Research — GeneOps

rs72547511 Rare CYP1A2 missense variant at the critical Pro42 position; nearly abolishes enzyme activity, impairing metabolism of caffeine, clozapine, theophylline, and tizanidine

Chromosome 15 Risk Allele G Category Pharmacogenomics Tags Drug Metabolism, Pharmacogenomics, Caffeine, Cardiovascular, Mental Health

Buried in exon 2 of CYP1A2 lies a single nucleotide change that can reduce the enzyme's activity to less than 1% of normal. The rs72547511 variant — replacing the amino acid proline with arginine at position 42 of the protein — is rare but clinically consequential for anyone who carries it and takes medications that...

rs72823628 Intronic variant in the IL1RL1/IL18R1 receptor gene cluster on chromosome 2q12 that modulates allergic disease susceptibility; carriers of the A allele show reduced risk for allergic rhinitis and atopic conditions

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

When the immune system encounters a harmless pollen grain or a cat hair, the difference between a calm non-reaction and a full allergic cascade often begins at the cell surface, where receptor proteins decide whether to escalate or stand down. The IL1RL1/IL18R1 gene cluster on chromosome 2q12 encodes two closely...

rs6777055 Intronic variant affecting thermal pain sensitivity and central pain signal transmission

Chromosome 3 Risk Allele A Category Neurology & Cognition Tags Pain Sensitivity, Neurotransmitters, Sensory Processing

CACNA2D3 encodes the alpha-2-delta-3 subunit of voltage-gated calcium channels, a critical regulator of how pain signals travel from the thalamus(https://pubmed.ncbi.nlm.nih.gov/21074052/) to higher cortical pain centers. Unlike many pain genes that act in peripheral nerves, CACNA2D3 operates centrally — in the...

rs72547515 Nearly-inactive CYP1A2 missense variant — carriers have severely impaired metabolism of caffeine, theophylline, tizanidine, and other CYP1A2 substrates

Chromosome 15 Risk Allele A Category Pharmacogenomics Tags Drug Metabolism, Pharmacogenomics, Caffeine, Cardiovascular, Carcinogen Metabolism

CYP1A2 is the liver enzyme responsible for clearing approximately 95% of the caffeine you consume, along with clinically critical medications including the muscle relaxant tizanidine, the antipsychotic clozapine, the bronchodilator theophylline, and the antidepressant melatonin. The rs72547515 variant, catalogued as...

rs7927894 Regulatory variant near the EMSY/C11orf30 locus; T allele increases EMSY expression, suppressing filaggrin and ceramide production in skin, and is the broadest known allergic disease risk allele — associated with atopic dermatitis, asthma, hay fever, and the atopic march

Chromosome 11 Risk Allele T Category Allergy & Atopic Disease Tags Autoimmune, Skin, Inflammation, Immune & Autoimmune, Asthma, Skin Health

On chromosome 11q13.5, a single regulatory variant, rs7927894, sits near one of the most consequential genes in allergic disease genetics. The T allele at this position raises expression of EMSY(https://pubmed.ncbi.nlm.nih.gov/14651845/) — and higher EMSY activity turns down the genes that build and maintain the...

rs6795209 Intergenic variant at the HTR1F locus on chromosome 3; the minor A allele increases migraine susceptibility at genome-wide significance and sits within the genomic region encoding the 5-HT1F serotonin receptor — the direct drug target of lasmiditan (Reyvow), the first ditan-class migraine treatment

Chromosome 3 Risk Allele A Category Neurology & Cognition Tags Migraine, Serotonin, Neurotransmitters, Pharmacogenomics, Pain Management, Brain Health

The serotonin system runs through almost every aspect of headache biology. One of its receptors, the 5-HT1F receptor(https://pubmed.ncbi.nlm.nih.gov/35115687/), sits at the exact intersection of genetic migraine susceptibility and modern pharmacology. HTR1F is the direct molecular target of lasmiditan (Reyvow), the...

rs72547516 Rare CYP1A2 missense variant (Ile386Val) associated with potentially reduced enzyme activity and altered metabolism of caffeine, clozapine, theophylline, and other CYP1A2 substrates

Chromosome 15 Risk Allele G Category Pharmacogenomics Tags Drug Metabolism, Pharmacogenomics, Caffeine, Phase I, Carcinogen Metabolism

CYP1A2 is one of the most abundant drug-metabolizing enzymes in the liver, responsible for breaking down approximately 10–15% of clinically used medications, including caffeine(https://pubmed.ncbi.nlm.nih.gov/29282363/), clozapine (antipsychotic), theophylline (asthma), olanzapine, tizanidine, and melatonin. The...

rs7927997 Regulatory variant near C11orf30 (EMSY) on chromosome 11q13.5; the T allele reduces EMSY transcriptional repressor activity, releasing TSLP and CCL5 expression in epithelial cells and increasing susceptibility to eosinophilic inflammation, atopic dermatitis, eosinophilic esophagitis, asthma, poly-sensitization, and Crohn's disease

Chromosome 11 Risk Allele T Category Allergy & Atopic Disease Tags Asthma, Inflammation, Epigenetics, Immune Response, Skin Health, IBD

The C11orf30 gene — commonly known by its protein product name EMSY — sits at one of the most replicated and broadly acting loci in allergy genetics. Variants at this chromosome 11q13.5 locus have been found to influence risk for atopic dermatitis, asthma, hay fever, food allergy, poly-sensitization to multiple...

rs6833641 Intergenic variant near ARAP2 associated with motion sickness susceptibility at genome-wide significance; one of only three loci from the first motion sickness GWAS to also associate with postoperative nausea and vomiting, making it clinically relevant for pre-surgical risk assessment

Chromosome 4 Risk Allele G Category Neurology & Cognition Tags Brain Health, Anesthesia, Sensory Processing, Neurotransmitters, Cognition, Pain Management

Motion sickness is not simply a matter of willpower. The nausea, cold sweats, and vomiting triggered by travel in cars, boats, or aircraft have a substantial heritable component — twin studies estimate heritability at around 57–70%. The first genome-wide association study of motion sickness, published by Hromatka et...

rs72547517 CYP1A2*8 — near-complete loss-of-function missense variant causing severely reduced CYP1A2 enzyme activity; predominantly found in East Asian (Japanese) populations

Chromosome 15 Risk Allele A Category Pharmacogenomics Tags Drug Metabolism, Pharmacogenomics, Caffeine, Ancestry-Specific, Carcinogen Metabolism

CYP1A2(https://pubmed.ncbi.nlm.nih.gov/21989077/) is one of the most clinically relevant drug-metabolizing enzymes in the body. The CYP1A28 allele (rs72547517) is a missense variant that substitutes histidine for arginine at position 456 of the enzyme (p.Arg456His), crippling the enzyme's ability to fold around its...