Research — GeneOps

rs2234067 Upstream regulatory variant near ETV7, an interferon-inducible transcriptional repressor; the common C allele is associated with moderately increased rheumatoid arthritis risk, while the rare A allele is protective

Chromosome 6 Risk Allele C Category Interferon Signaling & Systemic Autoimmune Tags Rheumatoid Arthritis, Autoimmune, Inflammation, Interferon, T-Cell Regulation, Immune Response

Every immune response needs an accelerator and a brake. ETV7 is one of the immune system's most important molecular brakes — an interferon-stimulated gene (https://pubmed.ncbi.nlm.nih.gov/34257104/) that feeds back to suppress the very immune cascade that activated it. The common variant tagged by rs2234067 lies...

rs2268797 Intronic variant in SRD5A2 tagging haplotype backgrounds that differ in 5-alpha-reductase type 2 activity; associated with sperm motility differences in normozoospermic men

Chromosome 2 Risk Allele C Category Reproductive Hormones Tags Male Fertility, Sperm Quality, Testosterone, Steroid Metabolism, Reproductive Health, Fertility

Every man's reproductive biology depends on a precise balance between testosterone and dihydrotestosterone (DHT)(https://www.ncbi.nlm.nih.gov/gene/6716). The enzyme that makes DHT — steroid 5-alpha-reductase type 2, encoded by SRD5A2 — is most active in the prostate, genital skin, and seminal vesicles. Variants...

rs2301612 Common ADAMTS13 missense variant substituting glutamate for glutamine at position 448; the G allele acts as a context-dependent modifier of ADAMTS13 enzyme function and is associated with higher rates of atrial fibrillation and cerebral ischemic events in coronary syndrome patients

Chromosome 9 Risk Allele G Category Von Willebrand & Anticoagulant Proteins Tags Thrombosis, Blood Clotting, Cardiovascular, Heart Disease, Arrhythmia, Thrombophilia

ADAMTS13(https://www.ncbi.nlm.nih.gov/gene/11093) sits at the center of the VWF-platelet axis — a biological dial that determines whether platelet-rich microvascular thrombi form inappropriately. When ADAMTS13 activity is sufficient, it trims the hyper-adhesive VWF multimers released during vascular injury to safe...

rs2307449 Intronic variant in POLG (mitochondrial DNA polymerase gamma) on chromosome 15q26.1; the G allele is associated with earlier natural menopause by approximately 9–10 weeks per allele, implicated through mitochondrial DNA replication fidelity and oocyte energy metabolism

Chromosome 15 Risk Allele G Category Gamete Quality & DNA Repair Tags Fertility, Ovarian Reserve, Menopause, Mitochondria, DNA Repair, Aging

Every cell in the body contains hundreds to thousands of mitochondria, each carrying its own small circle of DNA — the mitochondrial genome(https://www.ncbi.nlm.nih.gov/gene/5428). Unlike nuclear DNA, which is replicated by a team of polymerases with redundant error-checking, mitochondrial DNA relies on a single...

rs2470890 Synonymous variant in CYP1A2 exon 7 in linkage disequilibrium with the *1F high-inducibility haplotype; carriers activate more heterocyclic amines and PAHs from cooked meat and smoke into DNA-damaging intermediates

Chromosome 15 Risk Allele T Category Cancer Risk Tags Cancer Risk, Carcinogen Metabolism, Detoxification, Caffeine, Smoking Interaction

Cytochrome P450 1A2 (CYP1A2) accounts for roughly 13% of all cytochrome P450 protein in the human liver and is the principal enzyme responsible for N-oxidation of heterocyclic amines (HCAs)(https://pubmed.ncbi.nlm.nih.gov/19838915/). This first metabolic step converts dietary HCAs like PhIP and MeIQxpyridine) and...

rs2681472 Intronic regulatory variant near the PMCA1 calcium pump gene, one of the most replicated blood pressure GWAS hits; the common A allele reduces calcium efflux efficiency in vascular cells, raising blood pressure ~1 mmHg per allele

Chromosome 12 Risk Allele A Category Blood Pressure & Hypertension Tags Cardiovascular, Blood Pressure, Hypertension, Salt Sensitivity, Calcium

Your blood vessels are in constant tension between vasoconstriction and relaxation, a balance governed in part by calcium. The ATP2B1 gene(https://omim.org/entry/108731). In vascular smooth muscle and cardiac endothelial cells, PMCA1 is essential for keeping intracellular calcium low enough to prevent chronic...

rs2736340 FAM167A-BLK region regulatory variant that reduces B-lymphoid tyrosine kinase expression and confers risk for the broadest autoimmune disease spectrum of any BLK locus SNP, including SLE, RA, SSc, primary Sjögren's syndrome, APS, myositis, and Kawasaki disease

Chromosome 8 Risk Allele T Category B-Cell Immunity & Antibody-Mediated Disease Tags Autoimmune, Lupus, Immune System, Immune & Autoimmune, B-Cell Signaling, Rheumatoid Arthritis

BLK (B-lymphoid tyrosine kinase)(https://www.ncbi.nlm.nih.gov/gene/640) encodes a kinase that drives B-cell activation and, crucially, enforces the self-tolerance checkpoint that eliminates self-reactive B-cell clones before they can generate pathogenic autoantibodies. rs2736340 sits within the FAM167A-BLK...

rs397508068 Pathogenic in-frame 3-bp deletion in the KCNQ1 potassium channel that removes phenylalanine-340 from the S6 transmembrane domain, impairing cardiac repolarization and causing Long QT syndrome type 1 with risk of torsades de pointes and sudden cardiac death

Chromosome 11 Risk Allele D Category Arrhythmia & Heart Rhythm Tags Arrhythmia, Cardiovascular, Heart Disease, Drug Response, Genetic Counseling

The heart beats reliably because each contraction is followed by a precisely timed electrical reset called cardiac repolarization(https://pubmed.ncbi.nlm.nih.gov/17470695/). The largest contributor to repolarization during exercise is the IKs current, carried by the potassium channel encoded by KCNQ1. When this...

rs4225 3'UTR variant that creates a microRNA-4271 binding site; the T allele suppresses APOC3 translation, lowering triglycerides and modestly reducing coronary heart disease risk

Chromosome 11 Risk Allele G Category Atherogenic Lipoproteins Tags Triglycerides, Cardiovascular, Lipid Metabolism, Fat Metabolism, Heart Disease, Inflammation

Apolipoprotein C-III (APOC3) is one of the body's most powerful brakes on fat clearance. This small protein, made in the liver and intestine, inhibits lipoprotein lipase and hepatic uptake of triglyceride-rich remnant particles(https://pubmed.ncbi.nlm.nih.gov/32849270/). When APOC3 levels are high, triglycerides...

rs4588 Alters vitamin D binding protein affinity, affecting total and bioavailable 25-hydroxyvitamin D levels

Chromosome 4 Risk Allele T Category Vitamin D Metabolism Tags Vitamin D, Bone Health, Cardiovascular, Diet, Mineral Metabolism

The GC gene encodes vitamin D binding protein (VDBP/DBP)(), the main transport protein for vitamin D metabolites in the blood. Nearly all circulating 25-hydroxyvitamin D — the form your doctor measures — travels bound to VDBP. A single nucleotide change at rs4588 swaps a threonine for a lysine at position 436 of the...