Research — GeneOps

rs5029939 Intronic variant near TNFAIP3 that tags a 6q23 haplotype strongly associated with SLE and Sjogren's syndrome through impaired A20 ubiquitin-editing activity and NF-kB dysregulation

Chromosome 6 Risk Allele G Category TNF, NF-kB & Inflammatory Cytokines Tags Autoimmune, Inflammation, Lupus, Gut Barrier, Immune & Gut, Sjögren's

Deep in chromosome 6, within an intron of the TNFAIP3 gene, lies a variant that marks one of the strongest known single-SNP associations with systemic lupus erythematosus. The rs5029939 G allele does not change the A20 protein's amino acid sequence — instead, it tags a haplotype at the 6q23 locus that alters how...

rs61750630 Pathogenic missense variant in von Willebrand factor causing intracellular retention of the mutant protein; homozygosity causes severe type 3 von Willebrand disease, heterozygous carriers typically have reduced VWF levels and mild bleeding symptoms

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

Von Willebrand factor is the molecular glue of hemostasis: a multimeric glycoprotein that captures platelets at the site of a vascular injury and shuttles factor VIII through the bloodstream. Without adequate VWF activity, even minor cuts fail to clot properly and surgical bleeding can become life-threatening. The...

rs6234 Missense variant in PCSK1 that causes a Gln665Glu substitution in the C-terminal domain of prohormone convertase 1/3 (PC1/3), reducing enzyme activity and impairing cleavage of proinsulin to insulin, POMC to alpha-MSH, and proglucagon to GLP-1; the first of a near-obligate coding haplotype (Q665E/S690T, rs6234/rs6235) associated with modest but well-replicated obesity risk across European populations

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

Inside your pancreas, gut, and hypothalamus sits a molecular enzyme that is essential for activating three of the most important metabolic hormones in your body. Prohormone convertase 1/3 (PC1/3) (https://pubmed.ncbi.nlm.nih.gov/27187081/) cuts proinsulin into insulin, cleaves POMC into the satiety peptide...

rs6757908 Rare intronic variant in EIF2AK3-AS1, an antisense long non-coding RNA that regulates expression of EIF2AK3 (PERK), the kinase mediating the endoplasmic reticulum unfolded protein response; PERK pathway activation is documented in endometriotic tissue, linking ER stress to ectopic lesion survival and ovarian damage in endometriosis

Chromosome 2 Risk Allele G Category Endometriosis & Uterine Health Tags Endometriosis, Fertility, Reproductive Health, Inflammation, Oxidative Stress, Stress Response

PERK (EIF2AK3) is one of three master sensors of the endoplasmic reticulum stress response. When misfolded proteins accumulate in the ER — driven by inflammatory signals, hypoxia, or oxidative damage — PERK phosphorylates eIF2α to temporarily halt protein synthesis while activating selective transcription factors...

rs7152376 Regulatory variant upstream of NFKBIA that specifically elevates risk of psoriatic arthritis over skin-only psoriasis, with a 3.2-fold odds ratio distinguishing arthritic from cutaneous-only disease in psoriasis patients

Chromosome 14 Risk Allele C Category Psoriasis & Spondyloarthropathy Tags Autoimmune, Psoriasis, Arthritis, Inflammation, Bone & Joint, Biologic Therapy

Psoriasis is not a single disease — it is a spectrum. About 2-3% of people develop psoriasis at some point in their lives, and in roughly 25-30% of them, the inflammation extends beyond the skin to attack the joints, a condition called psoriatic arthritis(https://pubmed.ncbi.nlm.nih.gov/34884808/) (PsA). Identifying...

rs725613 Intronic variant in the autophagy regulator CLEC16A that alters thymic T-cell selection and immune tolerance, influencing risk for type 1 diabetes and multiple sclerosis

Chromosome 16 Risk Allele T Category Autoimmune Tolerance & T-Cell Regulation Tags Autoimmune, Type 1 Diabetes, Multiple Sclerosis, Autophagy, T-Cell Regulation, Immune Function

Your immune system must learn to attack pathogens without attacking your own tissues — a balancing act that starts in the thymus, where T cells are educated and self-reactive cells are eliminated. CLEC16A encodes an E3 ubiquitin ligase that controls autophagy(https://pubmed.ncbi.nlm.nih.gov/25979422/) in thymic...

rs7679916 Regulatory upstream variant in the SLC2A9 promoter region; the T allele is associated with modestly elevated serum uric acid in some populations, while the C allele may confer partial protection; independent of the major coding variants at this locus and likely acts through altered GLUT9 transcriptional regulation

Chromosome 4 Risk Allele T Category Uric Acid & Kidney Function Tags Gout, Uric Acid, Kidney Function, Diet, Cardiovascular

Your kidneys filter roughly 700 mg of uric acid per day, reabsorbing most of it through transporters in the proximal tubule before it reaches the urine. The SLC2A9 gene encodes GLUT9(https://pubmed.ncbi.nlm.nih.gov/18327257/), and genetic variation across its approximately 46 kb genomic region accounts for 3–8% of...

rs80358216 Pathogenic nonsense variant introducing a premature stop codon at position 171 of 3β-hydroxysteroid dehydrogenase type II, abolishing conversion of Δ5-steroids to Δ4-steroids in adrenal glands and gonads; homozygotes develop severe salt-wasting congenital adrenal hyperplasia with deficiency of cortisol, aldosterone, and sex steroids.

Chromosome 1 Risk Allele A Category Reproductive Hormones Tags Steroid Hormones, Steroid Metabolism, Reproductive Health, Carrier Status, Congenital, Cortisol

At a single enzymatic step buried deep in the steroid hormone assembly line, 3β-hydroxysteroid dehydrogenase type II — encoded by HSD3B2 — performs one of the most consequential conversions in human biochemistry: it transforms inactive Δ5-steroids into the active Δ4-steroids that become cortisol, aldosterone,...

rs841 Intronic/3'UTR GCH1 variant tagging reduced tetrahydrobiopterin (BH4) synthesis capacity; the A allele associates with endothelial dysfunction, oxidative stress, and impaired nitric oxide production, with sex-specific effects on blood pressure

Chromosome 14 Risk Allele A Category Blood Pressure & Hypertension Tags Nitric Oxide, Endothelial Health, Cardiovascular, Hypertension, Heart Disease, Inflammation

Nitric oxide (NO) is the blood vessel's primary vasodilator — the molecule that keeps arteries relaxed, blood flowing smoothly, and blood pressure in check. GCH1 (GTP Cyclohydrolase 1)(https://pubmed.ncbi.nlm.nih.gov/24777984/) is a gatekeeper of NO production. Without adequate BH4 — the essential cofactor that...

rs9332736 Frameshift deletion in C2 exon 6 causing complete complement C2 deficiency, increasing risk of encapsulated bacterial infections and SLE; most common inherited complement deficiency in Europeans

Chromosome 6 Risk Allele D Category B-Cell Immunity & Antibody-Mediated Disease Tags Complement System, Bacterial Clearance, Vaccination, Autoimmune, Inflammation

Complement component C2(https://pubmed.ncbi.nlm.nih.gov/26941740/) sits at the intersection of innate immunity and autoimmune regulation. When an antibody-antigen complex or dying cell activates the classical complement pathway, C1q recruits C1r and C1s, which cleave C4 and then C2 into fragments that assemble the...