Research — GeneOps

rs547025 Intronic variant in SIRT3 (the principal mitochondrial deacetylase) associated with uterine fibroid risk; the common T allele is linked to modestly higher fibroid susceptibility while the rarer C allele appears protective, likely through effects on SIRT3 expression and mitochondrial oxidative-stress defence in uterine smooth muscle

Chromosome 11 Risk Allele T Category Endometriosis & Uterine Health Tags Uterine Fibroids, Fertility, Reproductive Health, Oxidative Stress, Women's Health, Mitochondria

Uterine fibroids (leiomyomas) affect an estimated 70–80% of women by age 50 and are among the leading indications for hysterectomy worldwide. The mechanisms underlying fibroid development involve a combination of estrogen sensitivity, dysregulated proliferation, and — increasingly recognised — oxidative stress and...

rs559406 Intronic PTPN2 variant whose G allele reduces T-cell protein tyrosine phosphatase (TC-PTP) activity, amplifying JAK-STAT signaling and conferring susceptibility to psoriasis and related autoimmune conditions

Chromosome 18 Risk Allele G Category Autoimmune Tolerance & T-Cell Regulation Tags Autoimmune, T-Cell Regulation, Inflammation, Immune & Autoimmune, Psoriasis, JAK-STAT Signaling

Every immune response needs a brake. T-cell protein tyrosine phosphatase — known as TC-PTP, encoded by PTPN2 — is one of the body's primary molecular brakes on the JAK-STAT signaling cascade(https://pubmed.ncbi.nlm.nih.gov/38707187/). The rs559406 variant is an intronic SNP in the PTPN2 gene on chromosome 18. Its G...

rs610604 Intronic variant in TNFAIP3 whose G allele is the primary psoriasis susceptibility signal at 6q23.3, tagging a regulatory haplotype distinct from the rheumatoid arthritis and lupus signals at the same locus, and predicting better response to TNF inhibitor therapy

Chromosome 6 Risk Allele G Category Psoriasis & Spondyloarthropathy Tags Autoimmune, Inflammation, Psoriasis, Anti-TNF Biologics, Immune & Gut, Skin

The TNFAIP3 gene at chromosome 6q23.3 encodes A20, the central negative regulator of NF-κB inflammatory signaling. Multiple independent genetic signals cluster at this locus, each tagging different disease susceptibilities and haplotypes — but not all signals confer the same risks. rs610604, an intronic variant...

rs61750591 A frameshift deletion in VWF that truncates von Willebrand factor from position 1649; heterozygous carriers are at risk for type 1 von Willebrand disease with reduced VWF levels and mucocutaneous bleeding, most prevalent in Northern European populations

Chromosome 12 Risk Allele D Category Von Willebrand & Anticoagulant Proteins Tags Blood Clotting, Cardiovascular, Carrier Status, Thrombophilia, Thrombosis

Von Willebrand factor is the molecular bridge between injury and clot. When a blood vessel tears, VWF multimers(https://pubmed.ncbi.nlm.nih.gov/10356656/) unspooling from the vessel wall snag passing platelets, holding them in place until a stable clot forms. Without enough VWF, platelets arrive but can't stick —...

rs72553883 Transmembrane domain missense variant in TACI that abolishes NF-κB signaling, impairing B-cell class switching and antibody production; associated with common variable immunodeficiency and selective IgA deficiency

Chromosome 17 Risk Allele T Category B-Cell Immunity & Antibody-Mediated Disease Tags B-Cell Signaling, Autoimmune, Immune Function, Infection Risk, Immune Response, Carrier Status, Innate Immunity, Immune System

TACI (Transmembrane Activator and CAML Interactor) is a receptor on B cells that functions as a critical switch for antibody class switching and the production of T-independent antibody responses. When TACI binds its natural ligands — BAFF and APRIL(https://pubmed.ncbi.nlm.nih.gov/19605846/) — it activates NF-κB...

rs727479 Intronic eQTL variant in the aromatase gene CYP19A1; the minor C allele is the strongest common genetic determinant of lower circulating estradiol in postmenopausal women, acting through altered aromatase expression in peripheral tissues.

Chromosome 15 Risk Allele C Category Reproductive Hormones Tags Aromatase, Estrogen Metabolism, Bone Health, Breast Cancer, Menopause, Estrogen

Estrogen doesn't come only from the ovaries. After menopause — and throughout life in men and premenopausal women — a substantial fraction of circulating estradiol is made locally in adipose tissue, bone, brain, and liver through the action of aromatase(https://www.ncbi.nlm.nih.gov/gene/1588). The amount of...

rs7305099 Intronic WNK1 variant where the G allele is associated with increased essential hypertension risk while the minor T allele is protective; WNK1 is the master kinase controlling renal sodium-chloride reabsorption through the NCC cotransporter

Chromosome 12 Risk Allele G Category Blood Pressure & Hypertension Tags Blood Pressure, Hypertension, Kidney Function, Cardiovascular, Salt Sensitivity, Renal Function

Blood pressure is ultimately a plumbing problem: the kidneys decide how much salt to keep and how much to excrete, and that decision sets the volume — and thus the pressure — of your blood. At the center of that decision is WNK1, a serine-threonine kinase expressed throughout the kidney's distal nephron that acts as...

rs73885316 Protective missense modifier in APOL1 that abolishes G2 risk allele cytotoxicity, strongly reducing kidney disease risk in carriers of G2-containing high-risk genotypes

Chromosome 22 Risk Allele A Category Uric Acid & Kidney Function Tags Kidney Disease, Kidney Function, Nephrology, Ancestry-Specific, Renal Function, Cardiovascular

The APOL1 gene encodes apolipoprotein L1(https://pubmed.ncbi.nlm.nih.gov/38036523/), a protein best known for its connection to chronic kidney disease in people of African ancestry. Two "risk haplotypes" — G1 and G2 — evolved to fight trypanosome parasites but cause focal segmental glomerulosclerosis...

rs763625913 Rare pathogenic nonsense variant in the LDL receptor gene that abolishes receptor function, causing receptor-negative familial hypercholesterolemia with severely elevated LDL-C and high premature coronary artery disease risk

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

The LDLR gene(https://omim.org/entry/606945) by binding apolipoprotein B-100 on LDL particles and shuttling them into cells for degradation. Without functional LDL receptors, circulating LDL accumulates relentlessly from birth — a condition called familial...

rs9277535 3' UTR eQTL that reduces HLA-DPB1 expression, impairing antigen presentation and increasing risk for chronic hepatitis B infection; also linked to multiple sclerosis and modulates rheumatoid arthritis risk through a dose-dependent trade-off in immune activation

Chromosome 6 Risk Allele G Category Interferon Signaling & Systemic Autoimmune Tags HLA, MHC Antigen Presentation, Immune & Antiviral, Immune & Autoimmune, Infection Risk, Autoimmune

HLA-DPB1 encodes the beta chain of the HLA-DP molecule, a class II MHC receptor that presents peptide antigens to CD4+ T helper cells. This is the essential handshake that triggers adaptive immunity: without robust HLA-DP surface expression, the immune system cannot efficiently recognize viral peptides and mount a...