Research — GeneOps

rs35257264 Intronic variant near ST3GAL4 that modulates VWF and Factor VIII sialylation, slowing their hepatic clearance and raising plasma levels — an established independent VTE risk factor

Chromosome 11 Risk Allele T Category Coronary Artery Disease & Atherosclerosis Tags Blood Clotting, Thrombophilia, Cardiovascular, Thrombosis, Fibrinolysis

Your blood carries von Willebrand factor (VWF)(https://pubmed.ncbi.nlm.nih.gov/22530883/) and Factor VIII continuously, but the liver clears these proteins at a rate that determines their plasma concentration. What regulates clearance? In large part, a molecular sugar coating. Sialic acid residues attached to the...

rs3761847 Intronic GWAS variant in the TRAF1-C5 locus on chromosome 9 robustly associated with seropositive rheumatoid arthritis risk; the G allele tags a haplotype that upregulates TRAF1 expression and amplifies NF-kB-driven joint inflammation

Chromosome 9 Risk Allele G Category TNF, NF-kB & Inflammatory Cytokines Tags Autoimmune, Rheumatoid Arthritis, Inflammation, Anti-TNF Biologics, Immune & Autoimmune, Joints

Deep within the long arm of chromosome 9 sits a genetic locus that helps explain why rheumatoid arthritis clusters in families and why some patients respond poorly to the most effective treatments available. The TRAF1-C5 locus(https://pubmed.ncbi.nlm.nih.gov/17804836/) at 9q33.3 contains two genes, each contributing...

rs3789604 Synonymous RSBN1 variant that tags a PTPN22 locus haplotype independently associated with early-onset psoriasis, psoriatic arthritis risk, and Graves' disease susceptibility. Curator note — gene field stays RSBN1 (LD-block proximity), but the functional signal is at the PTPN22 locus; do not double-count with rs2476601 (PTPN22 R620W) when both appear in the same panel as they tag overlapping autoimmune risk.

Chromosome 1 Risk Allele G Category Autoimmune Tolerance & T-Cell Regulation Tags Autoimmune, Psoriasis, T-Cell Regulation, Immune System, Thyroid, Immune & Autoimmune

The PTPN22 gene region on chromosome 1p13 is one of the most studied loci in autoimmune genetics. Most attention focuses on the R620W missense variant (rs2476601), which alters T-cell signaling threshold and drives risk for rheumatoid arthritis, type 1 diabetes, and lupus. But haplotype analyses have revealed that...

rs3796508 Missense variant substituting valine with methionine at position 327 of TLR6, predicted damaging by SIFT and PolyPhen; the Met327 allele is rare globally but reaches 6% in East Asian populations and alters TLR2/TLR6 heterodimer function, affecting diacylated lipopeptide recognition from bacteria and mycoplasma with downstream consequences for innate immune regulation and autoimmune-inflammatory risk

Chromosome 4 Risk Allele T Category Innate Immunity & Infection Defense Tags Innate Immunity, Immune & Autoimmune, Inflammation, Bacterial Sensing, Immune System

Every time your immune cells encounter diacylated lipopeptides — the molecular calling-card of mycoplasma, staphylococcal lipoproteins, and certain gram-positive bacteria — they rely on a precise molecular handshake between Toll-like Receptor 2 (TLR2)(https://www.ncbi.nlm.nih.gov/gene/7097) and...

rs3877899 Missense variant in selenoprotein P that alters selenium transport capacity; the T allele (Thr234) is associated with lower circulating SELENOP levels after selenium intake and elevated risk of adverse outcomes in prostate cancer and retinopathy of prematurity

Chromosome 5 Risk Allele T Category Vitamins & Nutrient Absorption Tags Selenium, Antioxidants, Cancer Risk, Oxidative Stress, Micronutrients

Selenoprotein P (SELENOP, formerly SEPP1) is the primary selenium transport protein in human plasma. Unlike most proteins, which are built from the standard 20 amino acids, SELENOP incorporates selenocysteine(https://pubmed.ncbi.nlm.nih.gov/30008961/) at 10 positions. SELENOP accounts for roughly 50–60% of all...

rs3900940 Missense variant in MYH15 encoding a Thr1105Ala substitution in myosin heavy chain 15, associated with modest coronary heart disease and noncardioembolic stroke risk

Chromosome 3 Risk Allele C Category Cardiomyopathy & Structural Heart Tags Cardiovascular, Heart Disease, Atherosclerosis, Muscle, Thrombosis, Thrombophilia

Myosin heavy chains are the molecular motors that drive muscle contraction. The MYH gene family encodes 15 isoforms, each specialized for different muscle types: cardiac myosins power the heart, skeletal myosins drive limb movement, and a handful of unconventional isoforms serve more specialized roles. MYH15 falls...

rs4406273 Near-HLA-C intergenic variant that tags HLA-C*06:02 haplotype, conferring risk for early-onset psoriasis vulgaris through MHC class I antigen presentation

Chromosome 6 Risk Allele A Category Psoriasis & Spondyloarthropathy Tags Immune & Gut, HLA, Autoimmune, Skin Health, Inflammation, Immune System

The HLA-C gene sits at the heart of the immune system's antigen presentation machinery, producing the HLA-C protein that displays peptide fragments to CD8+ cytotoxic T cells(https://pubmed.ncbi.nlm.nih.gov/26621454/). One particular version of this protein — encoded by the HLA-C06:02 haplotype — is the strongest...

rs489693 Intergenic variant near MC4R with genome-wide significant association with antipsychotic-induced weight gain, particularly olanzapine and clozapine; also tags the MC4R locus for general BMI effects

Chromosome 18 Risk Allele A Category Appetite & Obesity Tags Appetite, Satiety, Obesity, Pharmacogenomics, Metabolic, Metabolic Syndrome

The melanocortin-4 receptor (MC4R) sits at the centre of the hypothalamus's appetite control system. When the brain releases satiety signals — leptin-driven alpha-melanocyte stimulating hormone() — MC4R receives them, suppressing hunger and raising energy expenditure. Rare coding mutations in MC4R cause severe...

rs498422 Intronic variant in TSBP1-AS1 (LOC101929163), a non-coding antisense RNA in the HLA region between TSBP1 and BTNL2 on chromosome 6p21.32; the G allele is associated with increased risk of non-obstructive azoospermia in Han Chinese men, with an odds ratio of approximately 1.42 in a large multi-stage GWAS

Chromosome 6 Risk Allele G Category Endometriosis & Uterine Health Tags Male Fertility, Fertility, HLA, Sperm Quality, Ancestry-Specific, Autoimmune

Non-obstructive azoospermia (NOA) is the complete absence of sperm in semen due to a failure of sperm production in the testes — the most severe form of male infertility, affecting roughly 1% of all men and approximately 10% of infertile men. Unlike obstructive azoospermia (where a physical blockage prevents sperm...

rs549476 Intronic NEDD4L variant influencing ubiquitin ligase isoform expression and salt-sensitive blood pressure regulation via the ENaC pathway

Chromosome 18 Risk Allele G Category Blood Pressure & Hypertension Tags Hypertension, Blood Pressure, Salt Sensitivity, Kidney Function, Cardiovascular, Heart Disease

In the collecting tubule of the kidney, a molecular handshake determines how much salt your body holds onto each day. The epithelial sodium channel (ENaC) sits at the apical membrane of tubular cells and controls the final step of sodium reabsorption. How long ENaC stays at the cell surface — and therefore how much...