Research — GeneOps

rs727503493 Frameshift deletion in TMPRSS3 causing premature stop at codon 88; a severe pathogenic allele and Slovenian founder mutation causing DFNB8/10 autosomal recessive sensorineural hearing loss

Chromosome 21 Risk Allele D Category Neurology & Cognition Tags Hearing Loss, Sensorineural, Carrier Status, Congenital, Brain Health

Deep inside the cochlea, thousands of microscopic hair cells convert sound waves into electrical impulses. These cells depend on a molecular guardian called TMPRSS3 — a transmembrane serine protease that is indispensable for their survival from the moment hearing first activates. The c.208delC variant (rs727503493)...

rs776746 Splice site variant creating a non-functional CYP3A5 enzyme, dramatically affecting metabolism of tacrolimus and other immunosuppressants

Chromosome 7 Risk Allele C Category Pharmacogenomics Tags Drug Metabolism, Immunosuppressants, Pharmacogenomics, Transplant

CYP3A5 is a member of the cytochrome P450 superfamily, metabolizing approximately 37% of clinically used drugs(https://pubmed.ncbi.nlm.nih.gov/22982422/). While its close relative CYP3A4 dominates hepatic metabolism, CYP3A5 is the predominant CYP3A enzyme expressed in kidneys, intestines, and other extrahepatic...

rs911263 Intronic proxy variant in RAD51B associated with seropositive rheumatoid arthritis risk; the C allele is protective while the T allele tags a haplotype at the RAD51B locus that predisposes to anti-CCP-positive RA and more severe joint erosion

Chromosome 14 Risk Allele T Category Allergy & Atopic Disease Tags Rheumatoid Arthritis, Arthritis, Autoimmune, DNA Repair, Immune & Autoimmune, Inflammation

The RAD51B gene(https://www.omim.org/entry/602948) encodes a key component of the homologous recombination (HR) machinery. Located at chromosome 14q24.1, RAD51B is most highly expressed in the testis, thymus, ovary, and spleen — tissues that undergo intensive DNA recombination. The variant rs911263 is an intronic...

rs744373 Second strongest genetic risk factor for Alzheimer's disease after APOE, associated with increased tau pathology and accelerated cognitive decline

Chromosome 2 Risk Allele G Category Neurology & Cognition Tags Alzheimer's, Neurological Risk, Memory, Cognitive Decline, Tau Pathology, Brain Health

After APOE ε4(https://pubmed.ncbi.nlm.nih.gov/34978146/), variants in the BIN1 (bridging integrator 1) gene represent the second most significant genetic influence on Alzheimer's disease risk. The rs744373 variant sits in a regulatory region upstream of BIN1 and is associated with an odds ratio of 1.17–1.19 for...

rs8099917 Intergenic variant upstream of IFNL3 — second major IL28B locus predictor of hepatitis C spontaneous clearance and treatment response, with independent predictive value over rs12979860 in Asian populations

Chromosome 19 Risk Allele G Category Pharmacogenomics Tags Innate Immunity, Inflammation, Infectious Disease, Interferon, Immune & Autoimmune, Drug Metabolism

Eight kilobases upstream of the interferon lambda-3 gene (IFNL3, formerly IL28B) on chromosome 19q13.13 sits a T/G polymorphism that has shaped how hepatitis C is treated across the world. The rs8099917 variant lies in the intergenic region between IFNL2 and IFNL3 and, like its more famous neighbour rs12979860, tags...

rs9275596 Intergenic tag SNP between HLA-DQB1 and HLA-DQA2 tagging the HLA-DQA1*01:02 risk haplotype; the C allele confers ~1.7-fold increased susceptibility to peanut allergy and is associated with multiple sclerosis risk

Chromosome 6 Risk Allele C Category Allergy & Atopic Disease Tags Autoimmune, HLA, Food Sensitivity, Immune Response, Inflammation

The human immune system must constantly distinguish harmless proteins from genuine threats. At the centre of this process is the HLA (Human Leukocyte Antigen) class II system(https://pmc.ncbi.nlm.nih.gov/articles/PMC5665015/), which determines which protein fragments the immune system learns to tolerate and which it...

rs75932628 Rare missense variant in microglial receptor TREM2 that significantly increases late-onset Alzheimer's disease risk through impaired microglial function and amyloid clearance

Chromosome 6 Risk Allele T Category Neurology & Cognition Tags Alzheimer's, Neurological Risk, Neuroinflammation, Aging, Cardiovascular

TREM2 (Triggering Receptor Expressed on Myeloid cells 2) is a cell surface receptor found exclusively on microglia, the brain's resident immune cells. Microglia act as the brain's surveillance system(https://pubmed.ncbi.nlm.nih.gov/23150934/). The R47H variant, discovered in two landmark 2013 studies published...

rs8192780 Downstream regulatory variant near CYP2E1 associated with nasopharyngeal carcinoma risk in smokers through altered carcinogen metabolism

Chromosome 10 Risk Allele T Category Pharmacogenomics Tags Pharmacogenomics, Drug Metabolism, Carcinogen Metabolism, Cancer Risk, Liver, Smoking Related

CYP2E1 is the liver and lung enzyme that metabolizes ethanol, acetaminophen, and a wide spectrum of environmental carcinogens including tobacco-specific nitrosamines (NNK), polycyclic aromatic hydrocarbons, benzene, and chlorinated solvents. rs8192780 sits approximately 1.5 kilobases downstream of the CYP2E1 gene in...

rs950881 Intronic variant in the IL1RL1 gene on chromosome 2q12 encoding the ST2 receptor for IL-33; the T allele is associated with reduced allergic rhinitis risk, particularly in males, by modulating IL-33/ST2 signaling amplitude

Chromosome 2 Risk Allele G Category Allergy & Atopic Disease Tags Asthma, Innate Immunity, Inflammation, Immune Response, Immune Function, Respiratory Infections

The IL1RL1 gene encodes ST2(https://pubmed.ncbi.nlm.nih.gov/38821053/), the primary receptor for the alarmin cytokine IL-33. Positioned on chromosome 2q12 — the most replicated genetic locus for atopic disease in the human genome — IL1RL1 sits in a dense cluster of interleukin-1 receptor family genes that...

rs76763715 GBA missense variant (p.Asn409Ser, formerly N370S) — the most common GBA pathogenic allele; heterozygotes carry substantially elevated risk for Parkinson's disease, Lewy body dementia, and REM sleep behavior disorder; homozygotes develop Gaucher disease type I

Chromosome 1 Risk Allele C Category Neurology & Cognition Tags Parkinson's, Neurodegeneration, Neurological Risk, Dementia, Autophagy, Sleep

Inside every cell, lysosomes act as the cellular recycling plant, breaking down worn-out proteins and glycolipids. Glucocerebrosidase (GCase)(https://omim.org/entry/606463) that turns out to have profound consequences for brain health. The p.Asn409Ser variant (formerly called N370S in older nomenclature) is the most...