Research — GeneOps

rs4562997 Second intronic enhancer variant in SMAD3 that modulates TGF-beta effector signaling in regulatory T cells, influencing susceptibility to autoimmune and inflammatory conditions including IBD and ankylosing spondylitis

Chromosome 15 Risk Allele A Category IBD & Mucosal Immunity Tags Autoimmune, T-Cell Regulation, Crohn's Disease, Gut Health, Inflammation, IBD

SMAD3 is the central intracellular signal transducer of TGF-beta (transforming growth factor-beta)(https://pubmed.ncbi.nlm.nih.gov/29083406/), the master pathway governing regulatory T cell (Treg) differentiation and immune tolerance. In immune cells, SMAD3 is required for Foxp3 expression — the transcription factor...

rs5029937 Intronic risk variant within TNFAIP3 intron 2 that independently increases susceptibility to rheumatoid arthritis and SLE through a distinct LD block from the nearby intergenic 6q23 signals, completing the three-signal risk model at the TNFAIP3 locus

Chromosome 6 Risk Allele T Category TNF, NF-kB & Inflammatory Cytokines Tags Autoimmune, Inflammation, Rheumatoid Arthritis, Immune & Gut, Lupus, Anti-TNF Biologics

The TNFAIP3 gene on chromosome 6q23 encodes A20, the primary negative regulator of NF-κB inflammatory signaling(https://pubmed.ncbi.nlm.nih.gov/19643665/). The 6q23 locus is one of the most replicated autoimmune susceptibility regions in the human genome, carrying three independently inherited risk signals that each...

rs61750612 Nonsense mutation creating a premature stop codon at position 1853 of von Willebrand factor; homozygotes develop severe type 3 VWD with essentially absent VWF and require factor replacement, while heterozygotes typically have mild type 1 VWD

Chromosome 12 Risk Allele A Category Von Willebrand & Anticoagulant Proteins Tags Blood Clotting, Cardiovascular, Carrier Status, Thrombophilia, Heart Disease

Von Willebrand factor (VWF) is a large glycoprotein that serves two essential roles in hemostasis: it acts as molecular glue that tethers platelets to damaged blood vessel walls, and it escorts coagulation factor VIII through the circulation, protecting it from premature breakdown. Without adequate VWF, even a minor...

rs6232 Missense variant in PCSK1 encoding an Asn221Asp substitution near the Ca-1 calcium binding site of prohormone convertase 1/3 (PC1/3); impairs catalytic activity by approximately 10%, reducing cleavage of proinsulin to insulin, POMC to alpha-MSH, and proglucagon to GLP-1; the strongest functionally-characterized common PCSK1 coding variant, with OR 1.15 for obesity in meta-analysis of over 331,000 individuals across multiple ethnic groups

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

Deep inside your pancreatic beta cells, hypothalamic neurons, and intestinal L cells, a serine protease called PC1/3(https://pubmed.ncbi.nlm.nih.gov/18604207/) performs the molecular surgery that turns inactive prohormone precursors into working hormones. It cuts proinsulin into insulin, cleaves POMC into the...

rs6557160 Intergenic 6q25.1 variant between CCDC170 and ESR1; the C allele is an eQTL for CCDC170 expression and is associated with breast cancer risk, bone density, and estrogen-sensitive tissue proliferation

Chromosome 6 Risk Allele C Category Endometriosis & Uterine Health Tags Endometriosis, Estrogen, Estrogen Metabolism, Breast Cancer, Bone Health, Women's Health

The 6q25.1 region on chromosome 6 is one of the most genetically complex and biologically important loci in estrogen-sensitive tissue biology. It encodes estrogen receptor alpha (ERα)(https://pubmed.ncbi.nlm.nih.gov/26928228/) and the adjacent coiled-coil domain containing protein 170 (CCDC170), whose precise...

