Research — GeneOps

rs10918594 Regulatory variant upstream of NOS1AP (CAPON) associated with QT interval prolongation via altered nNOS-mediated cardiac repolarization; the G allele extends QTc by ~3.6 ms per copy

Chromosome 1 Risk Allele G Category Arrhythmia & Heart Rhythm Tags Arrhythmia, Cardiovascular, Heart Disease, Nitric Oxide, Blood Pressure

The QT interval(https://pubmed.ncbi.nlm.nih.gov/17576865/) is one of medicine's most important cardiac biomarkers. A prolonged QTc interval predisposes to torsades de pointes(https://pubmed.ncbi.nlm.nih.gov/19643915/). Genetics account for roughly 30% of QTc variation in the population — and the NOS1AP gene harbors...

rs11220465 Common intronic variant in the ST3GAL4 sialyltransferase gene associated with modestly elevated VWF antigen and Factor VIII activity levels; the A allele impairs sialic acid capping of these clotting proteins, slowing their hepatic clearance and raising plasma concentrations

Chromosome 11 Risk Allele A Category Coronary Artery Disease & Atherosclerosis Tags Blood Clotting, Thrombophilia, Cardiovascular, Thrombosis, Fibrinolysis

Every protein in your blood has a molecular expiration date stamped on its surface as a sugar code. Von Willebrand factor (VWF)(https://pubmed.ncbi.nlm.nih.gov/33570640/) and Factor VIII (FVIII)(https://pubmed.ncbi.nlm.nih.gov/30471183/) both carry a coating of sialic acid residues on their glycan chains. When these...

rs11235972 Intronic UCP3 variant associated with skeletal muscle fat oxidation capacity, hand grip strength, and survival in aging populations

Chromosome 11 Risk Allele A Category Liver Fat Tags Fat Metabolism, Mitochondria, Muscle, Energy Metabolism, Aging, Oxidative Stress

UCP3 (uncoupling protein 3)(https://pubmed.ncbi.nlm.nih.gov/16384603/) has long been debated as a thermogenic protein. The current consensus, however, points to a different primary role: protecting skeletal muscle mitochondria from the toxic accumulation of excess fatty acids. rs11235972 is an intronic variant in...

rs113994167 Most common VLCAD deficiency variant in the US, causing mild late-onset disease with exercise-induced rhabdomyolysis and fasting intolerance due to partial loss of mitochondrial fatty acid oxidation

Chromosome 17 Risk Allele C Category Metabolic Enzymes & Rare Disorders Tags Fat Metabolism, Mitochondria, Metabolic, Exercise, Muscle, Genetic Counseling

Very long-chain acyl-CoA dehydrogenase (VLCAD) is a mitochondrial enzyme that breaks down long-chain fatty acids (14 to 20 carbons in length) for energy — a process called β-oxidation(https://pubmed.ncbi.nlm.nih.gov/9973285/). When VLCAD is impaired, long-chain fats accumulate, cells cannot generate ATP from fat,...

rs11568821 Intronic regulatory variant near the PDCD1 (PD-1) immune checkpoint locus that disrupts a RUNX1 transcription factor binding site, altering PD-1 expression and conferring susceptibility to systemic lupus erythematosus and multiple sclerosis

Chromosome 2 Risk Allele G Category Autoimmune Tolerance & T-Cell Regulation Tags Autoimmune, Lupus, Multiple Sclerosis, T-Cell Regulation, Immune & Autoimmune, Inflammation

PD-1 (Programmed Death-1, encoded by PDCD1) is one of the immune system's most powerful braking mechanisms. Expressed on activated T cells, PD-1 binds its ligands PD-L1 and PD-L2 on antigen-presenting cells and peripheral tissues, suppressing T-cell activation and preventing immune attacks on self-tissue. When this...

rs11591147 Loss-of-function variant that naturally lowers LDL cholesterol by 15-28% and reduces coronary disease risk by up to 47%

Chromosome 1 Risk Allele G Category Atherogenic Lipoproteins Tags Cardiovascular, Cholesterol, Diet, Statins

rs11591147 encodes the R46L (p.Arg46Leu) variant in PCSK9, a serine protease that regulates LDL cholesterol by promoting degradation of LDL receptors in the liver. This loss-of-function mutation is associated with 15-47% reductions in coronary heart disease risk , making it one of the most significant...

rs1165196 Missense variant in SLC17A1 (NPT1) encoding a Thr269Ile substitution; the G allele (Thr269) is a gain-of-function variant that enhances renal NPT1-mediated urate secretion and lowers gout risk, while the common A allele (Ile269) carries baseline NPT1 activity and higher gout susceptibility

Chromosome 6 Risk Allele A Category Uric Acid & Kidney Function Tags Gout, Uric Acid, Kidney Function, Renal Function, Micronutrients, Kidney

The kidneys are the primary route of uric acid excretion, and their efficiency depends on a balance between transporters that reabsorb urate from the filtrate and those that secrete it into urine for elimination. On the apical (urine-facing) surface of the proximal tubule, NPT1 (sodium-dependent phosphate transport...

rs116843064 Missense variant that reduces ANGPTL4's inhibition of lipoprotein lipase, lowering fasting triglycerides and decreasing coronary artery disease risk in carriers of the K40 allele

Chromosome 19 Risk Allele G Category Triglycerides & Fatty Acids Tags Triglycerides, Cardiovascular, Fat Metabolism, Cholesterol, Diet

Angiopoietin-like protein 4 (ANGPTL4()) acts as a brake on fat clearance. The E40K variant at rs116843064 partially disables this brake. Carriers of the K40 allele (the minor A allele) have less ANGPTL4-mediated LPL inhibition, leading to faster triglyceride clearance after meals and persistently lower fasting...

rs121434287 Pathogenic missense variant in the intestinal zinc transporter ZIP4, causing acrodermatitis enteropathica — a rare autosomal recessive disorder of severe zinc deficiency — when inherited in biallelic form

Chromosome 8 Risk Allele A Category Iron & Mineral Transport Tags Zinc, Minerals, Micronutrients, Digestive Health, Skin Health, Carrier Status

Every cell in your body needs zinc, yet humans have no meaningful way to store it. Every milligram must be absorbed fresh from the diet, almost entirely through the duodenum and proximal jejunum. The protein responsible for ferrying zinc from the gut lumen into intestinal cells is ZIP4(), a twelve-pass transmembrane...

rs121909547 Pathogenic missense variant in the antithrombin III heparin-binding domain; heterozygous carriers have antithrombin deficiency conferring an approximately 14-fold increased risk of venous thromboembolism

Chromosome 1 Risk Allele A Category Von Willebrand & Anticoagulant Proteins Tags Blood Clotting, Thrombophilia, Cardiovascular, Thrombosis, Blood Thinners

Antithrombin III — encoded by SERPINC1 — is the body's primary brake on the coagulation cascade. It neutralizes thrombin and activated Factor Xa, directly blocking the two central enzymes that form fibrin clot. When antithrombin works at full capacity, a runaway clotting reaction cannot occur. The Arg79Cys variant...