Research — GeneOps

rs12722489 Intronic variant in IL2RA intron 1 that creates an estrogen-responsive enhancer element — the risk C allele allows estrogen receptor alpha binding and increases IL2RA transcription, altering T-regulatory cell function and autoimmune disease susceptibility

Chromosome 10 Risk Allele C Category Autoimmune Tolerance & T-Cell Regulation Tags Immune & Gut, Immune & Autoimmune, Autoimmune, Type 1 Diabetes, Inflammation, Estrogen

The IL2RA gene(https://www.ncbi.nlm.nih.gov/gene/3559) sits at a critical junction of immune self-tolerance. CD25 is the defining surface marker of regulatory T cells(https://pubmed.ncbi.nlm.nih.gov/22461703/) (Tregs), and IL-2 signaling through the high-affinity receptor complex is the master signal for Treg...

rs12734494 Intergenic variant near SLC30A1 (ZnT1), the primary basolateral zinc exporter in intestinal enterocytes; the A allele is markedly less common in East Asian populations (7.6%) than in European (49.4%) or African (42.7%) populations, suggesting population-specific selective pressure on zinc transport efficiency.

Chromosome 1 Risk Allele A Category Vitamins & Nutrient Absorption Tags Zinc, Minerals, Micronutrients, Immune Function, Vitamins, Ancestry-Specific

Every milligram of zinc you absorb from food must cross two membranes in your intestinal cells. ZIP4 ferries zinc in from the gut lumen at the cell's apical face; ZnT1 (SLC30A1)(https://pubmed.ncbi.nlm.nih.gov/39422023/) then pumps it out the other side into the bloodstream. Without functional ZnT1, zinc is absorbed...

rs12740374 Regulatory variant that increases sortilin expression, lowering LDL cholesterol and cardiovascular risk

Chromosome 1 Risk Allele G Category Coronary Artery Disease & Atherosclerosis Tags Cholesterol, Cardiovascular, Lipid Metabolism, LDL Cholesterol, Heart Disease, Diet

Your chromosomes contain regulatory switches that control how much cholesterol circulates in your blood. At position 1p13.3 on chromosome 1, a single-letter DNA change creates or destroys a binding site for a protein called C/EBP(https://pubmed.ncbi.nlm.nih.gov/20686566/), fundamentally altering your liver's...

rs13193677 Intronic variant near the TRAF3IP2 locus (annotated in IPCEF1 at chr6q25.2 by dbSNP, 43 Mb distal) that was genotyped alongside TRAF3IP2 coding variants in SLE studies; the A allele is independently associated with SLE susceptibility (OR=1.73, P=0.046) and SLE pericarditis in the Ciccacci 2013 Italian cohort — completing the three-SNP TRAF3IP2/locus panel

Chromosome 6 Risk Allele A Category Psoriasis & Spondyloarthropathy Tags Immune & Gut, Autoimmune, Inflammation, Lupus, Cardiovascular

TRAF3IP2 encodes Act1 (also called CIKS — Connector of IKK and Stress-activated kinases), the essential adaptor protein for IL-17 receptor signaling (https://pubmed.ncbi.nlm.nih.gov/20953186/). While the most studied variants at this locus — D10N (rs33980500) and R74W (rs13190932) — affect the Act1 protein directly,...

rs1426654 Sodium/potassium/calcium exchanger that regulates melanin production in skin cells

Chromosome 15 Risk Allele A Category Skin & Eyes Tags Skin Pigmentation, Ancestry, Vitamin D, Sun Sensitivity, Melanoma Risk, UV Protection

A single letter change in the SLC24A5 gene — replacing alanine with threonine at position 111 of the protein — is the largest known contributor to lighter skin pigmentation in humans(https://pubmed.ncbi.nlm.nih.gov/16357253/). This variant alone explains 25-38% of the difference in skin melanin between people of...

rs150090666 Loss-of-function variant in phosphodiesterase 3B — carriers have enhanced cAMP-mediated lipolysis, higher HDL cholesterol, lower triglycerides, and reduced cardiovascular disease risk

Chromosome 11 Risk Allele T Category Triglycerides & Fatty Acids Tags Lipid Metabolism, Fat Distribution, Cardiovascular, HDL Cholesterol, Triglycerides, Metabolic

Your fat cells hold a carefully balanced switch between storing and releasing fat. Phosphodiesterase 3B (PDE3B) is the enzyme that applies the brake. It degrades cAMP(https://pubmed.ncbi.nlm.nih.gov/26031333/) in adipocytes. When PDE3B functions normally, it limits how strongly stress hormones like adrenaline can...

rs17249754 Intronic variant in the ATP2B1 calcium pump gene; the common G allele reduces PMCA1 expression in vascular tissue, impairing calcium efflux and raising blood pressure — one of the most replicated blood pressure GWAS loci across Asian and European populations

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

Running just 80 kilobases downstream of the widely-studied rs2681472 variant at the same gene, rs17249754 is an independent intronic variant in ATP2B1(https://omim.org/entry/108731). Like its neighboring variant, rs17249754 has reached genome-wide significance in multiple large international consortia, but its risk...

rs17266594 Intronic branch-point variant in BANK1 that shifts isoform balance toward full-length protein with intact TIR domain, amplifying TLR-driven B-cell activation and raising risk for SLE and systemic sclerosis

Chromosome 4 Risk Allele T Category B-Cell Immunity & Antibody-Mediated Disease Tags Autoimmune, Lupus, Immune System, Immune & Gut, B-Cell Signaling, TLR Signaling

BANK1 (B-cell scaffold protein with ankyrin repeats 1) is expressed almost exclusively in B cells, where it orchestrates two interconnected arms of immune signaling: B-cell receptor (BCR) activation(https://pubmed.ncbi.nlm.nih.gov/18204447/) and toll-like receptor (TLR)...

rs17881320 Intronic STAT3 variant associated with increased atopic dermatitis risk (OR=1.09) via altered cytokine signaling in the JAK-STAT pathway

Chromosome 17 Risk Allele T Category TNF, NF-kB & Inflammatory Cytokines Tags Autoimmune, Inflammation, Skin Health, Immune Response, Biologic Therapy

STAT3(https://www.ncbi.nlm.nih.gov/gene/6774) sits at the convergence point of nearly every inflammatory circuit driving atopic dermatitis. When cytokines dock on their receptors at the skin cell surface, receptor-associated JAK kinases(https://pubmed.ncbi.nlm.nih.gov/37536511/) phosphorylate STAT3, which then...

rs1800595 Factor V HR2 haplotype — a missense variant that mildly impairs the anticoagulant cofactor function of factor V; clinically significant mainly when co-inherited with Factor V Leiden, where the combination amplifies thrombotic risk 3- to 4-fold beyond Leiden alone

Chromosome 1 Risk Allele C Category Coagulation & Clotting Factors Tags Blood Clotting, Cardiovascular, Thrombophilia, Thrombosis, Blood Thinners

Coagulation Factor V is a large plasma protein with a dual role in hemostasis: it accelerates clot formation by amplifying thrombin generation, and it also assists activated protein C (APC) in switching off this cascade. The rs1800595 variant — known as the R2 polymorphism, H1299R, or the HR2 haplotype — subtly...