Research — GeneOps

rs200482978 Pathogenic nonsense variant in the intestinal zinc transporter ZIP4, creating a premature stop codon (p.Trp401Ter) that abolishes ZIP4 function and causes autosomal recessive acrodermatitis enteropathica when inherited biallelically; heterozygous carriers retain adequate zinc absorption under normal conditions but warrant monitoring during high-demand states

Chromosome 8 Risk Allele T Category Iron & Mineral Transport Tags Zinc, Minerals, Micronutrients, Digestive Health, Skin Health, Carrier Status

Every milligram of zinc your body uses must be freshly absorbed from food — there are no meaningful zinc stores to fall back on. The gateway is a twelve-pass transmembrane protein called ZIP4(), expressed densely on the absorptive face of duodenal enterocytes. When ZIP4 is missing or non-functional, dietary zinc...

rs201408742 X-linked intergenic variant near GPR174 (G protein-coupled receptor 174), a lysophosphatidylserine receptor expressed in lymphoid tissues; associated with modest rheumatoid arthritis risk, part of a GWAS signal at the GPR174/Xq21.1 locus

Chromosome X Risk Allele A Category TNF, NF-kB & Inflammatory Cytokines Tags Autoimmune, Rheumatoid Arthritis, Inflammation, T-Cell Regulation, Immune Function, Ancestry-Specific

On the X chromosome at band Xq21.1 sits a gene that the immune system relies on to tune the behaviour of T cells and dendritic cells: GPR174 (G protein-coupled receptor 174)(https://www.ncbi.nlm.nih.gov/gene/84636). GPR174 encodes a seven-transmembrane GPCR expressed at high levels in lymph nodes, appendix, and...

rs2070699 Intronic EDN1 variant modulating endothelin-1 expression; the T allele associates with elevated ET-1 levels, increased risk of persistent pulmonary hypertension of the newborn, aneurysm rebleeding after subarachnoid hemorrhage, and altered nitric oxide metabolism in women

Chromosome 6 Risk Allele T Category Blood Pressure & Hypertension Tags Cardiovascular, Blood Pressure, Nitric Oxide, Thrombosis, Arrhythmia, Heart Disease, Thrombophilia

Endothelin-1 (ET-1), encoded by the EDN1 gene on chromosome 6, is the most potent endogenous vasoconstrictor known. It is produced primarily by vascular endothelial cells and acts on smooth muscle to contract blood vessels, regulate blood pressure, and modulate vascular tone across virtually every major vascular bed...

rs216311 Missense variant in VWF at codon 1381 (Thr→Ala); the Ala allele (C on plus strand) is the global majority allele and is associated with higher circulating von Willebrand factor levels and elevated thrombotic risk

Chromosome 12 Risk Allele C Category Von Willebrand & Anticoagulant Proteins Tags Thrombosis, Blood Clotting, Cardiovascular, Thrombophilia, Venous Health, Heart Disease

Von Willebrand factor(https://pubmed.ncbi.nlm.nih.gov/30246494/) is one of the most potent modulators of bleeding and thrombosis risk in the human genome. Plasma VWF levels vary enormously between individuals — roughly four-fold from the 1st to the 99th percentile — and that variation is substantially heritable. The...

rs2228000 Missense variant in the DNA damage recognition gene XPC that moderately reduces nucleotide excision repair capacity, with elevated risk for bladder and breast cancer, particularly in homozygous carriers and those with carcinogen exposure

Chromosome 3 Risk Allele A Category Cancer Risk Tags Cancer Risk, DNA Repair, Bladder Cancer, Breast Cancer, Smoking Interaction, Cancer Screening

Every day your cells cope with thousands of DNA lesions — from ultraviolet light, environmental carcinogens, and byproducts of normal cellular metabolism. The XPC protein is the first responder in the global-genome nucleotide excision repair pathway(https://pubmed.ncbi.nlm.nih.gov/23400628/). Without efficient XPC...

rs2248932 Intronic BLK variant in the FAM167A-BLK regulatory locus that reduces B-lymphoid kinase expression and independently raises risk for systemic lupus erythematosus and related autoimmune diseases

Chromosome 8 Risk Allele A 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) is the kinase that drives B-cell receptor (BCR) signaling and enforces the central tolerance checkpoint that eliminates self-reactive B cells. rs2248932 sits in intron 1 of BLK within the FAM167A-BLK regulatory locus on chromosome 8p23.1 — the...

rs2296241 Synonymous coding variant in CYP24A1 (vitamin D 24-hydroxylase) that tags functional haplotypes influencing vitamin D catabolism efficiency and cancer susceptibility

Chromosome 20 Risk Allele G Category Vitamin D Metabolism Tags Vitamin D, Cancer Risk, Liver Disease, Metabolic, Immune Function, Mineral Metabolism

Your body's vitamin D system depends not just on how much vitamin D you take in, but on how fast your cells break it down. CYP24A1() is the primary off-switch for active vitamin D signaling, expressed in virtually every vitamin D-responsive tissue. The variant rs2296241 is a synonymous coding change() (c.552CT,...

rs2303729 Missense variant in LTBP4 encoding Val194Ile; the A allele (Ile) forms the IAAM haplotype that binds latent TGF-β1 with higher avidity, reducing free TGF-β signaling and acting as a protective modifier of Duchenne muscular dystrophy severity — IAAM homozygotes retain ambulation approximately 1.8 years longer than VTTT carriers under glucocorticoid treatment

Chromosome 19 Risk Allele G Category Gamete Quality & DNA Repair Tags Fibrosis, Muscle, Muscle Development, Cardiovascular, Connective Tissue, Fitness

Latent TGF-β-binding protein 4 (LTBP4) is a structural component of the extracellular matrix that performs two intertwined jobs: it scaffolds elastic fibers in connective tissue and captures latent TGF-β1(https://www.ncbi.nlm.nih.gov/gene/7040), holding it in an inert reservoir until controlled release. rs2303729 is...

rs2968863 Intergenic variant near KCNH2 (hERG potassium channel) at 7q36.1 that shortens QTc interval and confers ~2.4x increased risk of early-onset lone atrial fibrillation in homozygous T allele carriers

Chromosome 7 Risk Allele T Category Arrhythmia & Heart Rhythm Tags Arrhythmia, Cardiovascular, Heart Disease, Genetic Counseling

The KCNH2 gene encodes Kv11.1, more commonly known as the hERG potassium channel(https://pubmed.ncbi.nlm.nih.gov/18222980/). IKr is essential for terminating each heartbeat — it drives the electrical return from depolarization, setting the QTc interval and determining how quickly the heart is ready for the next...

rs2972164 Intronic PPARG variant associated with rate of change in insulin sensitivity over time, independent of adiposity

Chromosome 3 Risk Allele T Category Liver Fat Tags Fat Metabolism, Insulin, Insulin Resistance, Metabolic, Diabetes, Lipid Metabolism

PPARG() governs how your body creates fat cells and regulates their function. It is the molecular target of thiazolidinedione| thiazolidinediones (TZDs): a class of insulin-sensitizing drugs including pioglitazone and rosiglitazone that work by binding and activating PPARG drugs used in type 2 diabetes treatment,...