3-stage genome-wide association meta-analysis study identified 5 novel and confirmed loci associated with late-onset Alzheimer's disease across over 35,000 individuals. The study discovered two new genome-wide significant loci: rs744373 in BIN1 (OR 1.13, p=1.59×10⁻¹¹) and rs597668 near EXOC3L2 (OR 1.18, p=6.45×10⁻⁹), and confirmed three previously reported loci in APOE (OR 2.53, p=1.04×10⁻²⁹⁵), CLU (OR 0.85, p=1.62×10⁻¹⁶), and PICALM (OR 0.89, p=3.16×10⁻¹²). These findings were validated in an independent Spanish replication sample of 2,349 individuals.

Traits studied:Alzheimer's diseaseLate-onset Alzheimer's disease
PubMedDOIMetascience Observatory

About ACE

This gene encodes an enzyme involved in blood pressure regulation and electrolyte balance. It catalyzes the conversion of angiotensin I into a physiologically active peptide angiotensin II. Angiotensin II is a potent vasopressor and aldosterone-stimulating peptide that controls blood pressure and fluid-electrolyte balance. This angiotensin converting enzyme (ACE) also inactivates the vasodilator protein, bradykinin. Accordingly, the encoded enzyme increases blood pressure and is a drug target of ACE inhibitors, which are often prescribed to reduce blood pressure. This enzyme additionally plays a role in fertility through its ability to cleave and release GPI-anchored membrane proteins in spermatozoa. Many studies have associated the presence or absence of a 287 bp Alu repeat element in this gene with the levels of circulating enzyme. This polymorphism, as well as mutations in this gene, have been implicated in a wide variety of diseases including cardiovascular pathophysiologies, psoriasis, renal disease, stroke, and Alzheimer's disease. Regulation of the homologous ACE2 gene may be involved in progression of disease caused by several human coronaviruses, including SARS-CoV and SARS-CoV-2. Alternative splicing results in multiple transcript variants encoding both somatic (sACE) and male-specific testicular (tACE) isoforms. [provided by RefSeq, Sep 2020]

View all ACE variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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