Friday, June 14, 2024

The PharmGKB Blog has transitioned to the ClinPGx Blog


We have a brand new blog platform: the ClinPGx Blog.

PharmGKB, CPIC and PharmCAT are transitioning to a unified resource under the ClinPGx umbrella and will subsequently publish news to the ClinPGx Blog. This is the last post made on this blog site; all future posts will be found on If you subscribe to announcements from the PharmGKB Blog, your subscription will be migrated to the new system automatically. You’ll also get the opportunity to sign up for announcements from other ClinPGx projects. More details are available on the ClinPGx Blog.

New blog posts will only appear on the ClinPGx Blog and previous PharmGKB Blog posts are also accessible there, so all posts can be obtained from one place. The PharmGKB Blog will remain online (but not updated) for as long as Blogger will allow. That means existing links to PharmGKB Blog posts will be maintained.

Thank you for your continued interest in PharmGKB, CPIC, PharmCAT and all the other projects we have written about on this blog. We are excited to keep sharing our work with you on the new ClinPGx Blog!

Friday, May 10, 2024

PharmGKB data now available in OpenTargets

Data from PharmGKB clinical annotations are now integrated into OpenTargets; a free online tool which brings together data from publicly available datasets to help prioritize potential drug targets.

The Pharmacogenetics section of the profile for both drugs and targets (genes) now shows information from PharmGKB clinical annotations, including the phenotype category and the Level of Evidence. By hovering over the question mark next to the phenotype, the full text of one phenotype description from the clinical annotation can be displayed, as in these images for OPRM1.

Information from toxicity-related clinical annotations is now also displayed in the Safety section for targets, as shown for HLA-A below.

We’re excited to be involved with OpenTargets’ work and hope to be able to integrate more data from PharmGKB in the future. For more information, visit the OpenTargets blog.

Friday, March 29, 2024

Update to the CPIC Guideline for Thiopurines Regarding Dual TPMT and NUDT15 Intermediate Metabolizers

CPIC has updated guidance for patients who are both TPMT and NUDT15 Intermediate Metabolizers from "Clinical Pharmacogenetics Implementation Consortium Guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 Update". From the CPIC website:

"At the time of guideline publication, the extent of reduction for thiopurines recommended for patients with intermediate metabolism for both TPMT and NUDT15 was unclear. A recent publication (PMID: 38230823) found that these individuals need a substantial dose reduction to mitigate toxicity in TPMT/NUDT15 IM/IM patients. The recommendation for a TPMT intermediate metabolizer/NUDT15 intermediate metabolizer has been updated for all thiopurines to recommend a starting dose at 20%-50% of normal dosages, depending on the starting dose. See here for updated recommendation tables (azathioprine, mercaptopurine, thioguanine). The pre- and post-test alert tables have been updated accordingly."

Please find the new wording and tables on the PharmGKB guideline annotations for azathioprine, mercaptopurine and thioguanine.  The CPIC database and website have also been updated.

Monday, March 18, 2024

PharmCAT Tutorial Videos Now Available on YouTube

Pharmacogenomics Clinical Annotation Tool (PharmCAT) tutorial videos are now available on the PharmGKB YouTube channel. The tutorial videos provide clear, step-by-step instructions for running PharmCAT from command lines. By providing genotype-based drug prescribing recommendations, we hope to engage the wider genomics community and create a standard for the use in precision medicine.

The first two videos cover (1) the introduction to PharmCAT, modules, and reports and (2) a hands-on example that walks you through the setup and commands for running PharmCAT.

Future videos will cover how to supply external pharmacogenomic calls to PharmCAT, how to use ‘Research’ modes, how to use the PharmCAT functionalities for biobank-scale analyses, and more.
More information about PharmCAT can be found at To follow PharmCAT, subscribe to the PharmGKB YouTube channel for new videos or the PharmCAT mailing list for the latest PharmCAT updates.

If you have questions regarding PharmCAT, please contact us at

Thursday, March 14, 2024

NAT2 now released on PharmVar

PharmVar and PharmGKB are excited to share that NAT2 has been transitioned into the PharmVar database and updated accordingly on PharmGKB. NAT2 metabolizes several pharmaceutical substrates, including isoniazid, hydralazine, amifampridine, procainamide and sulfonamides, as well as some highly carcinogenic arylamines. NAT2 enzymatic activity varies considerably between individuals, due to polymorphisms in NAT2 coding sequence that may be found more commonly in some populations than others. NAT2 alleles usually contain more than one single nucleotide variation (SNV), with specific variants defining different allelic groups. Given the complex haplotypic nature of NAT2 alleles, phasing of SNVs to determine diplotype from genotype can be difficult. It is therefore important to maintain up-to-date information regarding sequence variation and star allele (haplotype) definitions to facilitate accurate genetic testing, genotype interpretation and phenotype prediction in the research and clinical settings.

Some drastic changes have been made to NAT2 nomenclature during transition from the original Database of Arylamine N-Acetyltransferases (NATs) to the new “star” allele definitions on PharmVar:

The NAT2 reference allele has now changed: The NG_012246.1 RefSeq differs from X14672.1 (which was used in the past to define star alleles) at the position that corresponds to c.803 (rs1208), where X14672.1 has “A” while NG_012246.1 has “G”. Thus, depending on which reference sequence is utilized, this position is reported as either reference or variant. The transition of allele definitions to the NG_012246.1 RefSeq caused “variant switching”, meaning that all star alleles which were previously described as having c.803A>G lost this variant, as “G” is now considered reference, while all other star alleles gained c.803G>A, as “A” is now considered variant. 


