Research — GeneOps

rs72709458 Intronic TERT variant that increases uterine fibroid (leiomyoma) risk through impaired telomere maintenance and genome stability, independent of the longevity TERT variants

Chromosome 5 Risk Allele T Category Endometriosis & Uterine Health Tags Fertility, Reproductive Health, Women's Health, Cancer Risk

Uterine fibroids (leiomyomas) are benign smooth-muscle tumors of the uterus that affect up to 70% of women by age 50. While they are common, their underlying biology is clonal — each fibroid arises from a single cell that escapes normal growth control. A genome-wide association study of more than 400,000 women in...

rs763361 Missense variant in the T-cell and NK-cell co-stimulatory receptor CD226 (DNAM-1) that raises the activation threshold of adaptive immunity and confers risk for multiple autoimmune diseases including type 1 diabetes, multiple sclerosis, SLE, and rheumatoid arthritis

Chromosome 18 Risk Allele T Category Autoimmune Tolerance & T-Cell Regulation Tags Autoimmune, T-Cell Regulation, Type 1 Diabetes, Multiple Sclerosis, Immune & Autoimmune, Rheumatoid Arthritis

CD226 (also called DNAM-1, DNAX Accessory Molecule-1)(https://www.ncbi.nlm.nih.gov/gene/10666) occupies a central position in both antitumour immunity and autoimmune regulation. rs763361 is a missense variant in exon 7 of CD226 on chromosome 18q22 that substitutes glycine for serine at protein position 307. Unlike...

rs7746808 Intergenic variant near the IL23A locus associated with psoriasis and psoriatic arthritis susceptibility through the IL-23/Th17 inflammatory axis

Chromosome 6 Risk Allele C Category Psoriasis & Spondyloarthropathy Tags Immune & Autoimmune, Psoriasis, Inflammation, Biologic Therapy, Skin, Inflammatory Bowel Disease

Interleukin-23(https://www.omim.org/entry/605580) is one of the master regulators of chronic autoimmune inflammation. IL-23 is produced by dendritic cells and macrophages responding to bacterial pathogens and tissue damage signals, and its primary function is to expand and maintain Th17 cells. rs7746808 is an...

rs9340799 Intronic variant in the estrogen receptor alpha gene (intron 1) associated with endometriosis-related infertility, IVF outcomes, severe pre-eclampsia risk, and ovarian reserve; the G allele increases endometriosis-related reproductive risk while showing some population-specific protective effects for fractures and male fertility

Chromosome 6 Risk Allele G Category Reproductive Hormones Tags Endometriosis, Estrogen, Fertility, Reproductive Health, Women's Health, IVF

Estrogen receptor alpha (ERα), encoded by ESR1 on chromosome 6, is the master mediator of estrogen signaling across reproductive tissues, bone, brain, and the cardiovascular system. When estrogen binds ERα, the receptor dimerizes, translocates to gene promoters, and drives transcription of hundreds of downstream...

rs17250932 Upstream promoter variant in TBX21 that reduces neonatal IL-5 and IL-13 secretion after innate immune stimulation; the minor C allele dampens Th2 cytokine output at birth, suggesting a role in early-life immune programming and atopic susceptibility through reduced TBX21 transcriptional drive

Chromosome 17 Risk Allele T Category Allergy & Atopic Disease Tags Asthma, T-Cell Regulation, Inflammation, Immune Response, Skin Health, Autoimmune

The TBX21 gene encodes T-bet, the master transcription factor that drives naive CD4+ T cells toward the Th1 differentiation path(https://pubmed.ncbi.nlm.nih.gov/22303482/). rs17250932 is a single-nucleotide variant situated approximately 1.5 kilobases upstream of the TBX21 transcription start site in the promoter...

rs1784931 Intronic variant in the sortilin-related receptor that tags a 3′ haplotype block linked to reduced SORL1 brain expression; the A allele is associated with lower receptor levels and modestly increased Alzheimer's disease risk

Chromosome 11 Risk Allele A Category Neurology & Cognition Tags Alzheimer's, Neurodegeneration, Dementia, Cognition, Brain Health, Aging

Every neuron in your brain constantly recycles its membrane proteins through a network of intracellular sorting stations called endosomes. One of the most important proteins cycling through this network is APP — amyloid precursor protein — the molecule whose misprocessing produces the sticky amyloid-beta plaques...

rs1800909 Signal-peptide missense variant that alters GGH subcellular targeting; C allele carriers show modestly lower plasma homocysteine and altered methotrexate pharmacokinetics

Chromosome 8 Risk Allele G Category Methylation & Detox Tags Methylation, Folate, B Vitamins, Homocysteine, Detoxification

Every folate molecule entering a cell faces the same fate: to be useful, it must be trapped. Cells accomplish this by adding chains of glutamate — called polyglutamate tails() — that anchor folate inside the cell. GGH (gamma-glutamyl hydrolase) is the enzyme that removes these tails, converting retained...

rs1800961 Missense variant in HNF4A causing hepatocyte-specific loss of transcriptional activity; associated with early-onset type 2 diabetes and metabolic syndrome, particularly in Latino and Asian populations

Chromosome 20 Risk Allele T Category Blood Sugar & Diabetes Tags Diabetes, Insulin, Metabolic, Liver Health, Insulin Resistance, Metabolic Syndrome

HNF4A(https://pubmed.ncbi.nlm.nih.gov/8945471/). The Thr130Ile variant (T130I) substitutes threonine for isoleucine at position 130 in the DNA-binding domain — a domain so conserved it is essentially identical across vertebrates. The result is a partial, tissue-selective loss of transcriptional activity that affects...

rs2070672 CYP2E1 promoter variant affecting enzyme expression and susceptibility to acetaminophen hepatotoxicity, alcohol-induced liver injury, and drug-induced hepatotoxicity

Chromosome 10 Risk Allele G Category Pharmacogenomics Tags Drug Metabolism, Pharmacogenomics, Liver, Liver Health, Alcohol, Carcinogen Metabolism

CYP2E1 is a cytochrome P450 enzyme(https://www.ncbi.nlm.nih.gov/gene/1571) responsible for metabolizing ethanol, acetaminophen, volatile organic compounds, and several anesthetic agents including sevoflurane and isoflurane. A key variant in its upstream promoter region — rs2070672 (historically the RsaI/PstI...

rs225014 Affects conversion of inactive T4 to active T3 thyroid hormone in brain, pituitary, and peripheral tissues

Chromosome 14 Risk Allele C Category Hormones & Sleep Tags Hormones & Thyroid, Neurotransmitters, Metabolism, Mood, Fatigue

Your thyroid gland secretes mostly T4 (thyroxine), an inactive prohormone that must be converted to T3 (triiodothyronine) to exert biological effects. This conversion happens locally in tissues(https://pubmed.ncbi.nlm.nih.gov/19190113/) via the type 2 deiodinase (DIO2) enzyme. The Thr92Ala variant changes a...