Research — GeneOps

rs61750581 A2 domain missense variant in von Willebrand factor associated with type 2A von Willebrand disease; the proline substitution destabilizes the A2 domain, increasing susceptibility to ADAMTS13 proteolysis and depleting high-molecular-weight multimers required for platelet adhesion

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

Von Willebrand factor is not a single molecule but a polymer — its biological power comes from assembling into enormous high-molecular-weight multimers(https://pubmed.ncbi.nlm.nih.gov/41453393/) that can deploy across a damaged vessel wall and capture flowing platelets within microseconds. The A2 domain of VWF...

rs6445975 Intronic PXK variant; the G allele is a replicated GWAS risk allele for systemic lupus erythematosus in Europeans, acting through impaired receptor endocytosis and disrupted B-cell immune signalling

Chromosome 3 Risk Allele G Category B-Cell Immunity & Antibody-Mediated Disease Tags Lupus, Autoimmune, B-Cell Signaling, Inflammation, Immune System, T-Cell Regulation

PXK(https://pubmed.ncbi.nlm.nih.gov/18204446/) is a gene most people have never heard of — yet a variant within its intron has appeared consistently in genome-wide association scans for systemic lupus erythematosus (SLE) in European populations. The rs6445975 G allele was one of four loci with genome-wide...

rs6852441 Intronic SLC2A9 variant tagging a urate-transport regulatory haplotype; the protective T allele (~48% global frequency) is enriched in populations with lower gout prevalence and is associated with more efficient renal urate clearance, while the risk C allele — common in East Asians (~90%) where gout prevalence is highest — tags reduced GLUT9-mediated reabsorption efficiency and elevated serum uric acid

Chromosome 4 Risk Allele C Category Uric Acid & Kidney Function Tags Gout, Uric Acid, Cardiovascular, Diet, Kidney

Your kidneys filter roughly 70% of the uric acid your body excretes each day, and the SLC2A9 gene — encoding the GLUT9 transporter(https://pubmed.ncbi.nlm.nih.gov/18327257/) — is the single most important genetic regulator of how efficiently that process happens. rs6852441 is an intronic variant that tags a...

rs7167936 Intronic variant near the CYP19A1 promoter region, falling within MIR4713HG but mapping to the CYP19A1 RefSeqGene locus; associated with breast cancer histological grade and tumor size in a Swedish cohort, consistent with its position in the aromatase regulatory zone

Chromosome 15 Risk Allele G Category Reproductive Hormones Tags Aromatase, Estrogen, Breast Cancer, Fertility, Reproductive Health, Cancer Risk

Aromatase(https://www.ncbi.nlm.nih.gov/gene/1588) is expressed in the ovaries, adipose tissue, breast, bone, and brain. Local aromatase activity determines the estrogen microenvironment in hormone-sensitive tissues, and variants that alter CYP19A1 transcription or regulatory activity can shift the...

rs730882094 Rare likely-pathogenic missense variant in the LDLR EGF-like repeat domain causing impaired LDL receptor processing and familial hypercholesterolemia with severely elevated LDL-C and premature coronary artery disease risk

Chromosome 19 Risk Allele G Category Atherogenic Lipoproteins Tags Cardiovascular, LDL Cholesterol, Atherosclerosis, Heart Disease, Statins, Genetic Counseling

Every cell in your body needs cholesterol to build membranes and synthesize hormones. To keep blood LDL from accumulating, the LDLR gene(https://pubmed.ncbi.nlm.nih.gov/29219151/) encodes a receptor that acts like a molecular claw — binding LDL particles at the cell surface, pulling them inside, releasing the LDL...

rs7770370 Intronic tag SNP in HLA-DPB1 (and upstream of HLA-DPA1) that marks the HLA-DP haplotype controlling antigen-presenting cell surface expression; the G allele is strongly associated with chronic hepatitis B infection susceptibility and impaired hepatitis B vaccine antibody response across multiple populations

Chromosome 6 Risk Allele G Category Interferon Signaling & Systemic Autoimmune Tags HLA, Infectious Disease, Liver Disease, Vaccination, Immune & Antiviral, Immune Response

When the hepatitis B virus enters the body, the immune system must decide within weeks whether to mount a clearing response or allow the infection to persist for life. That decision hinges heavily on HLA class II antigen presentation(https://pubmed.ncbi.nlm.nih.gov/21346778/). rs7770370 sits within the HLA-DPB1 gene...

rs7852296 An intronic variant in the DENND1A locus on chromosome 9q33.3, a robustly replicated PCOS susceptibility region; the A allele tags regulatory variation that drives DENND1A overexpression in theca cells, elevating androgen biosynthesis

Chromosome 9 Risk Allele A Category Fertility & Ovarian Function Tags PCOS, Hormones, Fertility, Reproductive Health, Steroid Hormones, Testosterone

Deep inside ovarian theca cells, a protein better known for its role in cellular housekeeping has been implicated in one of the most common endocrine disorders in women of reproductive age. DENND1A(https://www.ncbi.nlm.nih.gov/gene/57706) sits at chromosome 9q33.3, a locus that genome-wide association studies have...

rs1342326 Regulatory variant upstream of IL33; the C allele elevates IL-33 expression, amplifying the alarmin signal through the ST2 receptor and raising susceptibility to asthma, allergic rhinitis, hay fever, and eosinophilic airway inflammation

Chromosome 9 Risk Allele C Category Allergy & Atopic Disease Tags Asthma, Inflammation, Innate Immunity, Autoimmune, Biologic Therapy, Lung Health

Beneath the surface of allergic asthma, rhinitis, and eczema lies a shared distress signal: IL-33(https://pubmed.ncbi.nlm.nih.gov/20860503/). rs1342326 sits approximately 25 kilobases upstream of the IL33 transcription start site on chromosome 9. The C allele acts as a gain-of-expression variant: carriers produce...

rs1532278 Intronic regulatory variant in CLU (clusterin/apolipoprotein J) that controls neuronal clusterin expression; the protective T allele elevates CLU transcription, enhancing amyloid-beta clearance across the blood-brain barrier and reducing Alzheimer's disease risk

Chromosome 8 Risk Allele C Category Neurology & Cognition Tags Alzheimer's, Brain Health, Neurodegeneration, Cognitive Decline, Neuroinflammation, Neuroprotection

Clusterin (CLU), also known as apolipoprotein J, is the third strongest known genetic risk factor for late-onset Alzheimer's disease after APOE and BIN1. It is a secreted molecular chaperone that binds misfolded proteins — including amyloid-beta (Aβ) — and escorts them out of the brain across the blood-brain...

rs1537373 Regulatory intronic variant within ANRIL (CDKN2B-AS1) at the 9p21.3 locus; the T risk allele is associated with substantially elevated risk of myocardial infarction, brain aneurysm, and type 2 diabetes through ANRIL-mediated dysregulation of cellular senescence and beta-cell proliferation

Chromosome 9 Risk Allele T Category Blood Sugar & Diabetes Tags Cardiovascular, Diabetes, Pancreatic Beta Cell, Atherosclerosis, Insulin, Cancer Risk

Deep inside chromosome 9 lies a short stretch of DNA — the 9p21.3 locus — that carries some of the most replicated disease associations ever discovered. Within this region sits ANRIL (antisense non-coding RNA in the INK4 locus), a long non-coding RNA that acts as a molecular volume knob for cellular senescence....