Research — GeneOps

rs1799889 Promoter insertion/deletion polymorphism that controls PAI-1 (plasminogen activator inhibitor-1) expression; the 4G allele (G on the plus strand) raises PAI-1 levels, suppresses fibrinolysis, and increases risk of venous thromboembolism, myocardial infarction, preeclampsia, and recurrent pregnancy loss

Chromosome 7 Risk Allele G Category Coagulation & Clotting Factors Tags Fibrinolysis, Thrombosis, Blood Clotting, Cardiovascular, Thrombophilia, Heart Disease

The body dissolves blood clots through a process called fibrinolysis, which depends on tissue plasminogen activator (tPA) converting plasminogen into plasmin — the enzyme that breaks down fibrin clots. Plasminogen activator inhibitor-1 (PAI-1), encoded by the SERPINE1 gene, is the primary brake on this system. When...

rs1799950 Common missense variant near the BRCA1 RING finger domain; associated with modestly elevated breast cancer risk (OR ~1.1-1.3) but classified as benign/likely benign — not a pathogenic BRCA1 mutation

Chromosome 17 Risk Allele C Category Cancer Risk Tags Cancer Risk, BRCA, DNA Repair, Cancer Screening, Breast Cancer

BRCA1 is perhaps the most recognized cancer-associated gene in public awareness, largely because rare, high-penetrance pathogenic mutations() in BRCA1 confer lifetime breast cancer risks of 60-80%. The rs1799950 variant (Q356R) is fundamentally different: it is a common missense polymorphism found in roughly 5% of...

rs1799977 Missense variant in the MLH1 ATPase domain (c.655A>G, p.Ile219Val) that substitutes isoleucine for valine at a conserved hydrophobic position; classified benign for Lynch syndrome with intact mismatch repair activity, but the G allele shows modest associations with altered DNA repair kinetics and may influence meiotic recombination efficiency

Chromosome 3 Risk Allele G Category Gamete Quality & DNA Repair Tags DNA Repair, Mismatch Repair, Genomic Stability, Cancer Risk, Fertility, Sperm Quality

MLH1 (mutL homolog 1) is a cornerstone of the DNA mismatch repair (MMR) system(https://pubmed.ncbi.nlm.nih.gov/8673133/), the cellular proofreading machinery that catches errors after DNA replication. MLH1 heterodimerizes with PMS2 to form MutLα, which acts as the "decision-maker" complex that couples mismatch...

rs1993116 Intronic regulatory variant in CYP2R1 that reduces hepatic vitamin D 25-hydroxylase expression, lowering the rate of vitamin D activation and increasing susceptibility to vitamin D insufficiency

Chromosome 11 Risk Allele G Category Vitamin D Metabolism Tags Vitamin D, Vitamins, Bone Health, Cardiovascular, Diet

The CYP2R1 gene(https://www.ncbi.nlm.nih.gov/gene/120227) is the gatekeeper of vitamin D activation. Before vitamin D can do anything useful in the body, the liver must convert it from its ingested or sun-derived form into 25-hydroxyvitamin D (25(OH)D)(https://pubmed.ncbi.nlm.nih.gov/25085266/). CYP2R1 performs this...

rs199473521 Ultra-rare KCNH2 missense variant substituting asparagine for lysine at position 595 in the C-linker domain, associated with congenital long QT syndrome type 2 through impaired hERG channel function

Chromosome 7 Risk Allele A Category Arrhythmia & Heart Rhythm Tags Arrhythmia, Cardiovascular, Heart Disease, Genetic Counseling, Pharmacogenomics

Every normal heartbeat ends the same way: a wave of potassium ions flows out through millions of hERG channels, repolarizing ventricular muscle and resetting the electrical system for the next beat. The hERG channel(https://pubmed.ncbi.nlm.nih.gov/19926013/) is so critical to this process that loss-of-function...

rs2235091 Intronic variant in kallikrein-4 that encodes the enamel maturation protease; A allele associated with increased caries susceptibility and molar hypomineralization in permanent dentition

Chromosome 19 Risk Allele A Category Dental & Oral Health Tags Dental & Oral Health, Enamel Health, Minerals, Calcium, Bone Health

Most people think of tooth enamel as something that forms passively in the womb and during early childhood. What is less well known is that forming enamel passes through two fundamentally different phases — and the second phase, maturation, is where the bulk of mineral is deposited and where enamel either becomes...

rs10456100 Intronic variant near KCNK5 that reduces TASK2 potassium channel expression and increases migraine susceptibility; the T allele is associated with lower KCNK5 expression and an ~5% elevated odds of migraine per allele in the largest GWAS to date.

Chromosome 6 Risk Allele T Category Neurology & Cognition Tags Migraine, Neurological Risk, Pain Sensitivity, Brain Health, Chronic Pain, Neuroinflammation

Hidden in an intron of the KCNK5 gene is a common variant that nudges the brain slightly closer to migraine. KCNK5 encodes TASK2 (https://pubmed.ncbi.nlm.nih.gov/12580339/). Unlike voltage-gated potassium channels that open and close in milliseconds, TASK2 operates as a constitutive "leak" channel — always slightly...

rs104894007 Pathogenic glucokinase missense variant that nearly abolishes enzyme activity (Kcat/S0.5 ratio 0.0001 vs wild-type), causing autosomal dominant maturity-onset diabetes of the young type 2 (MODY2) in heterozygous carriers — lifelong mild stable fasting hyperglycemia that does not require pharmacological treatment

Chromosome 7 Risk Allele A Category Blood Sugar & Diabetes Tags Diabetes, MODY, Pancreatic Beta Cell, Fasting Glucose, Carrier Status, Genetic Counseling

Every time you eat, your pancreatic beta cells monitor rising blood glucose and release insulin in proportion. The enzyme at the heart of this monitoring system is glucokinase — the molecular glucose sensor. In people who carry the Thr228Met variant, this sensor is nearly non-functional on one allele: the Kcat/S0.5...

rs104894142 Pathogenic CYP17A1 missense variant causing combined 17α-hydroxylase/17,20-lyase deficiency; homozygotes lose all sex steroid and cortisol synthesis, developing hypertension, hypokalemia, and absent puberty; heterozygous carriers are asymptomatic but carry reproductive risk

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

CYP17A1 encodes 17α-hydroxylase/17,20-lyase(https://pubmed.ncbi.nlm.nih.gov/14715827/). Without this enzyme, the steroid biosynthesis pathway cannot produce cortisol, androgens, or estrogens. Instead, steroid precursors accumulate and spill into the mineralocorticoid pathway — flooding the body with compounds that...

rs104894797 Pathogenic nonsense variant in dystrophin creating a premature stop codon at position 3182, causing X-linked dilated cardiomyopathy and Duchenne/Becker muscular dystrophy with prominent cardiac involvement

Chromosome X Risk Allele A Category Cardiomyopathy & Structural Heart Tags Cardiovascular, Heart Disease, Muscle, Genetic Counseling, Carrier Status, Arrhythmia

Dystrophin is the largest protein-coding gene in the human genome — 2.3 megabases on the X chromosome, encoding a 427 kDa mechanical scaffolding protein that anchors the interior of muscle cells to the surrounding extracellular matrix. Without functional dystrophin, repeated mechanical stress from muscle contraction...