rs6887695 Upstream regulatory variant ~60 kb 5' of IL12B, forming the canonical two-SNP psoriasis risk haplotype with rs3212227 (3'-UTR); C allele elevates IL-12/IL-23 p40 expression, increasing psoriasis, psoriatic arthritis, and IBD susceptibility

Chromosome 5 Risk Allele C Category Psoriasis & Spondyloarthropathy Tags Immune & Autoimmune, Psoriasis, Inflammation, Inflammatory Bowel Disease, Biologic Therapy, Skin

The IL12B gene(https://www.omim.org/entry/161561). IL-12 drives Th1 differentiation, IFN-γ production, and antimicrobial immunity; IL-23 expands Th17 cells and IL-17 production, sustaining chronic skin and gut inflammation. Both pathways converge on psoriatic disease — IL-12/Th1 activates keratinocytes via IFN-γ,...

rs7234029 Intronic PTPN2 variant that reduces expression of T-cell protein tyrosine phosphatase (TC-PTP), lowering the threshold for JAK/STAT-driven T-cell activation and increasing susceptibility to Crohn's disease, rheumatoid arthritis, and juvenile idiopathic arthritis

Chromosome 18 Risk Allele G Category Autoimmune Tolerance & T-Cell Regulation Tags T-Cell Regulation, Inflammation, IBD, Crohn's Disease, Autoimmune, Rheumatoid Arthritis

Inside every T-cell, a molecular brake pedal controls how aggressively the cell responds to immune activation signals. That brake is TC-PTP (T-cell protein tyrosine phosphatase)(https://pubmed.ncbi.nlm.nih.gov/32652144/). When TC-PTP functions at full strength, it restrains T-cell activation to a level proportional...

rs760695410 Pathogenic missense variant in CYP17A1 disrupting the heme-binding region of the enzyme, abolishing both 17α-hydroxylase and 17,20-lyase activity; the most common CYP17A1 mutation in East Asian populations (Chinese, Japanese, Korean); homozygotes develop combined 17α-hydroxylase/17,20-lyase deficiency with cortisol deficiency, sex steroid absence, and mineralocorticoid excess causing hypertension

Chromosome 10 Risk Allele A Category Reproductive Hormones Tags Steroid Hormones, Steroid Metabolism, Hypertension, Reproductive Health, Carrier Status, Congenital

CYP17A1(https://pubmed.ncbi.nlm.nih.gov/26862015/) encodes the single enzyme responsible for two consecutive reactions that are essential for all downstream steroid hormone production. The rs760695410 variant (c.1118AT, p.His373Leu) is a missense change that destroys CYP17A1 function and, in homozygous individuals,...

rs7660895 Intronic variant in the major renal urate transporter GLUT9; the G allele reduces renal urate excretion, raising serum uric acid and increasing gout risk, with stronger effects in women than men

Chromosome 4 Risk Allele G Category Uric Acid & Kidney Function Tags Uric Acid, Gout, Kidney, Micronutrients, Diet, Kidney Function

Every day, your kidneys filter almost the entire blood volume of uric acid and then reabsorb roughly 90% of it back into the bloodstream. The protein that does most of this reabsorption — GLUT9, encoded by SLC2A9(https://pubmed.ncbi.nlm.nih.gov/18327257/) — is the dominant gatekeeper of serum urate levels. Intronic...

rs7951 Synonymous C3 variant associated with reduced serum complement C3 levels and increased risk for systemic lupus erythematosus through impaired complement-mediated immune complex clearance

Chromosome 19 Risk Allele A Category B-Cell Immunity & Antibody-Mediated Disease Tags Complement System, Lupus, Autoimmune, Inflammation, Kidney Disease, Immune Function

The complement system is one of the immune system's oldest defense mechanisms — a cascade of proteins that coat pathogens, signal immune cells, and clear cellular debris and immune complexes from the circulation. Complement C3(https://pubmed.ncbi.nlm.nih.gov/18174230/) is the most abundant complement protein in...