Research — GeneOps

rs7936142 Intronic variant in the primary hepatic vitamin D 25-hydroxylase gene associated with reduced CYP2R1 expression and lower circulating 25-hydroxyvitamin D concentrations

Chromosome 11 Risk Allele T Category Vitamin D Metabolism Tags Vitamin D, Vitamins, Bone Health, Immune Function, Micronutrients

The CYP2R1 gene encodes vitamin D 25-hydroxylase(), the liver enzyme responsible for the first and rate-limiting step in converting dietary or sun-derived vitamin D into the form measured in your bloodstream. Without functional CYP2R1, vitamin D cannot be converted into its bioactive metabolite, regardless of how...

rs11558538 HNMT structural variant - reduces enzyme stability and histamine clearance in tissues

Chromosome 2 Risk Allele T Category Methylation & Detox Tags Histamine, Methylation, Detoxification, Neurotransmitters

The Thr105Ile | Threonine to isoleucine at position 105 variant (rs11558538) is a well-characterized missense mutation in the HNMT gene that replaces threonine with isoleucine at position 105. Unlike the 3'UTR variant that affects how much enzyme is made, this variant changes the enzyme's structural stability and...

rs11708067 Intronic regulatory variant that reduces ADCY5 expression in pancreatic islets, impairing glucose-stimulated cAMP production and insulin secretion, and raising fasting glucose and type 2 diabetes risk

Chromosome 3 Risk Allele A Category Blood Sugar & Diabetes Tags Diabetes, Insulin, Energy Metabolism, Metabolic Health, Metabolic Syndrome, Cardiovascular

Your pancreatic beta cells have a sophisticated system for sensing blood glucose and responding with precisely calibrated insulin release. ADCY5 (adenylate cyclase 5) sits at a critical junction in this signaling chain: it converts a glucose-triggered metabolic signal into...

rs12053868 Intronic variant in IL1RAP that impairs microglial activation, accelerating brain amyloid accumulation and Alzheimer's disease progression independently of APOE status

Chromosome 3 Risk Allele G Category Neurology & Cognition Tags Alzheimer's, Neuroinflammation, Neurological Risk, Cognitive Decline, Dementia, Inflammation

The brain's immune cells — microglia — are its primary defence against accumulating amyloid-beta plaques, the toxic protein deposits that define Alzheimer's disease. To stay activated and effective, microglia rely on a molecular on-switch: the interleukin-1 signalling...

rs12251307 Intergenic variant 19 kb downstream of IL2RA associated with atopic dermatitis (OR 1.10), asthma, and type 1 diabetes risk — tags a regulatory locus controlling CD25 expression and T-regulatory cell homeostasis

Chromosome 10 Risk Allele T Category Allergy & Atopic Disease Tags Autoimmune, T-Cell Regulation, Inflammation, Type 1 Diabetes, Skin Health, Immune Function

About 19 kilobases downstream of IL2RA(https://www.ncbi.nlm.nih.gov/gene/3559), rs12251307 sits in a region of open chromatin that functions as a long-range regulatory element for the locus. IL-2 signaling through CD25 is the central survival and activation signal for regulatory T...

rs12490265 Intronic PPARG variant in a metabolic syndrome–associated haplotype block; the A allele is enriched in people without metabolic syndrome and co-segregates with the protective AGCC haplotype across the PPARG locus

Chromosome 3 Risk Allele G Category Fat Storage & Energy Tags Metabolic Syndrome, Adipogenesis, Insulin Resistance, Metabolic Health, Fat Distribution, Diabetes

PPARG (peroxisome proliferator-activated receptor gamma) is the master transcriptional regulator of adipogenesis| Adipogenesis: the process by which precursor cells differentiate into mature fat-storing adipocytes. PPARG drives expression of hundreds of genes controlling lipid storage, fatty acid uptake, and insulin...

rs1341162 Intronic CYP2C8 haplotype-tagging variant linked to altered drug metabolism capacity and bisphosphonate-related osteonecrosis of the jaw risk

Chromosome 10 Risk Allele T Category Pharmacogenomics Tags Drug Metabolism, Pharmacogenomics, Phase I, Cardiovascular, Cancer Treatment

CYP2C8 is one of the body's principal drug-processing enzymes, responsible for clearing roughly 5% of all commonly prescribed medications. Its substrates span remarkably diverse drug classes: the antidiabetics repaglinide and rosiglitazone, the chemotherapy agent paclitaxel, the antimalarial amodiaquine, and several...

rs137943601 Nonsense mutation in the LDLR gene creating a premature stop codon at position 408, abolishing LDL receptor production and causing familial hypercholesterolemia with severely elevated LDL cholesterol and early cardiovascular disease risk

Chromosome 19 Risk Allele T Category Cholesterol & Lipoproteins Tags Cholesterol, Cardiovascular, Fat Metabolism, LDL Cholesterol, Atherosclerosis, Statins

The low-density lipoprotein receptor (LDLR)(https://www.ncbi.nlm.nih.gov/gene/3949) is the central traffic controller of blood cholesterol. Every cell that needs cholesterol expresses LDLR; liver cells express the most, and it is there that the majority of circulating LDL-cholesterol is cleared from the bloodstream....

rs1554483 Intronic CLOCK variant whose G allele, in a haplotype with rs4864548 A, confers a 1.8-fold increased risk of overweight and obesity and is associated with NAFLD, metabolic syndrome in shiftworkers, and altered food-timing patterns via disrupted circadian energy regulation

Chromosome 4 Risk Allele G Category Hormones & Sleep Tags Circadian, Sleep, Obesity, Metabolic, Liver

The CLOCK gene (Circadian Locomotor Output Cycles Kaput) sits at the top of the mammalian circadian hierarchy. CLOCK protein() heterodimerizes with BMAL1 and binds E-box elements in the promoters of core clock genes including Per1, Per2, Cry1, and Cry2, generating the transcription-translation feedback loop that...

rs174561 Intronic variant in the FADS1 gene cluster that tags a haplotype block controlling delta-5 desaturase activity; the C allele reduces conversion of omega-6 and omega-3 precursors to long-chain PUFAs (AA, EPA) and also increases miR-1908-5p expression, independently lowering LDL cholesterol

Chromosome 11 Risk Allele C Category Triglycerides & Fatty Acids Tags Omega-3, Fat Metabolism, Micronutrients, Cardiovascular, LDL Cholesterol, Diet

The FADS gene cluster on chromosome 11 encodes the two rate-limiting enzymes of long-chain PUFA synthesis(). rs174561 is an intronic variant within FADS1 that tags a haplotype block governing delta-5 desaturase() activity. The C allele, which occurs in about 7% of Africans, 31% of Europeans, and over 50% of East...