Research — GeneOps

rs55886062 No-function DPYD star allele (I560S) causing severe DPD deficiency; one of four CPIC high-priority variants requiring 50% fluoropyrimidine dose reduction

Chromosome 1 Risk Allele C Category Pharmacogenomics Tags Drug Metabolism, Pharmacogenomics, Chemotherapy, Cancer Treatment, Fluoropyrimidine Toxicity, Pyrimidine Catabolism

DPYD encodes dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme(https://pubmed.ncbi.nlm.nih.gov/29152729/) that metabolises fluoropyrimidine chemotherapy drugs. DPYD13 (c.1679TG, p.Ile560Ser) is a rare missense variant that produces an essentially non-functional enzyme — first described in patients...

rs61759167 Intronic PRDM16 variant reaching genome-wide significance in the first motion sickness GWAS, with the same risk allele independently associated with antimigraine medication use — pointing to a shared genetic basis for vestibular vulnerability and migraine susceptibility

Chromosome 1 Risk Allele T Category Neurology & Cognition Tags Migraine, Brain Health, Neurological Risk, Pain Sensitivity, Sensorineural

Most people think of motion sickness as a minor inconvenience. Genetics says otherwise. In 2015, the first genome-wide association study of motion sickness — analyzing 80,494 participants(https://pubmed.ncbi.nlm.nih.gov/25628336/) — found 35 SNPs reaching genome-wide significance, implicating genes involved in inner...

rs689 Tag SNP for the insulin gene VNTR promoter — shorter Class I repeats raise T1D risk by reducing thymic insulin expression

Chromosome 11 Risk Allele A Category Blood Sugar & Diabetes Tags Type 1 Diabetes, Autoimmune, Insulin, T-Cell Regulation, RNA Splicing, Diabetes

The insulin gene (INS) on chromosome 11p15.5 controls more than blood sugar regulation. A polymorphic repeat region in its promoter — the Variable Number Tandem Repeat(https://pubmed.ncbi.nlm.nih.gov/9242475/) (VNTR) — determines how much insulin is expressed in the thymus, the organ that trains the immune system to...

rs819147 Regulatory variant affecting S-adenosylhomocysteine hydrolase expression, influencing methylation cycle balance and SAH clearance

Chromosome 20 Risk Allele C Category Methylation & Detox Tags Methylation, Homocysteine, Cardiovascular, Inflammation, B Vitamins, Detoxification

The AHCY gene produces S-adenosylhomocysteine hydrolase, the only mammalian enzyme capable of converting S-adenosylhomocysteine (SAH) to homocysteine and adenosine. This seemingly simple reaction is critical: SAH is a potent inhibitor of methyltransferases(https://pubmed.ncbi.nlm.nih.gov/33869213/). When AHCY...

rs9565309 Regulatory variant near FBXL3 that modulates circadian period length; the C allele is associated with an OR=1.19 for morningness chronotype in a 697,828-person GWAS

Chromosome 13 Risk Allele T Category Hormones & Sleep Tags Sleep, Circadian, Chronotype, Hormones, Fatigue

Inside every cell, the circadian clock ticks through a 24-hour negative feedback loop: the CLOCK:BMAL1 protein complex drives expression of PER and CRY genes; PER and CRY proteins then feed back to inhibit CLOCK:BMAL1, completing one cycle. The speed of this loop — and therefore whether your internal day runs fast...

rs3806933 Functional promoter variant in TSLP that creates an AP-1 transcription factor binding site; the T risk allele increases long-form TSLP expression in airway epithelial cells, raising susceptibility to asthma, allergic rhinitis, and atopic conditions (OR 1.29–1.32)

Chromosome 5 Risk Allele T Category Allergy & Atopic Disease Tags Asthma, Inflammation, Autoimmune, Immune System, Skin Health, Lung Health

Your immune system's response to allergens, viruses, and skin-barrier disruptions begins with a deceptively simple signal: the release of thymic stromal lymphopoietin (TSLP)(https://www.ncbi.nlm.nih.gov/gene/85480) from epithelial cells. TSLP is the "break-glass" alarm that tells the immune system an environmental...

rs55897648 CYP2E1*3 missense variant with no demonstrated change in enzyme activity for acetaminophen, ethanol, or industrial solvent substrates

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

CYP2E1 (cytochrome P450 2E1) is the liver enzyme responsible for metabolizing a diverse and clinically important set of substrates: acetaminophen(https://pubmed.ncbi.nlm.nih.gov/17020953/), ethanol at high concentrations, front-line anti-tuberculosis drugs including isoniazid, volatile anesthetics such as halothane...

rs61761208 Missense mutation replacing asparagine with tyrosine at position 141 of presenilin-2, causing early-onset autosomal dominant Alzheimer's disease in a Chinese Han family; absent from gnomAD and classified pathogenic by ACMG criteria

Chromosome 1 Risk Allele T Category Neurology & Cognition Tags Alzheimer's, Neurodegeneration, Dementia, Brain Health, Genetic Counseling, Cognitive Decline

The PSEN2 gene encodes presenilin-2, one of four subunits of the γ-secretase complex(https://www.alzforum.org/alzpedia/presenilin-2-psen2), the enzyme responsible for cleaving amyloid precursor protein (APP) within its transmembrane domain. Presenilin-2 forms the catalytic core of this complex, contributing the two...

rs7202877 Intergenic variant near CTRB1/CTRB2 that regulates chymotrypsinogen expression and GLP-1-stimulated insulin secretion; T allele carriers have mildly impaired incretin-driven beta-cell response and modestly elevated type 2 diabetes risk

Chromosome 16 Risk Allele T Category Blood Sugar & Diabetes Tags Diabetes, Pancreatic Beta Cell, Insulin, Energy Metabolism, Pharmacogenomics, Metabolic Health

Every time you eat, your small intestine releases hormones called incretins — principally GLP-1(https://pubmed.ncbi.nlm.nih.gov/23674605/) — that tell your pancreatic beta cells to release insulin in proportion to the meal's size. This variant near the CTRB1 and CTRB2 genes determines how efficiently that signal...

rs828903 Intronic variant in the mitochondrial folate enzyme MTHFD2, influencing one-carbon metabolism and linked to folate receptor autoantibody levels and embryonic development risk

Chromosome 2 Risk Allele G Category Methylation & Detox Tags Methylation, Folate, B Vitamins, Embryo Development, Cancer Risk, Mitochondria

MTHFD2 (methylenetetrahydrofolate dehydrogenase 2) is the mitochondrial isoform of the folate-processing enzyme family. While MTHFD1 handles the same reactions in the cytoplasm, MTHFD2 operates in the mitochondrial matrix(), converting 5,10-methyleneTHF to 10-formylTHF and feeding one-carbon units into the purine...