Research — GeneOps

rs1799999 Missense variant in the skeletal muscle glycogen-targeting subunit of protein phosphatase 1 (PP1); reduces effective PP1 activity at the glycogen particle, impairing insulin-stimulated glycogen synthesis and increasing type 2 diabetes risk

Chromosome 7 Risk Allele A Category Blood Sugar & Diabetes Tags Insulin Resistance, Diabetes, Metabolic, Muscle, Energy Metabolism, Fat Metabolism

Skeletal muscle is the largest glucose sink in the human body, and most of that glucose enters storage as glycogen(). The enzyme that builds glycogen — glycogen synthase — is held in check by phosphorylation and activated when protein phosphatase 1 (PP1)() removes those inhibitory phosphate groups. PP1 doesn't float...

rs1800566 Phase II detoxification enzyme that reduces quinones and recycles CoQ10 to its active ubiquinol form; variant causes near-complete loss of enzyme activity

Chromosome 16 Risk Allele A Category Methylation & Detox Tags Detoxification, Phase II, Oxidative Stress, Antioxidants, Cardiovascular, NRF2 Target

NQO1 (NAD(P)H:quinone oxidoreductase 1) is a Phase II detoxification enzyme() that performs an unusual and critically important reaction: it reduces toxic quinones directly to stable hydroquinones via a two-electron transfer, completely bypassing the dangerous one-electron semiquinone radical() intermediate. This...

rs2069526 Intronic CYP1A2 variant near the 5' end; G allele is associated with altered metabolic ratios for CYP1A2 substrates including escitalopram

Chromosome 15 Risk Allele G Category Pharmacogenomics Tags Drug Metabolism, Pharmacogenomics, Caffeine, Antidepressants, Smoking Interaction

CYP1A2 is the liver enzyme responsible for breaking down roughly 95% of caffeine, as well as several important medications including clozapine, theophylline, and escitalopram. The enzyme's activity varies substantially between individuals — up to 40-fold — driven by a combination of genetic polymorphisms, smoking...

rs2234693 Estrogen receptor alpha intron variant affecting receptor expression and estrogen sensitivity

Chromosome 6 Risk Allele T Category Hormones & Sleep Tags Hormones & Thyroid, Bone Health, Cardiovascular, Estrogen, Menopause

The ESR1 gene encodes estrogen receptor alpha (ERα), one of two primary mediators through which estrogen exerts its effects on bone, cardiovascular, and reproductive tissues. This intron 1 variant (also called PvuII or -397TC) lies 397 base pairs upstream of exon 2(https://pubmed.ncbi.nlm.nih.gov/32682401/) and has...

rs2279525 3' UTR variant in the PGC-1alpha gene that may alter PPARGC1A mRNA stability or miRNA regulation, with potential downstream effects on mitochondrial biogenesis and fat oxidation capacity

Chromosome 4 Risk Allele C Category Fat Storage & Energy Tags Mitochondria, Energy Metabolism, Fat Metabolism, Insulin Resistance, Adipogenesis, Diabetes

PPARGC1A encodes PGC-1alpha(). If PPARG is the nuclear receptor that controls adipocyte differentiation, PGC-1alpha is the coactivator that powers the engine running those processes. Every time your cells build new mitochondria — after endurance training, during cold exposure, in response to caloric restriction —...

rs2524299 Intronic regulatory variant in FADS2 (Block 2 haplotype) that reduces basal FADS1 and FADS2 expression through a conserved intron 1 regulatory locus, impairing delta-6 desaturase activity and lowering circulating arachidonic acid, EPA, and DHA; captures an independent regulatory signal from the rs174568/rs174575 haplotype block

Chromosome 11 Risk Allele T Category Triglycerides & Fatty Acids Tags Omega-3, Fat Metabolism, Triglycerides, Cardiovascular, Diet, Inflammation

The FADS gene cluster on chromosome 11 contains dozens of variants that affect how efficiently your body converts short-chain dietary fats into long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic acid, EPA, and DHA. Most of these variants travel together in a single large block of linkage...

rs2764264 Intronic FOXO3 variant that disrupts an NKX3 transcription factor binding site; the longevity-associated C allele confers protection in male centenarians independent of rs2802292

Chromosome 6 Risk Allele T Category Longevity & Aging Tags Longevity, Aging, Cardiovascular, Diabetes, Oxidative Stress, Inflammation, Ovarian Reserve, Menopause

FOXO3 is one of only two genes replicated for longevity associations across every human population tested—the other is APOE. Within FOXO3's vast 101,625 base-pair second intron, several variants independently contribute to exceptional lifespan. rs2764264 is the third major longevity signal in this region, alongside...

rs28937900 The most common pathogenic mutation in FKRP causing limb-girdle muscular dystrophy R9 (LGMD R9) in European populations; homozygous carriers develop progressive proximal muscle weakness

Chromosome 19 Risk Allele A Category Fitness & Body Tags Muscle, Fitness, Cardiovascular, Carrier Status, Congenital, Genetic Counseling

The FKRP gene encodes fukutin-related protein(), a glycosyltransferase enzyme that modifies the surface of muscle fiber membranes. The c.826CA mutation (L276I) substitutes leucine with isoleucine at amino acid position 276, partially disrupting this enzyme's function. In the autosomal recessive inheritance pattern,...

rs3093059 Promoter variant that elevates baseline C-reactive protein levels, increasing cardiovascular inflammation risk and stroke susceptibility

Chromosome 1 Risk Allele G Category Vascular Inflammation & Remodeling Tags Inflammation, Cardiovascular, Atherosclerosis, Hypertension, Biomarkers

C-reactive protein (CRP) is the liver's first responder to inflammatory signals. Under normal conditions it circulates at low concentrations, but during acute infection or tissue injury it can surge more than 1,000-fold within hours. What's less appreciated is that baseline CRP — the level you carry when healthy —...

rs387906249 Pathogenic ACADVL frameshift deletion causing premature protein truncation; heterozygous carriers are healthy but carry reproductive risk, while biallelic disruption causes VLCAD deficiency requiring lifelong dietary management

Chromosome 17 Risk Allele D Category Metabolic Enzymes & Rare Disorders Tags Fat Metabolism, Mitochondria, Carrier Status, Energy Metabolism, Genetic Counseling, Congenital

Every cell in the body can burn fat for fuel, but only if the right enzymes are present to start the process. Very long-chain acyl-CoA dehydrogenase (VLCAD)(https://www.ncbi.nlm.nih.gov/books/NBK6816/) is the gatekeeper for very long-chain fats — the dominant form of stored body fat and a critical fuel during...