Pharmacogenomics

GLP-1 receptor signal peptide variant that enhances semaglutide and tirzepatide weight loss efficacy but increases nausea and vomiting risk

Rare protective missense variant in the GLP-1 receptor associated with lower fasting glucose, reduced T2D risk, and coronary heart disease protection

Intronic CYP2B6 haplotype-tagging variant associated with altered plasma concentrations of efavirenz, S-methadone, and other CYP2B6-metabolized drugs

GLP-1 receptor variant in intracellular loop 2 that alters receptor surface expression and signaling, influencing antipsychotic response and cortisol regulation

Synonymous variant in P-glycoprotein affecting drug efflux pump expression and hundreds of substrate drugs

No-function CYP2C9 variant with major warfarin implications

CYP2C8 3-prime UTR variant associated with cardiovascular risk via altered epoxyeicosatrienoic acid metabolism and hydroxychloroquine-related renal adverse effects

Decreased function CYP2D6 variant common in Asian populations

No-function variant causing deficient thiopurine methylation; most common TPMT deficiency allele in East Asian and African populations

Nucleotide diphosphatase that inactivates toxic thiopurine metabolites; reduced function causes severe myelosuppression at standard drug doses

Missense variant in IFNL4 exon 2 that reduces IFN-λ4 protein activity; the Ser70 form (A allele) produces weaker antiviral signalling and is associated with better hepatitis C clearance among ΔG carriers

Increased function CYP2C19 variant - rapid/ultrarapid metabolizer

Intronic variant in IFNL4 — the strongest host genetic predictor of hepatitis C spontaneous clearance and treatment response, controlling interferon lambda antiviral immunity

Downstream variant near IFNL3 — third IL28B locus predictor of hepatitis C spontaneous clearance and treatment response; preferred tag for HCV pharmacogenomics in Asian populations where it was the original GWAS discovery signal

Intronic CYP2C8 haplotype-tagging variant linked to bisphosphonate-related osteonecrosis of the jaw risk

Intronic CYP2C8 variant tagging a haplotype associated with altered taxane drug clearance and survival outcomes in chemotherapy-treated patients

Common CYP2D6 variant defining the *2 allele; previously considered normal-function but recent evidence shows reduced expression through altered splicing

Synonymous CYP2D6 variant that causes allele dropout in standard CYP2D6*3 genotyping assays, potentially masking co-inherited non-functional alleles

Decreased function variant affecting warfarin, phenytoin, and NSAIDs

Mu-opioid receptor variant affecting opioid response and pain sensitivity

Decreased-function variant causing reduced thiopurine methylation; pairs with TPMT*3C on the same chromosome to form the TPMT*3A haplotype, the most common cause of TPMT deficiency in Europeans

Intronic CYP2C8 variant associated with paclitaxel-induced toxicity and bisphosphonate-related osteonecrosis risk in multiple myeloma

Intronic CYP2C8 variant linked to hypertension susceptibility, COPD risk, and bladder cancer protection

Deep intronic CYP2C9 variant associated with altered drug response

Intronic CYP2C9 haplotype tag associated with altered warfarin sensitivity and NSAID metabolism in Asian populations

Intronic CYP2C8 variant associated with bisphosphonate-related jaw complications and clopidogrel response

Promoter variant increasing CYP2E1 inducibility, elevating oxidative stress from ethanol and procarcinogen metabolism

Intronic CYP1A2 variant near the 5' end; G allele is associated with altered metabolic ratios for CYP1A2 substrates including escitalopram

Reduces vitamin K metabolism, requiring higher warfarin doses to achieve anticoagulation

Reduces ABCG2 transporter function affecting rosuvastatin levels and uric acid excretion, increasing risk for statin side effects and gout

Intronic CYP3A4 variant associated with altered drug clearance, affecting metabolism of methadone, cyclosporine, and other CYP3A4 substrates

Intronic variant in CYP2J2

Intronic variant in MATE1, the renal and hepatic metformin efflux transporter; the A allele reduces tubular secretion, prolongs metformin retention, and enhances glucose-lowering response in type 2 diabetes

