Research — GeneOps

rs121434290 Pathogenic missense variant in the ZIP4 intestinal zinc transporter; homozygosity causes acrodermatitis enteropathica, a rare but fully treatable zinc malabsorption disorder

Chromosome 8 Risk Allele T Category Iron & Mineral Transport Tags Zinc, Minerals, Micronutrients, Carrier Status, Genetic Counseling, Gut Health

Your body cannot make zinc — every atom of it must come through your intestine. ZIP4(), the protein encoded by SLC39A4, sits at the brush border of the small intestine and acts as the primary gateway for dietary zinc absorption. When both copies of SLC39A4 carry loss-of-function variants, zinc simply cannot get in —...

rs1217414 Intronic PTPN22 variant independently associated with psoriasis and ankylosing spondylitis, operating through a distinct mechanism from the established R620W risk allele

Chromosome 1 Risk Allele A Category Autoimmune Tolerance & T-Cell Regulation Tags Autoimmune, Immune System, Psoriasis, T-Cell Regulation, Arthritis, Immune & Autoimmune

The PTPN22 gene is widely known for its R620W variant (rs2476601), one of the strongest non-HLA autoimmune risk factors. But R620W is not the only functional player in this locus. Deep sequencing and haplotype studies have revealed that multiple independent signals exist within...

rs121909569 Likely pathogenic missense variant in antithrombin III; the G allele converts Ser148 to Pro, causing type II pleiotropic antithrombin deficiency that reduces both anticoagulant activity and antigen levels, substantially elevating lifetime VTE risk in heterozygous carriers

Chromosome 1 Risk Allele G Category Von Willebrand & Anticoagulant Proteins Tags Blood Clotting, Thrombophilia, Cardiovascular, Blood Thinners, Genetic Counseling, Women's Health

Antithrombin — encoded by SERPINC1 on chromosome 1 — is the principal brake on coagulation. It is a serpin(https://pubmed.ncbi.nlm.nih.gov/19404531/) that permanently inactivates thrombin and Factor Xa, the two enzymes most responsible for generating fibrin clot. Without functional antithrombin, coagulation runs...

rs121917746 Nonsense variant in sepiapterin reductase that abolishes BH4 biosynthesis, causing dopamine and serotonin deficiency in the brain; homozygosity leads to DOPA-responsive dystonia (SPR deficiency, OMIM

Chromosome 2 Risk Allele T Category Vitamins & Nutrient Absorption Tags Neurotransmitters, Dopamine, Serotonin, Carrier Status, Neurological Risk, Micronutrients

Inside every neuron that makes dopamine or serotonin, a small enzyme called sepiapterin reductase (SPR) performs the final step in synthesising tetrahydrobiopterin(https://pubmed.ncbi.nlm.nih.gov/33903016/). Without sufficient BH4, the enzymes that convert tyrosine into dopamine and tryptophan into serotonin grind...

rs12191877 Tag SNP for HLA-C*06:02, the strongest genetic risk factor for psoriasis, determining disease phenotype and predicting differential response to biologic therapy

Chromosome 6 Risk Allele T Category Psoriasis & Spondyloarthropathy Tags Immune & Autoimmune, Psoriasis, Autoimmunity, HLA, Skin, Biologic Therapy, Autoimmune, Skin Health, Immune & Gut

HLA-C(https://www.ncbi.nlm.nih.gov/gene/3107) sits at the heart of the psoriasis story. The rs12191877 SNP is a tag variant(https://pubmed.ncbi.nlm.nih.gov/19680446/) for the HLA-C06:02 allele (historically called HLA-Cw6), the most strongly replicated genetic risk factor for psoriasis ever identified. Unusually for...

rs12350739 Intergenic enhancer variant controlling BNC2 expression in melanocytes; determines pigmentation saturation and freckling tendency with implications for UV sensitivity and skin cancer risk

Chromosome 9 Risk Allele A Category Skin & Eyes Tags Skin Pigmentation, Freckling, UV Sensitivity, Skin Cancer, Cancer Risk, Sun Sensitivity

BNC2 encodes basonuclin-2, a zinc finger transcription factor(https://pubmed.ncbi.nlm.nih.gov/19956727/) that is expressed in melanocytes and plays an essential role in supporting the survival and patterning of pigment-producing cells. Unlike the better-known pigmentation genes (MC1R, TYR, OCA2) that act directly...

rs1260326 Coding GCKR variant (Pro446Leu) that directly reduces GCKRP sensitivity to fructose-6-phosphate, constitutively activating hepatic glucokinase and producing the characteristic trade-off of lower fasting glucose and insulin resistance against higher triglycerides, CRP, and NAFLD risk

Chromosome 2 Risk Allele T Category Liver Fat Tags Triglycerides, Fat Metabolism, Insulin, Cardiovascular, Diet, Liver Health

Glucokinase regulatory protein (GCKRP), encoded by the GCKR gene on chromosome 2, acts as the master brake on hepatic glucokinase (GCK), the enzyme responsible for the liver's glucose uptake after a meal. The rs1260326 Pro446Leu variant(https://pubmed.ncbi.nlm.nih.gov/18678614/) is the functional coding variant that...

rs12678919 Intergenic variant 19 kb downstream of lipoprotein lipase (LPL) that tags a regulatory region affecting LPL expression; the rare G allele is associated with meaningfully lower triglycerides and higher HDL cholesterol.

Chromosome 8 Risk Allele A Category Triglycerides & Fatty Acids Tags Triglycerides, HDL Cholesterol, Fat Metabolism, Cardiovascular, Lipid Metabolism

Lipoprotein lipase (LPL()) is the central enzyme in plasma triglyceride clearance. The variant rs12678919 sits in a regulatory region roughly 19 kilobases downstream of the LPL gene body. It is an intergenic tag SNP that marks a haplotype block associated with altered LPL expression or activity — the precise...

rs13412535 Intronic regulatory variant in SERPINE2 that modulates expression of Protease Nexin-1, the most potent tissue thrombin inhibitor, shifting fibrinolytic balance and elevating venous thromboembolism risk

Chromosome 2 Risk Allele A Category Coagulation & Clotting Factors Tags Thrombosis, Blood Clotting, Fibrinolysis, Cardiovascular, Heart Disease, Thrombophilia

Most genetic thrombophilia testing focuses on the coagulation cascade: Factor V Leiden, prothrombin G20210A, antithrombin deficiency. These variants are clinically established but together account for fewer than half of all heritable VTE cases. rs13412535, a regulatory variant in the SERPINE2 gene, points to a...

rs137853964 LDLR missense variant at position 827 within the cytoplasmic NPXY internalization motif; classified as uncertain significance for familial hypercholesterolemia, with conflicting functional and population evidence — the more common G>A change (Val827Ile) shows no LDL uptake impairment in functional assays, while the rarer G>T change (Val827Phe) has been reported in FH patients

Chromosome 19 Risk Allele A Category Atherogenic Lipoproteins Tags Cholesterol, LDL Cholesterol, Cardiovascular, Genetic Counseling, Heart Disease, Lipid Metabolism

The LDLR gene is the master regulator of LDL cholesterol clearance from the bloodstream. The LDLR protein captures LDL particles circulating in blood and shuttles them into liver cells for degradation, keeping circulating LDL-C in check. When LDLR function is reduced or absent — as in classical FH — LDL-C...