Research — GeneOps

rs137852912 The most severe gain-of-function PCSK9 mutation, increasing LDLR-binding affinity 10-25-fold to cause extreme LDL elevation and early-onset coronary artery disease in carriers of this rare pathogenic variant

Chromosome 1 Risk Allele T Category Atherogenic Lipoproteins Tags Cardiovascular, Cholesterol, LDL Cholesterol, Heart Disease, Atherosclerosis, Statins

PCSK9 (proprotein convertase subtilisin/kexin type 9) is a liver-secreted enzyme whose normal job is to degrade LDL receptors(https://www.ncbi.nlm.nih.gov/gene/255738) after they have been internalized. The D374Y variant strips that regulatory restraint: the mutant PCSK9 protein binds LDLR with 10-25-fold higher...

rs17175830 Intronic variant in ZFPM1 (FOG1), the master transcriptional co-regulator of megakaryopoiesis; the A allele is the strongest common GWAS signal for elevated platelet count (p=1×10⁻⁵⁰) and plateletcrit, with implications for thrombotic tendency and cardiovascular risk

Chromosome 16 Risk Allele A Category Arrhythmia & Heart Rhythm Tags Cardiovascular, Thrombosis, Blood Clotting, Heart Disease, Inflammation, Thrombophilia

Every platelet in your blood begins its life inside a megakaryocyte, a giant bone-marrow cell that releases thousands of platelets by extending cytoplasmic protrusions into blood vessels. How many megakaryocytes your bone marrow produces — and how efficiently each one generates platelets — is tightly controlled by a...

rs17878486 Intronic variant in amelogenin X-linked gene affecting enamel mineralization and susceptibility to dental caries and developmental enamel defects

Chromosome X Risk Allele T Category Dental & Oral Health Tags Dental & Oral Health, Enamel Health, Bone Health, Minerals, Calcium

Tooth enamel is the hardest tissue in the human body, yet it is built entirely before birth and in early childhood — once formed, it cannot be regenerated. The blueprint for enamel quality is written largely in the AMELX gene, which encodes amelogenin(https://pubmed.ncbi.nlm.nih.gov/19079557/). This intronic variant...

rs1799782 Missense variant in the linker region of XRCC1 that disrupts interaction with the OGG1 glycosylase, impairing base excision repair of oxidative DNA damage; effect direction varies by cancer type and ancestry

Chromosome 19 Risk Allele A Category Cancer Risk Tags Cancer Risk, DNA Repair, Base Excision Repair, Smoking Interaction, Ancestry

XRCC1 (X-Ray Repair Cross-Complementing group 1) is the master scaffold protein of base excision repair (BER)(https://www.ncbi.nlm.nih.gov/gene/7515). Rather than cutting or unwinding DNA itself, XRCC1 acts as a molecular coordinator — physically recruiting and organizing the enzymes that detect, excise, and patch...

rs1019385 Promoter variant in the GRIN2B Sp1 binding site that reduces NR2B subunit expression, lowering NMDA receptor activity critical for learning and memory

Chromosome 12 Risk Allele A Category Neurology & Cognition Tags Cognition, Memory, Neuroplasticity, Neurotransmitters, Neurological Risk, Brain Health

Your brain's ability to learn and form lasting memories depends on NMDA receptors(https://pubmed.ncbi.nlm.nih.gov/25467983/). The NR2B subunit, encoded by GRIN2B, is the dominant regulatory subunit in the adult cortex and hippocampus — its expression level directly controls how strongly synapses can potentiate in...

rs1044498 ENPP1 K121Q variant that increases ENPP1 binding affinity to the insulin receptor by 2–3 fold, blunting insulin signaling and raising insulin resistance risk.

Chromosome 6 Risk Allele C Category Blood Sugar & Diabetes Tags Insulin Resistance, Diabetes, Metabolic Health, Obesity, Cardiovascular, Energy Metabolism

Your cells are constantly reading signals from insulin, but a protein called ENPP1 acts as a natural brake on that process. The K121Q variant of ENPP1 is one of the best-studied functional polymorphisms in metabolic genetics — and it makes that brake more powerful than it should be. Carriers of the Q allele have an...

rs1045642 Synonymous variant in P-glycoprotein affecting drug efflux pump expression and hundreds of substrate drugs

Chromosome 7 Risk Allele A Category Pharmacogenomics Tags Drug Metabolism, Pharmacogenomics, Immunosuppressants, Cardiovascular, Chemotherapy

P-glycoprotein is your body's master bouncer, stationed at critical barriers — the gut, liver, kidneys, blood-brain barrier — pumping hundreds of drugs and toxins back out before they can accumulate. The ABCB1 gene(https://www.ncbi.nlm.nih.gov/gene/5243) on chromosome 7 creates this ATP-dependent efflux transporter,...

rs104894138 Pathogenic missense variant abolishing 17α-hydroxylase/17,20-lyase activity, causing combined cortisol and sex steroid deficiency with mineralocorticoid excess

Chromosome 10 Risk Allele A Category Reproductive Hormones Tags Steroid Hormones, Fertility, Hormones, Genetic Counseling, Reproductive Health, Hypertension

CYP17A1 encodes cytochrome P450 17α-hydroxylase/17,20-lyase, an enzyme that sits at a critical junction in human steroid biosynthesis. It performs two consecutive chemical reactions: first converting pregnenolone to 17α-hydroxypregnenolone (the 17-hydroxylase step), then cleaving that intermediate to yield DHEA and...

rs1048943 Phase I detoxification enzyme that activates polycyclic aromatic hydrocarbons and metabolizes estrogens; the Val variant increases catalytic activity, producing more reactive intermediates

Chromosome 15 Risk Allele C Category Methylation & Detox Tags Detoxification, Phase I, Xenobiotics, Cardiovascular, Diet

Cytochrome P450 1A1 (CYP1A1) is a Phase I detoxification enzyme() with a dual role that makes it both protector and potential threat. On one hand, CYP1A1 initiates the breakdown of polycyclic aromatic hydrocarbons (PAHs)(), dioxins, and other environmental pollutants. On the other hand, the intermediates it creates...

rs104894654 Missense variant in alpha-dystrobrevin disrupting the EF-hand calcium-binding domain, associated with left ventricular noncompaction cardiomyopathy in a single Japanese family

Chromosome 18 Risk Allele T Category Cardiomyopathy & Structural Heart Tags Cardiovascular, Heart Disease, Congenital, Biomarkers, Genetic Counseling

Alpha-dystrobrevin (encoded by DTNA) is a structural adaptor protein that anchors the dystrophin-glycoprotein complex (DGC)(https://pubmed.ncbi.nlm.nih.gov/11238270/) to the inner surface of the cardiac muscle cell membrane. It acts as a molecular linchpin, physically coupling dystrophin to syntrophins and other...