3' UTR variant that increases CYP2E1 expression, raising hepatotoxicity risk from acetaminophen, ethanol, and occupational solvents

Synonymous exon-8 variant that reduces CYP2E1 mRNA and protein expression, altering metabolism of acetaminophen, isoniazid, ethanol, and volatile anesthetics

Promoter variant affecting CYP3A4 expression, most common in African populations

Decreased-function CYP2D6 allele common in African populations, reducing metabolism of antidepressants, antipsychotics, opioids, and tamoxifen

Intronic splice variant causing decreased CYP2D6 enzyme activity through aberrant splicing

Promoter variant that reduces CYP2A6 expression by ~50%, slowing nicotine metabolism and altering response to several cancer and antiretroviral drugs

Reduces OCT2 organic cation transporter function in the kidney, lowering metformin renal clearance and conferring partial protection against cisplatin ototoxicity and nephrotoxicity

Intronic splice variant causing ~50% reduced CYP3A4 mRNA expression, affecting metabolism of ~50% of all prescription drugs

Near-complete loss-of-function CYP2B6 variant causing severely impaired metabolism of efavirenz, bupropion, methadone, and other CYP2B6 substrates

Decreased-function variant affecting metabolism of efavirenz, methadone, bupropion, and cyclophosphamide

Missense variant in the GLP-1 receptor that alters drug response to GLP-1 agonists (Ozempic, Wegovy, Saxenda) and DPP-4 inhibitors, with genome-wide significant protection against type 2 diabetes in East Asians

Intronic variant in KDM4A histone demethylase associated with problematic opioid prescription use in a 132,113-participant GWAS

Upstream CYP2C19 variant associated with altered R-warfarin clearance

Most critical pharmacogenomic variant causing complete loss of DPD enzyme function; increases fatal 5-FU/capecitabine toxicity risk without dose reduction

Phase II glucuronidation enzyme that metabolizes bilirubin and many drugs including irinotecan; reduced activity causes Gilbert syndrome and severe chemotherapy toxicity

Statin transport - affects muscle side effect risk with statins

No-function CYP2C19 variant affecting PPIs, clopidogrel, and some antidepressants

3' untranslated region variant in IFNL3 (IL28B) that controls mRNA stability via AU-rich elements and miRNA binding — predicts hepatitis C spontaneous clearance and treatment response

No-function CYP2C19 stop-gain variant — second most common loss-of-function allele, highest in East Asian ancestry

Missense variant reducing CYP3A4-mediated nifedipine clearance, causing elevated exposure to statins and other CYP3A4 substrates in heterozygous carriers

No-function DPYD star allele (I560S) causing severe DPD deficiency; one of four CPIC high-priority variants requiring 50% fluoropyrimidine dose reduction

CYP2E1*3 missense variant with no demonstrated change in enzyme activity

Synonymous exon-11 tag SNP for the DPYD HapB3 haplotype; benign on its own but in near-complete linkage with the causal deep intronic splice variant rs75017182 that causes ~50% DPD activity loss

Intronic variant in EIPR1 (endosomal trafficking protein) associated with pain sensitivity

Factor V Leiden - blood clotting disorder affecting thrombosis risk

Intronic variant in the OCT1 organic cation transporter reducing hepatic metformin uptake and altering response to multiple cation-transported drugs

Intergenic variant near LRRIQ3 associated with problematic opioid prescription use in a large GWAS; the T allele tags elevated risk of using opioids not as prescribed

Missense variant (Val179Ile) defining the CYP2E1*4 allele

Alcohol metabolism - flush reaction and cancer risk

Rare missense variant in CYP3A4 that reduces protein expression and enzymatic activity across multiple drug substrates

GLP-1 receptor variant that alters response to GLP-1 agonist medications used for weight loss and type 2 diabetes

Intronic CYP2D6 haplotype tag variant (rs28371702 canonical form) associated with altered drug metabolism ratios for CYP2D6 substrates including aripiprazole and praziquantel

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

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

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

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.

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

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

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

Warfarin sensitivity - determines initial dosing