Research — GeneOps

rs4986790 Missense variant in Toll-like receptor 4 reducing bacterial endotoxin recognition and dampening inflammatory responses

Chromosome 9 Risk Allele G Category Innate Immunity & Infection Defense Tags Immune System, Inflammation, Autoimmune, Cardiovascular, Infectious Disease

Toll-like receptor 4 (TLR4)(https://www.ncbi.nlm.nih.gov/gene/7099) serves as the body's frontline defense against bacterial infections. The Asp299Gly variant (rs4986790), caused by an A-to-G transition at position 896 in the gene's coding sequence, replaces aspartic acid with glycine at amino acid position...

rs56062135 Intronic SMAD3 variant tagging the CAD-protective haplotype where the T allele reduces SMAD3 enhancer activity in arterial smooth muscle cells, lowering TGF-beta-driven vascular remodeling and coronary artery disease risk

Chromosome 15 Risk Allele C Category Coronary Artery Disease & Atherosclerosis Tags Cardiovascular, Atherosclerosis, Heart Disease, Inflammation, Fibrosis

Coronary artery disease begins not with blocked arteries but with dysfunctional artery walls — and a key player in that dysfunction is SMAD3, the principal intracellular messenger of TGF-beta (transforming growth factor-beta) signaling(https://pubmed.ncbi.nlm.nih.gov/30307970/). The rs56062135 variant sits within...

rs5749131 Upstream regulatory variant near TCN2 associated with reduced holotranscobalamin levels — the bioactive fraction of circulating vitamin B12 available for cellular uptake

Chromosome 22 Risk Allele A Category Vitamins & Nutrient Absorption Tags Vitamin B12, B Vitamins, Methylation, Homocysteine, Cardiovascular

Most vitamin B12 circulating in your blood is metabolically inert — bound to haptocorrin and unable to enter cells. Only 20–25% binds to transcobalamin II(), forming holotranscobalamin(https://pubmed.ncbi.nlm.nih.gov/21593512/) (holoTC). This active fraction is a far more sensitive marker of cellular B12 status than...

rs588765 Intronic eQTL in CHRNA5 that modulates alpha-5 nicotinic receptor mRNA expression levels, forming an independent risk signal for nicotine dependence and lung cancer distinct from the Asp398Asn coding variant (rs16969968)

Chromosome 15 Risk Allele T Category Mood & Behavior Tags Mental Health, Addiction, Smoking, Lung Cancer, Neurotransmitters

The CHRNA5 gene on chromosome 15q25.1 encodes the alpha-5 subunit of the neuronal nicotinic acetylcholine receptor — a critical component of the brain circuits that govern how aversive nicotine feels at high doses. Most research on this region has focused on rs16969968, an amino acid change (Asp398Asn) that blunts...

rs61754010 Pathogenic missense variant in the VWF propeptide D2 domain that introduces an aberrant N-glycosylation site, disrupting VWF multimerization and Weibel-Palade body storage; heterozygous carriers have type 2A von Willebrand disease with qualitative VWF deficiency and variable bleeding risk

Chromosome 12 Risk Allele C Category Von Willebrand & Anticoagulant Proteins Tags Blood Clotting, Cardiovascular, Carrier Status, Thrombosis, Genetic Counseling, Women's Health, Thrombophilia

Von Willebrand factor (VWF) is the first responder at a vascular injury — a multimeric protein that bridges damaged endothelium to platelets and chauffeurs factor VIII through the bloodstream. Its effectiveness depends critically on two things: being built into large multimers, and being stored in Weibel-Palade...

rs689466 Promoter variant in the PTGS2/COX-2 gene that reduces baseline COX-2 expression, increasing susceptibility to ulcerative colitis and modifying colorectal cancer and cardiovascular risk

Chromosome 1 Risk Allele C Category IBD & Mucosal Immunity Tags Autoimmune, Inflammation, IBD, Ulcerative Colitis, Colorectal Cancer, Smoking Interaction, Endocannabinoid, Pain Sensitivity, Pain Management

COX-2(https://www.ncbi.nlm.nih.gov/gene/5743) is the enzyme that makes prostaglandins — the molecular messengers that drive fever, pain, and the redness and swelling of inflammation. It is also the primary target of NSAIDs including aspirin, ibuprofen, and the now-restricted COX-2 selective inhibitors (coxibs). The...

rs6947337 Activin A signaling variant near INHBA linking adipocyte dysfunction to shared migraine and type 2 diabetes risk

Chromosome 7 Risk Allele A Category Appetite & Obesity Tags Obesity, Fat Metabolism, Inflammation, Diabetes, Adipogenesis, Metabolic Health

INHBA encodes the beta-A subunit of activin A(), a TGF-beta superfamily member that plays a central role in adipocyte biology. The rs6947337 variant lies in an intergenic region approximately 110 kb downstream of INHBA on chromosome 7p14.1 and was identified as a novel shared risk locus between migraine and type 2...

rs72552272 Pathogenic missense in the y+LAT1 cationic amino acid transporter causing lysinuric protein intolerance, a recessive disorder of dibasic amino acid transport with hyperammonemia, protein aversion, and multi-organ complications.

Chromosome 14 Risk Allele C Category Metabolic Enzymes & Rare Disorders Tags Urea Cycle, Metabolic, Kidney, Lung Health, Bone Health, Carrier Status

Every meal you eat is a negotiation between the gut wall and your bloodstream. y+LAT1(https://pubmed.ncbi.nlm.nih.gov/10655553/) sits at the basolateral membrane of intestinal and renal tubular cells, its job being to ferry the three dibasic amino acids — lysine, arginine, and ornithine — out of epithelial cells and...

rs7521902 Intronic variant near WNT4 on chromosome 1p36.12 associated in multiple GWAS with elevated risk of endometriosis, particularly moderate-to-severe (stage III/IV) disease, and with uterine fibroid susceptibility through disrupted Wnt signaling in the endometrium.

Chromosome 1 Risk Allele A Category Endometriosis & Uterine Health Tags Endometriosis, Uterine Fibroids, Fertility, Reproductive Health, Hormones

WNT4 encodes one of the Wnt family of secreted signaling proteins, a group essential for embryonic development of the female reproductive tract and for the monthly remodeling of the uterine lining. The protein coordinates the formation of Müllerian duct structures — the precursors to the uterus, fallopian tubes, and...

rs7753394 Intergenic tag SNP in the 6q23 regulatory region upstream of TNFAIP3 that co-tags haplotypes associated with altered A20 expression and susceptibility to multiple autoimmune and inflammatory conditions

Chromosome 6 Risk Allele C Category TNF, NF-kB & Inflammatory Cytokines Tags Autoimmune, Inflammation, Rheumatoid Arthritis, IBD, Innate Immunity, T-Cell Regulation

A key principle in genomics is that most disease-associated variants found by genome-wide association studies are not located in protein-coding sequences — they sit in the regulatory landscape between genes, tuning how much of a critical protein gets made. rs7753394 exemplifies this principle. It resides on...