Research — GeneOps

rs1635501 Intronic variant in EXO1 (exonuclease 1), a DNA mismatch repair and meiotic recombination enzyme; each copy of the C allele is associated with approximately 10 fewer weeks before natural menopause onset, implicating impaired oocyte DNA repair in accelerated follicle depletion

Chromosome 1 Risk Allele C Category Gamete Quality & DNA Repair Tags Ovarian Reserve, Fertility, Reproductive Health, Menopause, DNA Repair, Mismatch Repair

The timing of natural menopause is one of the most heritable aspects of female reproductive biology, with an estimated heritability of 50–60%. Genome-wide association studies have repeatedly converged on the same biological theme: DNA repair genes dominate the genetic landscape of ovarian aging. Among these, EXO1...

rs16930609 Upstream regulatory variant in CYP2R1 that tags a haplotype associated with reduced hepatic vitamin D 25-hydroxylation efficiency and lower circulating 25(OH)D levels

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

Vitamin D from sunlight or diet is biologically inert until activated by two sequential hydroxylation steps in the liver and kidneys. The first step — the conversion of vitamin D3 to 25-hydroxyvitamin D (25(OH)D)() — is performed primarily by the enzyme CYP2R1 (cytochrome P450 family 2 subfamily R member 1),...

rs1799793 Missense variant in the XPD helicase that reduces nucleotide excision repair fidelity, modestly increasing susceptibility to UV-induced and carcinogen-induced DNA damage across multiple cancer types

Chromosome 19 Risk Allele T Category Cancer Risk Tags Cancer Risk, DNA Repair, Cancer Screening, Smoking Interaction

Your cells face thousands of DNA-damaging events every day. Ultraviolet radiation creates bulky pyrimidine dimers, tobacco smoke deposits polycyclic aromatic hydrocarbon adducts, and industrial chemicals leave behind covalent modifications that distort the double helix. The primary pathway for repairing all of these...

rs1805123 Common KCNH2 missense variant that alters hERG potassium channel kinetics, shortens cardiac repolarization in homozygotes, and modifies susceptibility to QT-prolonging drugs and arrhythmias

Chromosome 7 Risk Allele G Category Arrhythmia & Heart Rhythm Tags Arrhythmia, Cardiovascular, Heart Disease, Drug Response, Pharmacogenomics

The hERG channel (Kv11.1)(https://pubmed.ncbi.nlm.nih.gov/12829173/) is one of the most drug-sensitive ion channels in the human heart. Its blockade — a frequent off-target effect of drugs across dozens of pharmacological classes — is the dominant mechanism of acquired long QT syndrome. Within this gene, the K897T...

rs198968 Intronic variant in kallikrein-related peptidase 4 gene affecting KLK4 expression during enamel maturation and susceptibility to dental caries in primary dentition

Chromosome 19 Risk Allele G Category Dental & Oral Health Tags Dental & Oral Health, Enamel Health, Minerals, Calcium, Inflammation

Tooth enamel begins life as a soft, protein-rich matrix laid down by specialized cells called ameloblasts. The hard mineral — hydroxyapatite — crystallizes within this scaffold, but the scaffold itself must be completely removed before the crystals can interlock and form the hardest biological tissue in the human...

rs10405121 Common intronic variant in CACNA1A — the P/Q-type calcium channel gene mutated in familial hemiplegic migraine — that reaches genome-wide significance for migraine with aura; the G (reference) allele confers typical susceptibility while the A allele is mildly protective

Chromosome 19 Risk Allele G Category Neurology & Cognition Tags Migraine, Calcium, Brain Health, Pain Sensitivity, Neurological Risk, Cardiovascular

CACNA1A(https://pubmed.ncbi.nlm.nih.gov/35115687/) is one of the best-characterised neurological genes in genetics. Rare, highly penetrant mutations in this gene cause three distinct Mendelian disorders: familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2), and spinocerebellar ataxia type 6...

rs104894005 Pathogenic glucokinase nonsense variant introducing a premature stop codon that abolishes protein function, causing autosomal dominant maturity-onset diabetes of the young type 2 (MODY2) in heterozygous carriers — the original nonsense mutation in GCK identified in 1992

Chromosome 7 Risk Allele A Category Blood Sugar & Diabetes Tags Diabetes, Insulin, Metabolic, Genetic Counseling, Carrier Status, Energy Metabolism

In 1992, a French research team identified the first nonsense mutation in the glucokinase gene and, in doing so, answered a decades-old question: why do some families pass down mild diabetes through every generation as if it were hair colour? The answer was an amber stop codon — a single nucleotide change (c.835GT)...

rs104894141 Rare pathogenic nonsense variant in CYP17A1 causing complete abolition of 17α-hydroxylase/17,20-lyase activity; homozygotes develop the full 17α-hydroxylase deficiency phenotype (hypertension, hypokalemia, absent puberty, low cortisol), while heterozygous carriers are clinically unaffected but carry a CYP17A1 loss-of-function allele relevant to reproductive planning.

Chromosome 10 Risk Allele T Category Reproductive Hormones Tags Steroid Hormones, Steroid Metabolism, Hypertension, Reproductive Health, Carrier Status, Congenital

The human body's ability to make cortisol, estrogens, and androgens all runs through a single enzymatic checkpoint: CYP17A1, or cytochrome P450 17α-hydroxylase/17,20-lyase(https://pubmed.ncbi.nlm.nih.gov/8070426/). The rs104894141 variant introduces a premature stop codon at the very beginning of this protein —...

rs104894664 Rare pathogenic TTR missense variant causing hereditary transthyretin amyloidosis with predominantly central nervous system and oculoleptomeningeal involvement

Chromosome 18 Risk Allele A Category Cardiomyopathy & Structural Heart Tags Amyloidosis, Cardiovascular, Neurodegeneration, Neuropathy, Genetic Counseling, Inflammation

Transthyretin (TTR) is a tetrameric transport protein produced mainly in the liver and choroid plexus that carries thyroxine and retinol-binding protein through the bloodstream and cerebrospinal fluid. In healthy individuals, four identical TTR subunits lock together into a stable tetramer. In hereditary TTR...

rs1049742 Missense variant in the diamine oxidase enzyme that contributes to reduced histamine clearance from dietary sources

Chromosome 7 Risk Allele T Category Methylation & Detox Tags Histamine, Food Sensitivity, Detoxification, Methylation & Detox, Gut Health

Every meal containing aged cheese, cured meat, fermented foods, or a glass of wine delivers a histamine load to your gut. For most people this goes unnoticed — the diamine oxidase (DAO) enzyme(https://www.ncbi.nlm.nih.gov/gene/26) neutralises it before it can enter circulation. But for carriers of certain AOC1...