The new reference allele is now catalogued as NAT2*1: The sequence of NG_012246.1 RefSeq corresponds to the allele that was formerly described as NAT2*12A. Its renaming as NAT2*1.001 facilitates the application of PharmVar rules to NAT2 allelic nomenclature, while it also enables the use of NAT2*1 name to describe the reference allele, in line with the star allele nomenclature of other pharmacogenes. To avoid confusion during the transition from the legacy to the new nomenclature, *12 is now retired. Having a NAT2*1 allele grouping in place also facilitates NGS analyses using GRCh38 as a reference.


NAT2*4 is no longer considered as the reference allele: Alleles carrying c.803G>A as their only amino acid changing SNV will be called as *4 according to the new nomenclature. This includes the former NAT2*4 reference allele of sequence X14672.1, now considered a variant and listed as NAT2*4.001. Although this will no longer be used as a reference, it is considered to be functionally equivalent to NAT2*1.001 (formerly NAT2*12A) and may still be used to compare the enzymatic or structural properties of polymorphic NAT2 proteins. 


Star alleles have been renamed: Several NAT2 star alleles have been renamed to conform to PharmVar rules during the transition from the legacy nomenclature to the PharmVar database.


Not all previously defined star alleles have been transferred: In the past, it has not always been clear how a NAT2 haplotype was determined. Many have been inferred via computational phase analysis and were not verified experimentally. In the case of haplotypes where the available evidence from the literature was deemed insufficient to support confident allele definition, those haplotypes were not transferred to PharmVar, but they will remain posted on the original Database of Arylamine N-Acetyltransferases (NATs).


PharmGKB-annotated NAT2 alleles that are not transitioned into PharmVar will remain on PharmGKB with the original Database of Arylamine N-Acetyltransferases (NATs) name (e.g., NAT2*6J). PharmVar-transitioned NAT2 alleles are indicated on PharmGKB NAT2 allele pages with the new "PharmVar Allele" tag (e.g., NAT2*4).


The requirements for new allele definition have changed: In the past, reporting only the SNVs in the NAT2 coding region was sufficient to define new star alleles. According to PharmVar rules, new NAT2 alleles must cover SNVs within defined coordinates that enclose the 5’ untranslated region (including the untranslated first exon), the coding exon, the exon/intron junctions, and the entire 3’ untranslated region relative to genomic reference sequence NG_012246.1. Former alleles covering only the coding region have been annotated with a limited evidence level, as they may have additional variants that were not captured when the allele was first defined.


During the course of updating NAT2 nomenclature, we have been able to confirm several of the former haplotypes, while also identifying new ones. PharmVar encourages submissions of novel haplotypes for star allele definition, as well as for existing definitions to either raise their evidence levels from Limited or Moderate to Definitive, or to solidify their status of Definitive. 

Additional information has been summarized in the Read Me and Change Log documents available on the PharmVar NAT2 page. Also please consult the “NAT2 Look-up” table available under “More Documents” on the same page for an up-to-date record of alleles transferred and a quick reference of PharmVar and legacy star allele names. 

We would like to thank all members of the PharmVar NAT2 Gene Expert Panel for their massive contribution to this project, as well as the NAT Gene Nomenclature Committee for their services to the NAT community since 1998.

Thursday, February 29, 2024

ClinPGx 2024 Registration and Abstract Submission Open



In collaboration with CPIC, PharmGKB, PharmCAT and PharmVar, the Penn Institute for Biomedical Informatics will be hosting the ClinPGx 2024: Knowledge, Implementation, Education meeting on June 20th and 21st, 2024 in Philadelphia, PA. This meeting will provide educational content to cover all aspects of PGx implementation, including knowledgebases, implementation strategy, informatics, use of AI in precision medicine, clinical laboratory insights, and more.

Participants are invited to submit abstracts for the poster sessions. You must be registered for the meeting before your abstract will be accepted.

Please note breakfast & lunch will be provided all conference days.

Registration and detailed agenda


March 22, 2024: Deadline for Abstract Submission. Abstract submission form link here.

April 30, 2024: Deadline for $350 Registration Fee (Starting May 1st, registration fee will be $450)

May 20, 2024: Deadline for Hotel Reservations. Click HERE for hotels offering special rates.

June 1, 2024: Deadline to register for the event.

Thursday, January 25, 2024

Release of Additional PharmGKB Pediatric Drug Summaries

A new round of PharmGKB's pediatric drug summaries is now available on PharmGKB under the Pediatric Focus.

To view the site with the focus active, please select the "Focus" button in the upper right-hand corner and toggle the "Pediatric Focus" setting.

Users can also access the Pediatric Focus on the Focus landing page, or by typing

These pediatric drug summaries contain key information relevant to prenatal, postnatal, and pediatric populations, manually curated from PharmGKB annotations, pathways, CPIC guidelines, and FDA-approved drug labels.

Drugs with newly available summaries include:
PharmGKB continues to add to the list of drugs with pediatric summaries. To browse all drugs with available pediatric summaries, please check out the PharmGKB Pediatric Dashboard.