Research — GeneOps

rs12606138 Intronic variant in NEDD4L associated with reading ability and dyslexia susceptibility, within a gene that regulates ENaC sodium channel expression and blood pressure

Chromosome 18 Risk Allele A Category Blood Pressure & Hypertension Tags Brain Health, Cognition, Blood Pressure, Hypertension, Salt Sensitivity, Kidney Function

NEDD4L encodes an E3 ubiquitin protein ligase — an enzyme that tags specific proteins for degradation by labelling them with ubiquitin chains. Its most studied target is ENaC, the epithelial sodium channel(https://www.ncbi.nlm.nih.gov/gene/23327). NEDD4L ubiquitinates ENaC subunits, marking them for removal from the...

rs12688128 X-linked intronic variant in IL1RAPL2, a synaptic adhesion gene expressed exclusively in the central nervous system; carried as a haplotype associated with thyrotoxic hypokalaemic periodic paralysis in a Thai cohort, though this association was not replicated in a Korean population

Chromosome X Risk Allele A Category Endometriosis & Uterine Health Tags Fertility, Reproductive Health, Brain Health, Neurological Risk, Embryo Development, Male Fertility

IL1RAPL2(https://www.ncbi.nlm.nih.gov/gene/26280) is a member of the IL-1 receptor superfamily expressed almost exclusively in the central nervous system. Unlike most IL-1 receptor family members that participate in immune signaling, IL1RAPL2 functions as a synaptic adhesion...

rs12720356 A missense variant in the TYK2 pseudokinase (JH2) domain that partially impairs TYK2 catalytic regulation, reducing IL-12-stimulated STAT4 signaling and conferring independent protection against rheumatoid arthritis, psoriasis, SLE, and type 1 diabetes

Chromosome 19 Risk Allele A Category Autoimmune Tolerance & T-Cell Regulation Tags Autoimmune, JAK-STAT Signaling, Interferon, Inflammation, Psoriasis, Rheumatoid Arthritis

TYK2 is the most genetically validated drug target in autoimmune disease today. Its pseudokinase (JH2) domain — the regulatory scaffold that controls the adjacent catalytic domain — is a hotspot for naturally occurring protective variants that reduce IL-12, IL-23, and type I interferon signaling without eliminating...

rs13190932 Missense variant in the IL-17 adaptor Act1 (Arg74Trp) that is the primary GWAS hit for psoriatic arthritis at the TRAF3IP2 locus (OR=1.83, P=8.56×10⁻¹⁷); in strong LD with the functional D10N variant but appears to tag a partially overlapping, PsA-enriched haplotype

Chromosome 6 Risk Allele A Category Psoriasis & Spondyloarthropathy Tags Immune & Gut, Autoimmune, Inflammation, Psoriasis, Arthritis, Biologic Therapy

The TRAF3IP2 gene encodes Act1 (also called CIKS — Connection to IKK and Stress-activated protein kinase), the essential scaffolding protein(https://pubmed.ncbi.nlm.nih.gov/23116200/) in the IL-17 pathway. When genome-wide association studies scanned the locus looking for the single strongest statistical signal for...

rs13245639 Cis-regulatory IRF5 variant in near-perfect LD (r²=0.97) with the rs729302 protective haplotype; the T allele reduces IRF5 expression and shows allele-specific transcription factor binding in EMSA, making it a functional candidate and a high-quality WGS tag for the 5' protective haplotype block that dampens interferon-driven autoimmune susceptibility

Chromosome 7 Risk Allele C Category Interferon Signaling & Systemic Autoimmune Tags Immune & Autoimmune, Interferon, Lupus, Autoimmune, Connective Tissue, Inflammation

Your immune system's type I interferon alarm — orchestrated by Interferon Regulatory Factor 5 (IRF5) — is one of the most powerful switches in human innate immunity. When this switch runs too loud and too long, the result is chronic inflammatory damage seen in systemic lupus erythematosus, rheumatoid arthritis,...

rs13277113 Regulatory variant upstream of BLK that reduces B-lymphoid tyrosine kinase expression, impairing B-cell tolerance and raising risk for SLE, Sjögren's syndrome, systemic sclerosis, and rheumatoid arthritis

Chromosome 8 Risk Allele A Category B-Cell Immunity & Antibody-Mediated Disease Tags Autoimmune, Lupus, Immune System, Immune & Autoimmune, B-Cell Signaling, Rheumatoid Arthritis

BLK (B-lymphoid tyrosine kinase)(https://www.ncbi.nlm.nih.gov/gene/640) encodes a kinase that plays a critical role in B-cell receptor (BCR) signaling and B-cell development. Acting as an accelerator for BCR-driven activation signals, BLK helps B cells respond to antigen stimulation — but crucially, it also...

rs13702 LPL 3'UTR variant disrupting a microRNA-410 binding site; the C allele abolishes miR-410-mediated suppression of LPL mRNA, raising lipoprotein lipase activity and lowering plasma triglycerides

Chromosome 8 Risk Allele C Category Triglycerides & Fatty Acids Tags Triglycerides, HDL Cholesterol, Fat Metabolism, Cardiovascular, Omega-3

Lipoprotein lipase (LPL) is the principal enzyme that clears triglyceride-rich lipoproteins() from circulation. Most research into LPL genetics has focused on coding variants that change the protein itself. rs13702 works differently: it sits in the 3' untranslated region of the LPL gene, a stretch of mRNA that...

rs1408799 Intronic variant in the eumelanin enzyme TYRP1 associated with eye and hair color, UV sensitivity, and modestly elevated melanoma risk in Europeans

Chromosome 9 Risk Allele C Category Skin & Eyes Tags Pigmentation, Eye Color, Sun Sensitivity, Melanoma Risk, UV Protection

TYRP1 (tyrosinase-related protein 1) is a melanocyte-specific enzyme that sits at a critical junction in the eumelanin biosynthesis pathway. Inside melanosomes — the specialized organelles that produce and store pigment — TYRP1 catalyzes the oxidation of DHICA(https://pubmed.ncbi.nlm.nih.gov/7813420/), while...

rs17561 Missense variant in IL-1α (Ala114Ser) that acts as a common hypomorphic mutation — the minor Serine allele reduces IL-1α secretion by ~50% through post-translational retention; the Serine allele is associated with periodontitis susceptibility and ankylosing spondylitis in Europeans

Chromosome 2 Risk Allele A Category TNF, NF-kB & Inflammatory Cytokines Tags Autoimmune, Inflammation, Innate Immunity, Periodontal Disease, Arthritis, Immune System

Interleukin-1 alpha (IL-1α) is not just another pro-inflammatory cytokine — it is a unique alarmin(https://pubmed.ncbi.nlm.nih.gov/36175368/). Unlike IL-1β, which must be actively processed by the inflammasome and secreted, IL-1α is constitutively produced as a precursor (pro-IL-1α) in virtually all nucleated cells...

rs1799963 Second most common inherited thrombophilia; the A allele raises prothrombin levels by 30%, increasing venous thromboembolism risk 2-5 fold and is highly actionable for women considering oral contraceptives

Chromosome 11 Risk Allele A Category Coagulation & Clotting Factors Tags Blood Clotting, Cardiovascular, Thrombophilia, Women's Health, Blood Thinners

Prothrombin — also called coagulation Factor II — is the precursor to thrombin, the central enzyme that converts fibrinogen into fibrin clot. The G20210A mutation in the prothrombin gene (F2) doesn't change the structure of prothrombin itself; instead, it quietly turns up its production. Carriers make 30% more...