Research — GeneOps

rs201065226 Rare stop-gain variant in CPT2 abolishing carnitine palmitoyltransferase II, the enzyme that shuttles long-chain fatty acids into mitochondria; carriers face elevated risk of exercise-induced rhabdomyolysis

Chromosome 1 Risk Allele T Category Metabolic Enzymes & Rare Disorders Tags Fat Metabolism, Mitochondria, Exercise, Muscle, Carrier Status, Energy Metabolism

The human body runs on fat during sustained exercise and fasting — but getting fatty acids into mitochondria requires a molecular ferry service. CPT2 (carnitine palmitoyltransferase II) is the enzyme that completes this ferry crossing, releasing long-chain acyl groups into the mitochondrial matrix for...

rs201457110 Rare pathogenic missense variant in DCHS1 (R2513H) causing mitral valve prolapse type 2 through loss of protein stability and disrupted planar cell polarity signaling during valve development

Chromosome 11 Risk Allele T Category Cardiomyopathy & Structural Heart Tags Cardiovascular, Heart Disease, Connective Tissue, Arrhythmia, Genetic Counseling

Mitral valve prolapse (MVP) affects approximately 1 in 40 people globally, making it the most common heart valve abnormality — yet for decades its molecular causes were largely unknown. DCHS1 (Dachsous Cadherin-Related 1) encodes a protocadherin that functions as an intercellular signal in the planar cell polarity...

rs2075570 MTX1 intronic variant at 1q22 tagging a gastric cancer susceptibility locus that regulates mucosal integrity via the MUC1/UBAP2L axis

Chromosome 1 Risk Allele T Category IBD & Mucosal Immunity Tags Gastric Health, H. pylori, Digestive Health, Cancer Risk, Gut Microbiome

Chromosome 1q22 is one of the most consistently replicated gastric cancer susceptibility regions in the human genome. rs2075570 is an intronic variant(https://www.ncbi.nlm.nih.gov/snp/rs2075570) that serves as a tag SNP for this locus — a marker in tight linkage...

rs2241766 Synonymous exon 2 variant in the adiponectin gene that affects mRNA stability and adiponectin secretion; the G allele is associated with lower circulating adiponectin, higher metabolic syndrome risk, and altered fat distribution

Chromosome 3 Risk Allele G Category Coronary Artery Disease & Atherosclerosis Tags Fat Metabolism, Obesity, Insulin, Inflammation, Cardiovascular, Diet

Adiponectin is the most abundant hormone secreted by fat cells, and despite being produced in adipose tissue it works against the pathological consequences of excess fat: it sensitizes muscle and liver to insulin, suppresses the inflammatory cytokines that drive adipose tissue fibrosis, and inhibits the TGF-β...

rs2271933 Missense variant in the orexin/hypocretin receptor 1 that alters G-protein signaling, increasing susceptibility to migraine, panic disorder, mood dysregulation, and heightened arousal responses

Chromosome 1 Risk Allele A Category Mood & Behavior Tags Migraine, Mood, Anxiety, Sleep, Brain Health

The orexin system() is one of the brain's master regulators, orchestrating the balance between wakefulness and sleep, appetite and satiety, arousal and calm. The HCRTR1 gene encodes the orexin receptor 1 (OX1R)(), the primary target for orexin-A signaling. The rs2271933 variant causes an isoleucine-to-valine...

rs2476601 The strongest non-HLA autoimmune risk allele, affecting T-cell and B-cell signaling threshold

Chromosome 1 Risk Allele A Category Autoimmune Tolerance & T-Cell Regulation Tags Autoimmune, Immune System, Rheumatoid Arthritis, Type 1 Diabetes, Lupus, Vitiligo

The PTPN22 gene encodes lymphoid tyrosine phosphatase (LYP), a critical brake on T-cell and B-cell activation. This enzyme acts as a master regulator of immune signaling, dephosphorylating key proteins(https://pubmed.ncbi.nlm.nih.gov/36961507/) in the T-cell receptor pathway to prevent overactivation. The R620W...

rs2501431 Synonymous coding variant in the cannabinoid receptor 2 gene that tags a haplotype block influencing CB2 receptor expression in immune cells; the G allele (coding-strand C) is associated with elevated rheumatoid arthritis risk and altered endocannabinoid-mediated immune regulation

Chromosome 1 Risk Allele G Category TNF, NF-kB & Inflammatory Cytokines Tags Endocannabinoid, Autoimmune, Inflammation, Rheumatoid Arthritis, Immune Function, Arthritis

The endocannabinoid system is best known for its role in the brain, but cannabinoid receptor 2 (CB2)(https://pubmed.ncbi.nlm.nih.gov/34099105/) rather than in the central nervous system. CB2 is a key gatekeeper of immune activity: when activated by endogenous ligands (2-AG, AEA) or exogenous cannabinoids, it...

rs2867125 Regulatory variant at the TMEM18 locus on chromosome 2p25.3 — one of the most replicated obesity GWAS signals — modulating hypothalamic appetite suppression via the paraventricular nucleus

Chromosome 2 Risk Allele C Category Appetite & Obesity Tags Obesity, Appetite, Fat Metabolism, Diabetes, Energy Metabolism

The chromosome 2p25.3 region, home to TMEM18 (Transmembrane Protein 18), harbors one of the most robustly replicated obesity loci in human genetics. rs2867125 is a regulatory variant that sits within this locus, influencing how the brain's central appetite-regulation hub — the hypothalamic paraventricular nucleus...

rs28941784 Missense variant eliminating MMAB adenosylcobalamin synthase activity; the most common pathogenic allele in European cblB methylmalonic acidemia, causing absent enzyme protein and complete block of adenosylcobalamin synthesis

Chromosome 12 Risk Allele A Category Vitamins & Nutrient Absorption Tags Vitamin B12, B Vitamins, Metabolic, Carrier Status, Reproductive Health, Micronutrients

Vitamin B12 that arrives in your mitochondria is not yet useful. Before it can power the critical enzyme methylmalonyl-CoA mutase (MCM)(https://pubmed.ncbi.nlm.nih.gov/22661206/), the vitamin must be converted to its active mitochondrial cofactor form — adenosylcobalamin (AdoCbl). That final conversion step is...

rs3129878 Intronic variant in the HLA class II region associated with nonobstructive azoospermia risk, likely through immune-mediated disruption of testicular spermatogenesis

Chromosome 6 Risk Allele C Category Endometriosis & Uterine Health Tags Male Fertility, HLA, Autoimmune, Fertility, Sperm Quality, Reproductive Health

The human leukocyte antigen (HLA) region(https://www.ncbi.nlm.nih.gov/gene/3122/) on chromosome 6 is the master regulator of adaptive immunity — and rs3129878, an intronic variant in HLA-DRA, sits within one of its most functionally dense segments. HLA-DRA encodes the alpha chain of the HLA-DR heterodimer, the class...