Research — GeneOps

rs28936415 The most common pathogenic PMM2 variant, causing phosphomannomutase 2 deficiency and PMM2-CDG (congenital disorder of glycosylation type Ia) when inherited in compound heterozygous form; homozygous R141H is embryonic lethal

Chromosome 16 Risk Allele A Category Metabolic Enzymes & Rare Disorders Tags Congenital, Carrier Status, Genetic Counseling, Micronutrients, Metabolic, Neurological Risk

Every protein destined for export, membrane display, or passage through the secretory pathway must be decorated with sugar chains — a process called N-linked glycosylation(). This process depends on a supply of activated sugar building blocks, and the enzyme phosphomannomutase 2 (PMM2) is the gatekeeper for one of...

rs28942084 Pathogenic LDLR missense variant in the EGF precursor domain causing familial hypercholesterolemia with severely elevated LDL-C and early cardiovascular disease

Chromosome 19 Risk Allele T Category Cholesterol & Lipoproteins Tags Cholesterol, Cardiovascular, Fat Metabolism, Statins, LDL Cholesterol

The LDL receptor (LDLR) is the liver's primary mechanism for clearing low-density lipoprotein() from the bloodstream. Each hepatocyte displays roughly 50,000 LDL receptors that continuously cycle between the cell surface and endosomes, capturing LDL particles and internalizing them for degradation. When LDLR...

rs35936514 Intronic/3'UTR variant in LHPP, a histidine phosphatase essential for stress resilience in the prefrontal cortex — the T allele is associated with increased risk for major depressive disorder, particularly following chronic stress

Chromosome 10 Risk Allele T Category Mood & Behavior Tags Depression, Stress Response, Neuroplasticity, Mental Health, Mood, Brain Health

Most people associate depression with serotonin. LHPP tells a different story — one about a small enzyme in the prefrontal cortex that quietly prevents stress from reshaping your brain. When LHPP function is reduced, chronic stress finds an open door into the neural circuitry that governs mood, motivation, and...

rs3850641 Intronic variant in TNFSF4 (OX40 ligand) linked to a promoter haplotype that reduces OX40L expression; homozygous G carriers show approximately 2-fold increased myocardial infarction risk in some populations, with the strongest signal in women

Chromosome 1 Risk Allele G Category Coronary Artery Disease & Atherosclerosis Tags Cardiovascular, Atherosclerosis, Autoimmunity, T-Cell Regulation, Inflammation

TNFSF4 encodes OX40 ligand (OX40L, also called CD252), a co-stimulatory molecule of the TNF superfamily that serves as the key amplifier of T-cell activation in inflammatory settings. OX40L is expressed on antigen-presenting cells — particularly macrophages, dendritic cells, and vascular endothelial cells — and...

rs3890745 Intronic variant near MMEL1 and TNFRSF14 on chromosome 1p36; the C allele is associated with increased susceptibility to rheumatoid arthritis and other autoimmune conditions through disrupted immune costimulatory signaling at the HVEM/LIGHT/BTLA axis

Chromosome 1 Risk Allele C Category TNF, NF-kB & Inflammatory Cytokines Tags Rheumatoid Arthritis, Autoimmune, Immune & Autoimmune, T-Cell Regulation, B-Cell Signaling, Inflammation

On the short arm of chromosome 1, at position 1p36, two genes sit in close proximity with distinct but complementary roles in immune homeostasis: MMEL1, encoding a neprilysin-like metalloendopeptidase, and TNFRSF14, encoding HVEM(https://www.ncbi.nlm.nih.gov/gene/8764). The rs3890745 intronic...

rs396991 Missense variant in Fc gamma receptor IIIa (CD16a) that determines NK cell IgG binding affinity and antibody-dependent cellular cytotoxicity — major pharmacogenomic factor for monoclonal antibody therapy response

Chromosome 1 Risk Allele C Category Innate Immunity & Infection Defense Tags Immune & Gut, Pharmacogenomics, Innate Immunity, Autoimmune, Cancer Treatment, Drug Response

Your body's natural killer (NK) cells carry a surface receptor called FcgammaRIIIa (CD16a)(https://www.ncbi.nlm.nih.gov/gene/2214) that connects innate immunity to antibody-mediated defense. This receptor grabs the tail end of IgG antibodies already bound to target cells — infected cells, cancer cells, or cells...

rs397507173 Rare missense variant in the biotinidase enzyme (p.Pro167Ser); a likely pathogenic allele for biotinidase deficiency. Heterozygous carriers have reduced but usually sufficient biotinidase activity; compound heterozygosity with other BTD pathogenic variants can cause partial or profound deficiency requiring lifelong biotin supplementation.

Chromosome 3 Risk Allele T Category Vitamins & Nutrient Absorption Tags B Vitamins, Micronutrients, Carrier Status, Metabolic, Neurological Risk, Vitamins

Biotin (vitamin B7) is indispensable for four carboxylase enzymes() that power fat synthesis, amino acid metabolism, and gluconeogenesis. Unlike most vitamins, biotin is largely recovered from food proteins rather than absorbed free — the digestive breakdown of biotin-dependent enzymes in the diet releases...

rs397514752 Ultra-rare autosomal recessive MYBPC3 missense variant; homozygotes develop severe HCM while heterozygous carriers remain clinically unaffected up to age 71 in the single reported family

Chromosome 11 Risk Allele A Category Cardiomyopathy & Structural Heart Tags Cardiovascular, Heart Disease, Genetic Counseling, Carrier Status, Congenital

Cardiac myosin-binding protein C (cMyBP-C), encoded by MYBPC3 on chromosome 11, is a thick-filament accessory protein that accounts for roughly 2% of myofibrillar protein mass(https://pubmed.ncbi.nlm.nih.gov/23396983/). Its C-terminal domains anchor it to the thick filament while its N-terminal domains regulate...

rs4072037 Mucin-1 gene variant affecting gastric mucus barrier function and H. pylori colonization resistance

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

The MUC1 gene encodes mucin-1, a membrane-bound glycoprotein(https://pubmed.ncbi.nlm.nih.gov/25332893/) that plays a crucial role in protecting the gastric lining from environmental insults, particularly the bacterium Helicobacter pylori (H. pylori)(https://pubmed.ncbi.nlm.nih.gov/38463926/). The rs4072037 variant,...

rs509035 Intronic variant in the ghrelin receptor gene; the A allele is associated with higher fat-free mass, greater stature, and elevated serum IGF-1, reflecting enhanced GHSR-driven growth hormone pulsatility and its downstream anabolic effects on body composition

Chromosome 3 Risk Allele A Category Appetite & Obesity Tags Appetite, Obesity, Metabolic Health, Hormones, Fat Metabolism, Insulin

Ghrelin does far more than signal hunger. When it docks onto GHSR-1a (growth hormone secretagogue receptor)(https://pubmed.ncbi.nlm.nih.gov/28134808/), it triggers a powerful pulse of growth hormone release from the pituitary. That GH pulse drives the liver to secrete IGF-1 (insulin-like growth factor...