Research — GeneOps

rs622342 Intronic variant in the OCT1 organic cation transporter reducing hepatic metformin uptake and altering response to multiple cation-transported drugs

Chromosome 6 Risk Allele C Category Pharmacogenomics Tags Drug Metabolism, Pharmacogenomics, Diabetes, Metformin

SLC22A1 encodes organic cation transporter 1 (OCT1), the primary transporter responsible for shuttling metformin from the bloodstream into hepatocytes — the liver cells where metformin exerts its glucose-lowering effect. Without efficient OCT1 transport, metformin cannot reach its intracellular target AMP-activated...

rs63749911 Rare pathogenic PSEN1 missense variant substituting leucine for phenylalanine at position 177 in the gamma-secretase catalytic subunit; elevates Aβ42/Aβ40 ratio with relatively preserved total cleavage activity, classified as pathogenic for early-onset familial Alzheimer's disease

Chromosome 14 Risk Allele C Category Neurology & Cognition Tags Alzheimer's, Neurodegeneration, Dementia, Genetic Counseling, Cognitive Decline, Amyloidosis

Presenilin-1(https://www.ncbi.nlm.nih.gov/gene/5663) is the primary molecular switch governing how the brain processes amyloid precursor protein (APP). When presenilin-1 works correctly, gamma-secretase trims APP into shorter, soluble peptides that are cleared without harm. When a PSEN1 mutation shifts that trimming...

rs914458 Downstream regulatory variant 10 kb 3' of PTPN1 (PTP1B) associated with type 2 diabetes risk (OR 1.43) and moderate obesity in a French population study; tags the regulatory region flanking the PTP1B negative-regulator locus

Chromosome 20 Risk Allele C Category Blood Sugar & Diabetes Tags Insulin, Insulin Resistance, Diabetes, Obesity, Energy Metabolism, Metabolic Syndrome

Protein tyrosine phosphatase 1B() (PTP1B) is one of the most intensively studied drug targets in metabolic medicine. It acts as a molecular brake on two critical hormonal pathways: insulin signaling (which controls blood glucose) and leptin signaling (which controls appetite and body weight). When PTP1B is...

rs61816766 Intronic FLG-locus variant strongly associated with atopic dermatitis — the C allele marks filaggrin deficiency through a skin-specific mechanism with a larger effect size (OR 1.66) than the classical R501X null allele

Chromosome 1 Risk Allele C Category Allergy & Atopic Disease Tags Skin Health, Inflammation, Immune & Gut, Food Sensitivity, Asthma, Immune System

Filaggrin is the structural protein that builds the waterproof outer layer of your skin, retains moisture, and keeps allergens out. The FLG gene encodes profilaggrin(https://pubmed.ncbi.nlm.nih.gov/16550169/). Most studied FLG variants are loss-of-function null alleles that introduce premature stop codons (R501X,...

rs63750066 Rare pathogenic missense variant in APP at the gamma-secretase cleavage site causing familial early-onset Alzheimer's disease with cerebral amyloid angiopathy; the "Calabrian" founder mutation originating in southern Italy over 1,000 years ago

Chromosome 21 Risk Allele T Category Neurology & Cognition Tags Alzheimer's, Neurological Risk, Neurodegeneration, Amyloidosis, Genetic Counseling, Cardiovascular

The amyloid precursor protein (APP) is processed by a series of secretase enzymes that determine whether it generates toxic amyloid-beta fragments or harmless non-amyloidogenic peptides. The A713T variant (rs63750066) introduces an alanine-to-threonine substitution at position 713 of APP — a residue lying directly...

rs640561 Intergenic variant near LRRIQ3 associated with problematic opioid prescription use in a large GWAS; the T allele tags elevated risk of using opioids not as prescribed

Chromosome 1 Risk Allele T Category Pharmacogenomics Tags Pharmacogenomics, Substance Use, Pain Medication, Chronic Pain, Addiction

Most genetic research on opioid response focuses on the mu-opioid receptor gene OPRM1 or enzymes that metabolize specific drugs. But a 2021 genome-wide association study of problematic opioid prescription use pointed to an unexpected locus on chromosome 1 — a variant near...

rs9402571 Regulatory variant in SGK1 (serum/glucocorticoid regulated kinase 1) — the minor G allele is associated with improved insulin secretion in lean individuals and a modest reduction in type 2 diabetes prevalence, while also modifying blood pressure response to high dietary salt intake.

Chromosome 6 Risk Allele T Category Blood Sugar & Diabetes Tags Insulin, Fasting Glucose, Diabetes, Insulin Resistance, Blood Pressure, Stress Response

SGK1 (serum/glucocorticoid regulated kinase 1) sits at a metabolic crossroads: it is switched on by two of the body's most powerful stress hormones — glucocorticoids such as cortisol and mineralocorticoids such as aldosterone — and it translates those signals into changes in ion channel activity, glucose transport,...

rs63751122 Rare pathogenic missense variant in APP near the gamma-secretase cleavage site causing autosomal dominant early-onset familial Alzheimer's disease; the "Australian" mutation first identified in an early-onset kindred, increasing amyloid-beta42/43 production 1.4- to 1.9-fold

Chromosome 21 Risk Allele G Category Neurology & Cognition Tags Alzheimer's, Neurological Risk, Neurodegeneration, Amyloidosis, Genetic Counseling, Dementia

The amyloid precursor protein (APP) is expressed throughout the brain, where it is processed by a cascade of secretase enzymes. When cleavage goes wrong — as it does in familial Alzheimer's disease — the result is excess production of amyloid-beta 42/43(https://pubmed.ncbi.nlm.nih.gov/41709913/), which forms the...

rs6413419 Missense variant (Val179Ile) defining the CYP2E1*4 allele; associated with altered CYP2E1 enzyme activity affecting metabolism of acetaminophen, ethanol, isoniazid, halogenated anesthetics, benzene, and tobacco nitrosamines

Chromosome 10 Risk Allele A Category Pharmacogenomics Tags Drug Metabolism, Pharmacogenomics, Liver Health, Alcohol, Carcinogen Metabolism, Anesthesia

CYP2E1 (cytochrome P450 2E1) is the liver's front-line enzyme for metabolising a surprisingly diverse set of molecules — from the pain reliever in your medicine cabinet to the alcohol in a glass of wine, the anaesthetic gases used in surgery, and the industrial chemicals benzene and carbon tetrachloride. CYP2E1 is...

rs6589702 Intergenic regulatory variant near the PRG2/PRG3 eosinophil granule protein cluster at chromosome 11; A allele may influence PRG2 expression and eosinophil major basic protein levels, implicated in eosinophil-mediated allergic inflammation and atopic disease susceptibility

Chromosome 11 Risk Allele A Category Allergy & Atopic Disease Tags Asthma, Inflammation, Immune System, IBD, Immune & Autoimmune

Inside every eosinophil sits a crystalline granule containing one of the immune system's most potent cytotoxic proteins: major basic protein (MBP)(https://pubmed.ncbi.nlm.nih.gov/11170744/). Under normal conditions, eosinophils patrol mucosal surfaces and deploy MBP against parasites — an ancient and effective...