Research — GeneOps

rs12487736 Missense variant in the SCAP cholesterol-sensor gene (Val798Ile); the C allele (coding-strand G) impairs the SCAP–SREBP-2 feedback axis, promoting cholesterol accumulation in vascular cells and elevating sudden cardiac death risk in combination with the SREBF2 Gly595Ala variant

Chromosome 3 Risk Allele C Category Atherogenic Lipoproteins Tags Cholesterol, Cardiovascular, Atherosclerosis, Heart Disease, Lipid Metabolism, Statins

Before a cell can respond to low cholesterol by making more, it needs to sense the deficit. That sensing job belongs to SCAP (SREBP cleavage-activating protein)(https://pubmed.ncbi.nlm.nih.gov/19116028/). When cholesterol is plentiful, SCAP is detained at the ER by INSIG proteins. When cholesterol drops, SCAP...

rs1537415 Intronic variant in GLT6D1 reducing GATA-3 transcription factor binding in T cells, increasing aggressive periodontitis risk

Chromosome 9 Risk Allele C Category Dental & Oral Health Tags Dental & Oral Health, Inflammation, Immune System, Immune Response, Bone Health

GLT6D1 (glycosyltransferase 6 domain containing 1)(https://omim.org/entry/613699) was the first gene ever identified through a genome-wide association study to influence susceptibility to aggressive periodontitis. The rs1537415 variant sits within intron 2 of this gene and was discovered in a landmark 2010 study of...

rs17879961 Missense variant in the CHEK2 FHA domain that impairs phosphoprotein binding and dimerization, conferring moderate-penetrance susceptibility to breast, colorectal, thyroid, prostate, and kidney cancer

Chromosome 22 Risk Allele G Category Cancer Risk Tags Cancer Risk, DNA Repair, Double-Strand Break Repair, Cancer Screening, Breast Cancer, Colorectal Cancer

Every time one of your cells divides, its entire genome must be copied with near-perfect fidelity. When copying errors create double-strand DNA breaks, a surveillance network activates to halt the cell cycle until repairs are complete. CHEK2 (checkpoint kinase 2) is a critical node in this network — it receives the...

rs10166942 Upstream regulatory variant of the cold-sensing TRPM8 channel that modulates migraine susceptibility, cold pain sensitivity, and brown adipose thermogenesis

Chromosome 2 Risk Allele T Category Neurology & Cognition Tags Brain Health, Pain Sensitivity, Thermogenesis, Metabolic, Migraine

Transient receptor potential melastatin 8() (TRPM8) is the body's primary cold-sensing ion channel, expressed in sensory neurons of the dorsal root ganglia() and trigeminal ganglia. The variant rs10166942 sits 950 base pairs upstream of the TRPM8 transcription start site and directly influences how much of this...

rs1042044 GLP-1 receptor variant in intracellular loop 2 that alters receptor surface expression and signaling, influencing antipsychotic response, cortisol regulation, and bone metabolism

Chromosome 6 Risk Allele A Category Pharmacogenomics Tags Drug Response, Pharmacogenomics, Obesity, Diabetes

The GLP-1 receptor (GLP1R) mediates the actions of glucagon-like peptide 1(), one of the body's most important metabolic hormones. GLP1R is also the target of blockbuster medications like semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro). The rs1042044 variant causes a leucine-to-phenylalanine substitution at...

rs10423928 Intronic GIPR variant that reduces functional GIP receptor expression via altered splicing, impairing the incretin-mediated insulin response while paradoxically lowering BMI

Chromosome 19 Risk Allele A Category Blood Sugar & Diabetes Tags Diabetes, Insulin, Diet, Cardiovascular, Fat Metabolism

Every time you eat, your gut releases a hormone called GIP (glucose-dependent insulinotropic polypeptide)(https://pubmed.ncbi.nlm.nih.gov/20081860/) that signals your pancreas to release insulin. The GIPR gene encodes the receptor that detects this signal. rs10423928 is a common variant in an intron of GIPR that...

rs10483099 Intronic variant near QDPR that affects BH4 recycling efficiency, influencing neurotransmitter synthesis and nitric oxide production

Chromosome 22 Risk Allele T Category Methylation & Detox Tags Methylation & Detox, Neurotransmitters, Nitric Oxide, B Vitamins, Cardiovascular, Dopamine

Your body cannot continuously synthesize tetrahydrobiopterin (BH4)(https://pubmed.ncbi.nlm.nih.gov/33903016/) from scratch fast enough to meet demand. Instead, it relies on QDPR — quinoid dihydropteridine reductase — to continuously regenerate BH4 from its spent, oxidized form. Every time a dopamine, serotonin, or...

rs104894137 Missense variant in CYP17A1 reducing both 17α-hydroxylase and 17,20-lyase activities to 40–45% of normal; causes partial combined 17α-hydroxylase/17,20-lyase deficiency with variable sex steroid deficiency, mineralocorticoid excess, and impaired fertility

Chromosome 10 Risk Allele T Category Reproductive Hormones Tags Fertility, Reproductive Health, Steroid Hormones, Steroid Metabolism, Hormones, Hypertension

CYP17A1(https://www.ncbi.nlm.nih.gov/gene/1586) sits at the branch point between the mineralocorticoid and sex steroid pathways. When CYP17A1 works normally, the adrenal glands and gonads can produce cortisol and sex hormones. When it is impaired, the steroid synthesis pipeline is diverted: mineralocorticoid...

rs104894503 Pathogenic alpha-tropomyosin missense variant that increases thin filament calcium sensitivity, causing familial hypertrophic cardiomyopathy; a founder mutation accounting for ~6.5% of HCM cases in Finland

Chromosome 15 Risk Allele A Category Cardiomyopathy & Structural Heart Tags Heart Disease, Cardiovascular, Genetic Counseling, Carrier Status, Biomarkers

The heart's ability to pump depends on a precisely timed molecular switch inside every muscle fiber. Tropomyosin(https://pubmed.ncbi.nlm.nih.gov/21376702/) sits at the center of this switch. In the resting heart, tropomyosin physically blocks myosin from grabbing actin. When calcium floods in during a heartbeat,...

rs104895467 Rare NOD2 missense variant (Asn852Ser) that impairs innate immune sensing of bacterial peptidoglycan and is associated with Crohn's disease risk; markedly enriched in Ashkenazi Jewish populations (~1.6%)

Chromosome 16 Risk Allele G Category IBD & Mucosal Immunity Tags Innate Immunity, Inflammatory Bowel Disease, Crohn's Disease, Gut Microbiome, Bacterial Sensing, Ancestry-Specific

Deep inside your intestinal lining, immune sentinel cells continuously survey the bacterial population that colonizes your gut. NOD2 (nucleotide-binding oligomerization domain-containing protein 2)(https://pubmed.ncbi.nlm.nih.gov/11385576/) is the sentinel's core machinery. NOD2 was identified in 2001 as the first...