Research — GeneOps

rs2672598 Promoter variant at -487 in HTRA1 that elevates HTRA1 serine protease expression, disrupting TGF-β signaling and extracellular matrix remodeling in the retina and increasing risk of neovascular (wet) age-related macular degeneration

Chromosome 10 Risk Allele C Category Longevity & Aging Tags Longevity, Aging, Eye Health, Retinal Health, Inflammation, Angiogenesis

The 10q26 chromosomal locus is the second strongest genetic risk factor for age-related macular degeneration (AMD), second only to the complement factor H (CFH) gene on chromosome 1. Within the 10q26 locus sit two genes in strong linkage disequilibrium: ARMS2 (also called LOC387715) and HTRA1. rs2672598 is a...

rs28936701 Pathogenic CYP1B1 missense variant (Arg469Trp) that severely reduces enzyme activity and is a leading genetic cause of primary congenital glaucoma, particularly in Middle Eastern, Iranian, and Pakistani populations

Chromosome 2 Risk Allele A Category Vascular Inflammation & Remodeling Tags Glaucoma, Eye Health, Vision, Steroid Metabolism, Cardiovascular, Cancer Risk

The CYP1B1 gene encodes cytochrome P450 1B1(https://www.ncbi.nlm.nih.gov/gene/1545). It is expressed broadly but is especially important in anterior eye segment tissues during fetal development. The Arg469Trp substitution at rs28936701 is one of the most clinically significant missense variants in CYP1B1 — a...

rs374304304 Pathogenic missense variant in argininosuccinate lyase that reduces urea cycle enzyme activity to ~12% of normal, causing argininosuccinic aciduria when inherited in biallelic form; heterozygous carriers are typically asymptomatic but carry the allele at reproductive risk

Chromosome 7 Risk Allele T Category Metabolic Enzymes & Rare Disorders Tags Carrier Status, Congenital, Genetic Counseling, Nitric Oxide, Blood Pressure, Liver Health

Every gram of protein you eat generates ammonia as a byproduct of amino acid catabolism. Left unchecked, ammonia is neurotoxic — even modest elevations cause brain swelling, seizures, and coma. The urea cycle exists specifically to neutralize this threat, converting ammonia into urea for renal excretion across five...

rs3846663 Intronic HMGCR variant that tags a haplotype influencing exon 13 alternative splicing — affecting HMGCR enzyme activity, baseline LDL-C levels, and the magnitude of statin-induced LDL reduction

Chromosome 5 Risk Allele T Category Cholesterol & Lipoproteins Tags Cholesterol, LDL Cholesterol, Statins, Fat Metabolism, Cardiovascular, Pharmacogenomics

Every statin ever prescribed targets one protein: HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the cholesterol biosynthesis pathway. What most people don't know is that the HMGCR gene produces two versions of its own enzyme — a full-length, fully active form and a shorter variant missing 53 amino acids...

rs397516394 Ultra-rare TPM1 missense variant of uncertain significance found in hypertrophic cardiomyopathy panels; alters a residue where other pathogenic substitutions are known, but evidence is insufficient for definitive pathogenicity classification

Chromosome 15 Risk Allele G Category Cardiomyopathy & Structural Heart Tags Cardiovascular, Heart Disease, Arrhythmia, Genetic Counseling, Carrier Status

When a genetic test returns a "variant of uncertain significance" (VUS) in a cardiomyopathy gene, it sits in one of medicine's most difficult grey zones: clinically actionable enough to flag, not conclusive enough to act on alone. rs397516394 — a missense substitution that converts methionine to valine at position...

rs398123138 Pathogenic 5-bp frameshift deletion in the biotinidase enzyme gene, eliminating the final 41 amino acids of the protein and causing biotinidase deficiency when inherited in biallelic form; heterozygotes are asymptomatic carriers

Chromosome 3 Risk Allele D Category Vitamins & Nutrient Absorption Tags B Vitamins, Micronutrients, Carrier Status, Vitamins, Genetic Counseling, Metabolic

Biotinidase(https://pubmed.ncbi.nlm.nih.gov/20301497/) is the enzyme responsible for regenerating free biotin from protein-bound forms in the diet and from normal cellular protein turnover. Without it, the body cannot recycle its biotin supply — a cofactor that four essential carboxylase enzymes depend on for amino...

rs4252185 Intronic PLG variant (intron 1) whose C allele is enriched in Europeans and appears in cardiovascular GWAS signals at the PLG/LPA locus; PLG encodes plasminogen, the serine-protease zymogen central to fibrinolysis, macrophage recruitment, and innate mucosal immunity

Chromosome 6 Risk Allele C Category Innate Immunity & Infection Defense Tags Innate Immunity, Fibrinolysis, Cardiovascular, Infection Risk, Inflammation

Plasminogen is one of the body's most versatile proteases-in-waiting. Synthesised primarily in the liver, it circulates as an inactive zymogen until activated by tissue plasminogen activator (tPA) or urokinase (uPA)(https://pubmed.ncbi.nlm.nih.gov/25208887/) to form plasmin — the active enzyme that dissolves fibrin...

rs4570625 Promoter variant affecting brain serotonin synthesis enzyme; influences emotional reactivity, anxiety, and depression risk

Chromosome 12 Risk Allele G Category Mood & Behavior Tags Mental Health, Neurotransmitters, Depression, Anxiety, Stress Response, Serotonin

TPH2 (tryptophan hydroxylase 2) is the rate-limiting enzyme(https://pubmed.ncbi.nlm.nih.gov/16192985/) for serotonin synthesis in the brain. Unlike its cousin TPH1, which makes serotonin in the gut and other peripheral tissues, TPH2 works exclusively in neurons—particularly in the raphe...

rs4888378 Intronic CFDP1 locus variant that regulates BCAR1 expression in vascular tissue via FOXA binding; the A allele reduces BCAR1 levels and is associated with lower carotid intima-media thickness progression and reduced coronary artery disease risk, with the protective effect strongest in women

Chromosome 16 Risk Allele G Category Coronary Artery Disease & Atherosclerosis Tags Atherosclerosis, Cardiovascular, Heart Disease, Endothelial Health, Inflammation

The rs4888378 variant sits within an intron of CFDP1 (Craniofacial Development Protein 1) on chromosome 16q23, but the functionally relevant gene it controls is a neighbor: BCAR1 (Breast Cancer Anti-Estrogen Resistance 1(https://pubmed.ncbi.nlm.nih.gov/23152477/)). GWAS analysis identified this locus as one of 64...

rs492602 A synonymous FUT2 proxy variant in strong LD with the W143X nonsense allele (rs601338), tagging secretor status and associated with Crohn's disease susceptibility, psoriasis risk, and gut microbiome composition; the G allele marks the secretor phenotype

Chromosome 19 Risk Allele A Category IBD & Mucosal Immunity Tags Secretor Status, Gut Microbiome, Autoimmune, Crohn's Disease, Psoriasis, IBD

Your FUT2 gene is the master switch for secretor status(). rs492602 is a synonymous proxy variant that tags this biological divide: the G allele travels with the secretor phenotype, while the A allele travels with the non-secretor phenotype that arises from the nearby W143X nonsense mutation() (rs601338). Although...