Research — GeneOps

rs2251780 Intronic variant in the glutathione reductase gene affecting antioxidant defense; the minor A allele has been associated with poorer recovery after sudden sensorineural hearing loss treated with corticosteroids, consistent with impaired cochlear oxidative stress clearance

Chromosome 8 Risk Allele A Category Vitamins & Nutrient Absorption Tags Antioxidants, Oxidative Stress, B Vitamins, Glutathione, Hearing Loss, Sensorineural, Glutathione Cycle, NRF2 Target

Glutathione reductase (GSR) is the enzyme that closes the glutathione antioxidant cycle: it uses NADPH and the cofactor flavin adenine dinucleotide (FAD, derived from riboflavin/vitamin B2) to regenerate reduced glutathione (GSH) from oxidized glutathione (GSSG). Without functioning GSR, oxidative damage accumulates...

rs2275913 Promoter variant in the NFAT binding site that increases IL-17A transcription, elevating Th17-driven inflammation and autoimmune disease risk

Chromosome 6 Risk Allele A Category TNF, NF-kB & Inflammatory Cytokines Tags Immune & Gut, Immune & Autoimmune, Inflammation, Autoimmune, Vitamin D, Omega-3

Interleukin-17A (IL-17A) is the signature cytokine of Th17 cells(https://pubmed.ncbi.nlm.nih.gov/22028838/). Under normal conditions, Th17 cells defend against extracellular bacteria and fungi; when dysregulated, they become primary drivers of autoimmune inflammation in psoriasis, rheumatoid arthritis, ankylosing...

rs2303369 Intronic variant in FNDC4 (fibronectin type III domain containing 4) on chromosome 2; the T allele is associated with earlier age at natural menopause and increased risk of primary ovarian insufficiency through disruption of follicular granulosa cell signaling.

Chromosome 2 Risk Allele T Category Fertility & Ovarian Function Tags Ovarian Reserve, Menopause, Fertility, Reproductive Health, Hormones, DNA Repair

Your body's reproductive clock is partly set by genes long before you are born. Among the loci robustly linked to the timing of natural menopause and the risk of primary ovarian insufficiency (POI) is rs2303369, an intronic variant in the FNDC4(https://pubmed.ncbi.nlm.nih.gov/35521900/) gene on chromosome 2. The T...

rs231775 Missense variant in the CTLA-4 leader peptide that reduces surface expression of this immune checkpoint receptor, increasing T cell activity and autoimmune disease risk

Chromosome 2 Risk Allele G Category Autoimmune Tolerance & T-Cell Regulation Tags Immune & Autoimmune, Autoimmune, Thyroid, Type 1 Diabetes, Lupus, Inflammation

CTLA-4 (Cytotoxic T-Lymphocyte Associated Protein 4) is one of the immune system's most powerful brakes. Expressed on activated T cells, it competes with CD28 to bind CD80 and CD86 on antigen- presenting cells — and when CTLA-4 wins, T cell activation is dampened. The rs231775 variant (also called +49AG or Thr17Ala)...

rs27044 Missense variant in the ERAP1 C-terminal regulatory domain modulating peptide trimming length-selectivity; Gln730 (G allele, risk) is part of hyperactive ERAP1 haplotypes that over-trim peptides for HLA class I presentation, increasing ankylosing spondylitis susceptibility in HLA-B27 carriers

Chromosome 5 Risk Allele G Category Psoriasis & Spondyloarthropathy Tags Immune System, Autoimmune, Inflammation, Arthritis, MHC Antigen Presentation, Psoriasis

The immune system's ability to distinguish self from non-self depends on an exquisitely precise editing process deep inside every nucleated cell. ERAP1 (Endoplasmic Reticulum Aminopeptidase 1)(https://pubmed.ncbi.nlm.nih.gov/23733883/) acts as a molecular ruler, measuring and calibrating the peptide repertoire...

rs28647808 Missense variant in the spacer domain of ADAMTS13 that reduces VWF-cleaving protease activity and, in type 2 diabetics, increases renal and cardiovascular complication risk with preferential benefit from ACE inhibitor therapy

Chromosome 9 Risk Allele G Category Von Willebrand & Anticoagulant Proteins Tags Thrombosis, Cardiovascular, Blood Clotting, Diabetes, Kidney Disease, Heart Disease, Thrombophilia

Your blood contains a molecular scissors called ADAMTS13(https://pubmed.ncbi.nlm.nih.gov/23733198/), a protease whose sole critical job is to cut ultra-large von Willebrand factor (VWF) multimers into smaller, manageable pieces. Without this cleavage, VWF multimers accumulate in circulation and on vessel walls,...

rs2883929 Intronic variant in the mineralocorticoid receptor gene associated with altered receptor signaling and modestly elevated risk of spontaneous preterm birth; the minor G allele shows protective effects are reduced compared to the common A allele

Chromosome 4 Risk Allele G Category Reproductive Hormones Tags Reproductive Health, Fertility, Stress Response, Blood Pressure, Hormones, Women's Health

The mineralocorticoid receptor (MR), encoded by NR3C2, is far more than a blood-pressure sensor. It binds aldosterone and cortisol to coordinate sodium retention, potassium excretion, and fluid homeostasis in the kidneys — but the same receptor is also expressed in the uterus, placenta, and vascular endothelium,...

rs2976388 Intronic PSCA variant that tags a regulatory region active in bladder urothelium; the G allele is associated with increased UTI frequency in women and with peptic ulcer disease susceptibility

Chromosome 8 Risk Allele G Category Innate Immunity & Infection Defense Tags Infection Risk, Innate Immunity, Bladder Cancer, Women's Health, Immune Defense, Gut Health

PSCA(https://www.ncbi.nlm.nih.gov/gene/8000) lines the inner surface of the bladder and is thought to help maintain urothelial integrity against bacterial attachment. The rs2976388 variant sits deep within an intron of the PSCA gene at chromosome 8, position 142,678,838 (GRCh38). It does not change the protein...

rs3131379 Intronic variant in the HLA class III region near MSH5 associated with lupus susceptibility, IFN-α regulation, and epistatic interactions with IRF5 and CTLA4

Chromosome 6 Risk Allele A Category Interferon Signaling & Systemic Autoimmune Tags Immune & Autoimmune, Lupus, Interferon, Autoimmune, Inflammation, Connective Tissue

The chromosome 6p21.33 locus is one of the most gene-dense and immunologically consequential stretches in the human genome. Wedged between the classical HLA genes and the complement cascade genes C2 and CFB lies the HLA class III region(https://pubmed.ncbi.nlm.nih.gov/22233601/), and within it, MSH5 (MutS Homolog...

rs35318931 X-linked extracellular matrix variant affecting skin connective tissue integrity and stretch mark susceptibility

Chromosome X Risk Allele A Category Skin & Eyes Tags Skin & Eyes, Connective Tissue, Extracellular Matrix, Collagen

When your skin stretches rapidly — during growth spurts, pregnancy, or weight change — the dermal connective tissue can tear, producing striae distensae (https://pubmed.ncbi.nlm.nih.gov/23633020/). Whether you develop visible stretch marks depends partly on your genes. The SRPX gene encodes a sushi-repeat-containing...