Friday, July 23, 2021

White paper on assigning LOE to clinical annotations now published

A previous blog post described our new quantitative system for assigning a level of evidence (LOE) to clinical annotations. We are pleased to announce that our white paper about the system has now been published in Clinical Pharmacology and Therapeutics and is available on the PharmGKB website.

The paper details how each piece of evidence linked to a clinical annotation is scored by an algorithm and how the total score of a clinical annotation is translated into a LOE. Use of this system makes the assignment of LOE to be more consistent across clinical annotations and allows users to better understand why a certain LOE has been assigned to a particular clinical annotation.

Further information about scoring of variant annotations and clinical annotations as well as our LOE system can be found on our website.

Monday, June 28, 2021

New PK pathways for drugs on the CPIC gene-drug pairs list

PharmGKB has curated new pathways for the pharmacokinetics of the following drugs that are on the CPIC gene-drug pairs list and either have existing guidelines or are slated for future consideration.  



Inhaled anesthetics:










A complete list of PharmGKB pathways can be found at

Monday, June 14, 2021

CPIC releases guideline for MT-RNR1 and aminoglycosides

The CPIC guideline for aminoglycoside antibiotics and variation in the mitochondrial gene MT-RNR1 has been published in the journal Clinical Pharmacology and Therapeutics.

Aminoglycosides are widely used antibiotics which inhibit protein synthesis in bacteria by binding to the bacterial 16S ribosomal subunit. They are also associated with adverse events, including aminoglycoside-induced hearing loss (AIHL). Patients who carry certain variants in the MT-RNR1 gene, which encodes the 12S ribosomal subunit, are at a greatly increased risk of developing AIHL. These variants cause the 12S subunit to more closely resemble the bacterial 16S subunit, which can lead to aminoglycoside molecules binding to the ribosome and inhibiting protein synthesis. This ultimately results in hearing loss due to cell death in the cochlea.


This is the first CPIC guideline on a mitochondrial gene. As the mitochondrial genome is haploid, rather than diploid, recommendations are given for single variants, rather than for combinations of alleles.


The guideline and supplemental materials are available on the CPIC website. An annotation of the guideline, including interactive genotype picker tool, is available on the PharmGKB website.

Tuesday, June 8, 2021

PharmGKB/CPIC Twitter chat for Healthcare Providers Genomics Education week

PharmGKB and CPIC recently hosted a Twitter chat sharing pharmacogenomics resources as part of NHGRI's Healthcare Providers Genomics Education week (#MedGeneEd21). An archive of the chat is displayed below.

Wednesday, May 12, 2021

Expanded Pharmacokinetics Pathways for PPIs

The Proton Pump Inhibitor Pathway, Pharmacokinetics has been updated and expanded to now highlight four pathways with candidate genes and drug metabolites involved for:

Omeprazole and esomeprazole

Lanzoprazole and dexlansoprazole

Pantoprazole and 


The pathways illustrate the subtle differences between the metabolism of drugs in the class, their different sensitivities to variation in CYP2C19, and aids explanation of the differences in CPIC recommendations for the different drugs (see CPIC Guideline for CYP2C19 and Proton Pump Inhibitor Dosing). 

Monday, May 10, 2021

CPIC seeks feedback for MT-RNR1 terminology

We announced last December that the Clinical Pharmacogenetics Implementation Consortium (CPIC)  was launching its Term Standardization Pharmacogenetic Test Results - Part 2 project.  The project is currently focused on MT-RNR1, as that guideline wraps up.  

The MT-RNR1 Gene/Disease and PGx expert panels have agreed on terminology for MT-RNR1 and aminoglycoside-induced hearing loss for allele clinical function and phenotype.  The final terms are posted for review on the CPIC website.  Please send any feedback to Dr. Kelly Caudle at by May 28th, 2021.

Thursday, May 6, 2021

Rollout of genotype picker tool on DPWG guideline annotations

The allele pull-down menu (also known as the genotype-picker tool) on PharmGKB annotations of CPIC guidelines is an extremely popular feature among users. We are pleased to now expand this functionality to annotations of guidelines from the Royal Dutch Association for the Advancement of Pharmacy - Pharmacogenetics Working Group (DPWG).

The genotype picker tool relies on determining the following information from each guideline:

1. Which alleles are covered by the guideline

2. The assigned functional status of each allele

3. How allele function combinations are mapped to phenotype groups

The DPWG recommendations that are downloadable from the Dutch Pharmacy Organization’s (KNMP) website and annotated on PharmGKB do not typically contain allele functional status or phenotype group mappings. However, this information is often available in KNMP’s ‘gene background’ files which are posted separately.  While DPWG generally follows the same allele-to-phenotype mappings as CPIC, there are some gene-specific differences. These differences mean that all DPWG gene mappings need to be curated into PharmGKB separately from CPIC’s mappings. Our mapping process for each gene covered by DPWG guidelines, including curator notes, can be found here. As we now have internally curated mappings of allele function to phenotype for DPWG, more DPWG guidelines can now be used to support our Level 1A clinical annotations.

Genotype pickers are now available for all annotations of DPWG guidelines with recommendations for HLA-B, CYP2D6 and CYP2C19 genotypes. Work is ongoing to curate DPWG-assigned allele functions and phenotype groups for other genes into PharmGKB. As each gene is curated, genotype pickers will be released on relevant guideline annotation pages.