Research — GeneOps

rs387907200 Missense/splicing variant in sepiapterin reductase that reduces BH4 biosynthesis to ~15% of normal, impairing dopamine and serotonin production; causes dopa-responsive dystonia in biallelic carriers

Chromosome 2 Risk Allele T Category Methylation & Detox Tags Methylation & Detox, Neurotransmitters, Dopamine, Serotonin, Detoxification, Parkinson's

Deep in the brainstem and striatum, three enzymes are quietly producing dopamine, serotonin, and norepinephrine — the neurotransmitters that govern movement, mood, and alertness. All three depend on a single small molecule: tetrahydrobiopterin (BH4)(https://pubmed.ncbi.nlm.nih.gov/11443547/). The SPR gene encodes...

rs3918290 Most critical pharmacogenomic variant causing complete loss of DPD enzyme function; increases fatal 5-FU/capecitabine toxicity risk 25-fold without dose reduction

Chromosome 1 Risk Allele T 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/) responsible for breaking down fluoropyrimidine chemotherapy drugs. The DPYD2A variant (also known as IVS14+1GA) is a | G-to-A transition at the invariant splice donor site of intron 14, causing...

rs5219 Controls the pancreatic beta-cell potassium channel that regulates insulin secretion and determines sulfonylurea drug response

Chromosome 11 Risk Allele T Category Blood Sugar & Diabetes Tags Diabetes, Insulin, Metabolic, Drug Metabolism, Cardiovascular, Pharmacogenomics

Your pancreatic beta cells use a remarkable molecular gate called the KATP channel to sense blood sugar and release insulin. KCNJ11 encodes Kir6.2, the pore-forming subunit of this channel. When blood glucose rises, ATP builds up inside the beta cell, closes the KATP...

rs5751876 Adenosine A2A receptor variant that determines individual sensitivity to caffeine's effects on anxiety and sleep

Chromosome 22 Risk Allele T Category Hormones & Sleep Tags Sleep, Caffeine, Anxiety, Neurotransmitters, Arousal

Every cup of coffee triggers a molecular contest inside your brain. Caffeine works by blocking adenosine() from binding to its receptors, particularly the A2A receptor() encoded by the ADORA2A gene. The rs5751876 variant determines how strongly your brain responds to this caffeine blockade — making some people...

rs964184 Common regulatory variant at the APOA5-ZNF259 locus; G allele reduces ApoAV protein levels, impairing triglyceride clearance and raising plasma TG by ~13% per allele — one of the strongest common GWAS signals for triglycerides

Chromosome 11 Risk Allele G Category Triglycerides & Fatty Acids Tags Triglycerides, Cardiovascular, Fat Metabolism, Diet, Cholesterol

At chromosome 11q23.3 sits a tightly packed cluster of lipid-metabolism genes — APOA5, APOA4, APOC3, and APOA1 — flanked by ZNF259 (also known as ZPR1) and BUD13. The rs964184 variant lies in the 3' untranslated region of ZNF259, but its most important effect is on the neighboring APOA5 gene, which encodes...

rs9817428 Intronic PPARG tagSNP with cross-ethnic replication for type 2 diabetes risk — located in the master regulator of adipogenesis and insulin sensitivity

Chromosome 3 Risk Allele A Category Fat Storage & Energy Tags Adipogenesis, Diabetes, Insulin Resistance, Metabolic, Fat Metabolism, Diet

PPARG (Peroxisome Proliferator-Activated Receptor Gamma()) is one of the most clinically and pharmacologically significant metabolic genes in the human genome. rs9817428 is an intronic variant within PPARG that has accumulated cross-ethnic replication evidence for modest but consistent effects on type 2 diabetes...

rs2602899 Regulatory SNP in the ADH5 promoter at a potential NF-kB binding site; the protective T allele reduces GSNOR expression, preserving the bronchodilator S-nitrosoglutathione and lowering childhood asthma risk

Chromosome 4 Risk Allele C Category Allergy & Atopic Disease Tags Asthma, Nitric Oxide, Inflammation, Detoxification, Respiratory Infections, Xenobiotics

Your airways produce a natural bronchodilator called S-nitrosoglutathione (GSNO)(https://pubmed.ncbi.nlm.nih.gov/15919956/). The enzyme that breaks GSNO down is GSNOR( https://pubmed.ncbi.nlm.nih.gov/28393572/). The rs2602899 variant sits in the ADH5 gene's promoter at a potential binding site for NF-kB(...

rs3756059 Intronic SNCA variant at the 5′ locus associated with REM sleep behavior disorder risk — the strongest genetic prodromal marker for Lewy body neurodegeneration

Chromosome 4 Risk Allele A Category Neurology & Cognition Tags Neurological Risk, Parkinson's, Neurodegeneration, Sleep, Brain Health

REM sleep behavior disorder (RBD)(https://pubmed.ncbi.nlm.nih.gov/36470867/) is not merely a sleep nuisance. It is the strongest known prodromal marker of synucleinopathy: roughly 80% of people with isolated (idiopathic) RBD eventually develop Parkinson's disease, dementia with Lewy bodies (DLB), or multiple system...

rs4148323 Phase II glucuronidation enzyme that metabolizes bilirubin and many drugs including irinotecan; reduced activity causes Gilbert syndrome and severe chemotherapy toxicity

Chromosome 2 Risk Allele A Category Pharmacogenomics Tags Pharmacogenomics, Drug Metabolism, Chemotherapy, Cancer Treatment, Liver Health, Bilirubin, Statins, Cardiovascular, Phase II, Detoxification

UGT1A1 (UDP-glucuronosyltransferase 1A1) is a Phase II detoxification enzyme responsible for glucuronidation(https://pubmed.ncbi.nlm.nih.gov/24492252/). Its primary job is metabolizing bilirubin, the yellow breakdown product of red blood cells, but it also processes many pharmaceutical drugs including the...

rs4659744 Intronic MTR variant that tags the folate/B12-dependent remethylation locus and associates with altered one-carbon metabolic balance

Chromosome 1 Risk Allele G Category Methylation & Detox Tags Methylation, B Vitamins, Homocysteine, Folate

Methionine synthase (MTR) performs one of the most critical reactions in one-carbon metabolism: it uses methylcobalamin (active vitamin B12) as a cofactor to transfer a methyl group from 5-methyltetrahydrofolate (methylfolate) onto homocysteine, converting it to methionine. This single reaction simultaneously clears...