Research — GeneOps

rs8111930 Intronic variant in MRPL4 on chromosome 19p13.2 that alters transcription factor binding (AREB6 loss, CREB2 gain), reducing mitochondrial ribosomal protein L4 expression and increasing susceptibility to atopy and allergic rhinitis via the HIF-1α signalling pathway

Chromosome 19 Risk Allele G Category Allergy & Atopic Disease Tags Asthma, Inflammation, Immune Function, Mitochondria, Immune System, Lung Health

Most people carry the common G allele at rs8111930 — the majority genotype — yet it is also the allele that marginally tips the immune balance toward atopic sensitisation. This variant sits in an intron of MRPL4(https://www.ncbi.nlm.nih.gov/gene/51073), located on chromosome 19p13.2 near the gene for ICAM-1...

rs6897932 Splicing variant in the IL-7 receptor alpha chain that shifts the balance toward soluble receptor, amplifying IL-7 signaling and raising susceptibility to multiple sclerosis and related autoimmune conditions

Chromosome 5 Risk Allele C Category Neurology & Cognition Tags Immune & Autoimmune, Multiple Sclerosis, T-Cell Regulation, Inflammation, Immune & Gut, Autoimmune, Immune System, Neurological Risk

Interleukin-7 (IL-7) is an indispensable cytokine for T-cell development and homeostasis. Without adequate IL-7 signaling, the thymus cannot export naïve T cells(https://pubmed.ncbi.nlm.nih.gov/17660817/) and the peripheral T-cell pool shrinks. IL-7 acts through its receptor, IL-7Rα (CD127), encoded by the IL7R gene...

rs72549354 Frameshift insertion creating a null CYP2D6 allele; carriers cannot metabolize ~25% of common drugs including opioids, antidepressants, and antipsychotics

Chromosome 22 Risk Allele D Category Pharmacogenomics Tags Drug Metabolism, Pharmacogenomics, Pain Medication, Antidepressants, Mental Health

CYP2D6 is one of the most pharmacologically important enzymes in the human body, responsible for metabolizing approximately 25% of all commonly prescribed drugs — spanning psychiatry, oncology, pain management, and cardiology. The CYP2D620 allele(https://www.ncbi.nlm.nih.gov/snp/rs72549354) is a rare null allele...

rs872129 Third independent eQTL signal at the CHI3L1/YKL-40 locus on chromosome 1q32.1; the G allele modifies circulating YKL-40 levels independently of the two primary CHI3L1 regulatory variants and has been linked to altered inflammatory and cerebrovascular risk

Chromosome 1 Risk Allele G Category Allergy & Atopic Disease Tags Asthma, Inflammation, Biomarkers, Immune & Autoimmune, Lung Health, Cardiovascular

The CHI3L1 gene encodes YKL-40, a 40-kDa secreted glycoprotein produced by macrophages, neutrophils, and epithelial cells during inflammation. Elevated circulating YKL-40 marks active tissue remodeling and chronic inflammation — it is elevated in asthma, COPD, rheumatoid arthritis, coronary artery disease, and...

rs7101429 Intronic variant in GAB2 that modulates late-onset Alzheimer's disease risk; the minor G allele is protective, associated with higher GAB2 expression and reduced tau and amyloid pathology in brain tissue

Chromosome 11 Risk Allele A Category Neurology & Cognition Tags Alzheimer's, Tau Pathology, Neurodegeneration, Cognitive Decline, Neuroprotection, Brain Health

GAB2 (GRB2-associated-binding protein 2)(https://pubmed.ncbi.nlm.nih.gov/17553421/) encodes a key node in the PI3K/AKT signaling cascade. In neurons, this pathway regulates the activity of GSK-3β (glycogen synthase kinase-3 beta)(https://pubmed.ncbi.nlm.nih.gov/17553421/). The rs7101429 variant sits deep within an...

rs75017182 Deep intronic splice-site variant that is the functional driver of the DPYD HapB3 haplotype; creates a cryptic splice site causing ~50% DPD activity loss and requiring 50% fluoropyrimidine dose reduction

Chromosome 1 Risk Allele C Category Pharmacogenomics Tags Drug Metabolism, Pharmacogenomics, Chemotherapy, Cancer Treatment, Fluoropyrimidine Toxicity, Pyrimidine Catabolism

DPYD encodes dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme(https://pubmed.ncbi.nlm.nih.gov/29152729/) that breaks down fluoropyrimidine chemotherapy drugs. DPYD HapB3 is one of only four DPYD variants that CPIC designates as clinically actionable(https://pubmed.ncbi.nlm.nih.gov/29152729/) before...

rs8832 3' untranslated region variant in the IL-4 receptor alpha chain gene; the G allele is associated with elevated type-2 inflammatory endotype in asthma and predicts exacerbation risk and pharmacogenetic response to IL-4 pathway blockade

Chromosome 16 Risk Allele G Category Allergy & Atopic Disease Tags Asthma, Inflammation, Immune Response, Immune System, Skin Health

Interleukin-4 (IL-4) is the master switch for Th2 immune polarization — the immune phenotype that underlies asthma, atopic dermatitis, and allergic rhinitis. Its receptor, encoded by IL4R at chromosome 16p12.1(https://www.ncbi.nlm.nih.gov/gene/3566), amplifies or moderates the Th2 signal depending on which alleles a...

rs72474224 Connexin 26 missense variant causing partial loss of cochlear gap junction function; the leading cause of mild-to-moderate hereditary hearing loss in East Asian populations

Chromosome 13 Risk Allele T Category Neurology & Cognition Tags Hearing Loss, Sensorineural, Congenital, Carrier Status, Sensory Processing

The cochlea — the spiral hearing organ of the inner ear — depends on a precise ionic environment to convert sound waves into electrical nerve signals. Connexin 26, encoded by GJB2(https://www.ncbi.nlm.nih.gov/gene/2706) forms the molecular channels that maintain this environment. The V37I variant (rs72474224,...

rs762551 CYP1A2 *1F intronic inducibility variant — defines fast vs slow caffeine metabolizer status and affects clearance of clozapine, theophylline, and tizanidine. The slow-metabolizer C allele blunts the smoking-induced enzyme upregulation that normally accelerates these drugs in heavy smokers.

Chromosome 15 Risk Allele C Category Pharmacogenomics Tags Drug Metabolism, Diet, Cardiovascular

CYP1A2 is the enzyme responsible for metabolizing approximately 95% of caffeine in the body. Your CYP1A2 genotype largely determines whether you are a "fast" or "slow" caffeine metabolizer, which has implications not just for how coffee affects you but potentially for your cardiovascular health. The Mechanism The...

rs907091 A 3'UTR variant in IKZF3 that alters miR-326 binding affinity, reducing Aiolos transcription factor expression in a T-allele-dependent manner and increasing susceptibility to systemic autoimmune disease through impaired B-cell maturation and immune homeostasis

Chromosome 17 Risk Allele T Category Allergy & Atopic Disease Tags Autoimmune, B-Cell Signaling, Immune System, Lupus, Rheumatoid Arthritis, Inflammation

IKZF3 encodes Aiolos, a zinc finger transcription factor in the Ikaros family that acts as a guardian of immune homeostasis. Aiolos is expressed throughout lymphocyte development and plays essential roles in B-cell maturation, plasma cell differentiation, and — crucially — suppression of aberrant autoimmune...