Research — GeneOps

rs61752717 The most common and clinically severe MEFV mutation, converting methionine to valine at codon 694 of pyrin; homozygous carriers typically develop full familial Mediterranean fever with early onset, frequent attacks, and high amyloidosis risk if untreated with colchicine

Chromosome 16 Risk Allele C Category TNF, NF-kB & Inflammatory Cytokines Tags Autoimmune, Inflammation, Amyloidosis, Carrier Status, Innate Immunity, Arthritis

Familial Mediterranean fever (FMF) is the most common hereditary inflammatory disease in the world, driven by mutations in the MEFV gene that encodes pyrin(https://pubmed.ncbi.nlm.nih.gov/31589380/). Of the hundreds of MEFV variants described, M694V stands apart: it is simultaneously the most prevalent pathogenic...

rs6235 Missense variant encoding the Ser690Thr substitution in the C-terminal domain of prohormone convertase 1/3 (PC1/3); paired with rs6234 (Q665E) in near-complete LD to form the Q665E-S690T haplotype that reduces PC1/3 enzymatic efficiency, impairing proinsulin-to-insulin conversion and POMC processing to satiety peptides, and conferring modest obesity risk

Chromosome 5 Risk Allele G Category Appetite & Obesity Tags Insulin, Obesity, Appetite, Pancreatic Beta Cell, Energy Metabolism, Metabolic

Every time your pancreatic beta cells sense rising blood glucose, they do not release insulin directly — they release proinsulin(https://pubmed.ncbi.nlm.nih.gov/20534142/), a folded precursor that needs enzymatic cutting to become active. The enzyme responsible for most of that cleavage is prohormone convertase 1/3...

rs71575922 An intronic variant in SYNE1 (Nesprin-1) at the 6q25.1 locus, first identified as a genome-wide significant endometriosis locus in the 2017 Sapkota meta-analysis and confirmed in the 2023 Rahmioglu mega-GWAS; the G allele is associated with endometriosis risk overall (OR ~1.11) and strongly enriched for pain subphenotypes including dysmenorrhea (OR ~1.49) and dyspareunia (OR ~2.07), implicating a neuromechanical rather than purely hormonal pathway

Chromosome 6 Risk Allele G Category Endometriosis & Uterine Health Tags Endometriosis, Pain Management, Chronic Pain, Women's Health, Reproductive Health, Fertility

Endometriosis affects roughly 1 in 10 women of reproductive age, yet the severity of pain symptoms varies enormously among those who carry the disease. A woman with minimal lesion burden may be disabled by pain, while another with extensive disease reports few symptoms. The emerging explanation for this paradox lies...

rs72634030 Intronic RABEP1 variant associated with rheumatoid arthritis risk, acting through endosomal trafficking and autophagy pathways that regulate antigen processing in immune cells

Chromosome 17 Risk Allele T Category Autoimmune Tolerance & T-Cell Regulation Tags Autoimmune, Rheumatoid Arthritis, Immune & Autoimmune, Innate Immunity, Inflammation, Autoimmunity

Your immune system's ability to distinguish self from foreign depends on an intricate molecular sorting system inside immune cells. Antigens captured from the environment must travel through a chain of membrane-bound compartments called endosomes before fragments are loaded onto MHC class II molecules and displayed...

rs7540214 Intronic variant in the interferon lambda receptor 1 gene that elevates PsA risk by amplifying IL-29/IFN-lambda signaling in synovial tissue, marking those with skin psoriasis who are at elevated risk for progressing to joint disease

Chromosome 1 Risk Allele T Category Psoriasis & Spondyloarthropathy Tags Interferon, Psoriasis, Arthritis, Immune & Autoimmune, Joints, Bone & Joint

Most people with psoriasis never develop joint disease. But roughly 30% do — and predicting who is at risk before joint damage begins is one of the central challenges in psoriatic disease management. The rs7540214 variant sits in the IFNLR1 gene, which encodes the interferon lambda receptor...

rs77924615 Intronic regulatory variant physically located in PDILT that controls uromodulin (Tamm-Horsfall protein / UMOD) expression — the strongest genetic predictor of longitudinal kidney function decline in the general population. Catalog gene attribution is UMOD (the regulatory target and clinically relevant gene); physical location is PDILT (adjacent gene in the same LD block).

Chromosome 16 Risk Allele G Category Uric Acid & Kidney Function Tags Kidney Disease, Kidney Function, Hypertension, Blood Pressure, Cardiovascular, Chronic Kidney Disease

Uromodulin, encoded by the UMOD gene, is the most abundant protein in normal human urine. Produced exclusively by cells lining the thick ascending limb of Henle's loop(), uromodulin forms protective filaments that trap bacteria, regulate sodium transport, and modulate the immune environment of the urinary tract. How...

rs858518 Intronic variant within the SHBG gene that participates in a haplotype (with rs727428) lowering circulating sex hormone-binding globulin levels, increasing bioavailable testosterone and estradiol; lower SHBG is linked to PCOS susceptibility, insulin resistance, type 2 diabetes risk, and female VTE risk mediated by estradiol

Chromosome 17 Risk Allele A Category Reproductive Hormones Tags Testosterone, Estrogen, Fertility, Reproductive Health, PCOS, Insulin Resistance, Hormones

Sex hormone-binding globulin (SHBG) is a critical gatekeeper for sex hormone action throughout the body. Only 1–2% of testosterone and estradiol circulate as free, bioactive hormones — the rest is bound to SHBG (about 44%) or albumin. The SHBG gene on chromosome 17 encodes this protein, and variants within it...

rs9332739 Missense variant in complement component C2 forming a protective haplotype with CFB that reduces age-related macular degeneration risk by ~45-50%

Chromosome 6 Risk Allele G Category B-Cell Immunity & Antibody-Mediated Disease Tags Eye Health, Complement System, Inflammation, Aging, Autoimmune

Complement component C2 is a serine protease that sits at the entry point of the classical complement pathway(https://pubmed.ncbi.nlm.nih.gov/26941740/). When the pathway fires, C2 is cleaved to form the C4b2a complex — the classical C3 convertase — which drives opsonisation, inflammatory signalling, and membrane...

rs16947078 Intergenic regulatory variant near TBX21 associated with allergic asthma susceptibility; G allele homozygosity carries markedly elevated asthma risk through reduced T-bet-driven Th1 immune tone

Chromosome 17 Risk Allele G Category Allergy & Atopic Disease Tags Autoimmune, Asthma, Immune Function, T-Cell Regulation, Inflammation, Lung Health

Inside every T cell stands a molecular fork in the road: become a Th1 cell or a Th2 cell. T-bet(https://pubmed.ncbi.nlm.nih.gov/12938094/) is the master regulator of that decision. When T-bet is abundant and active, naive T cells commit to the Th1 path — driving antiviral, antibacterial immunity and suppressing...

rs17651213 Intronic MAPT variant that directly regulates tau exon 3 splicing via differential hnRNP F/Q binding; the G allele (H1 haplotype) reduces exon 3 inclusion, elevating 4-repeat tau isoforms and increasing risk for Parkinson's disease, PSP, and corticobasal degeneration

Chromosome 17 Risk Allele G Category Neurology & Cognition Tags Neurological Risk, Parkinson's, Dementia, Tau Pathology, Brain Health, Aging

Within the MAPT gene on chromosome 17, the rs17651213 variant sits in a functionally critical position: it is one of just two intronic polymorphisms that directly control how much tau protein includes its N-terminal exon 3 domain. While the broader H1/H2 haplotype distinction at MAPT has been recognized as a major...