ACKR1 /Duffy‐null genotype testing for clozapine: A guideline developed by the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI‐PGx)

@article{murtough2026ackr1,
  title = {{ACKR1 /Duffy‐null genotype testing for clozapine: A guideline developed by the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI‐PGx)}},
  author = {Stephen Murtough and Oriella Stellakis and Daisy Mills and Blanca Bjourson and Vicky Chaplin and Dharmisha Chauhan and Beverley Chipp and Marius Cotic and Jana de Villiers and Olubanké Dzahini and Frances Elmslie and Katie Evans and Shreyans Gandhi and D. O. HUGHES and Huajie Jin and Daniele Panconesi and Anna Skowrońska and Sanjay M. Sisodiya and Ed Silva and Vicky Stinton and Sara Stuart‐Smith and Sarah Tarrant and David M. Taylor and Lauren Varney and James TR Walters and Michelle Wood and Jessica Woodley and Cinzia Dello Russo and Munir Pirmohamed and Elvira Bramon},
  journal = {British Journal of Clinical Pharmacology},
  year = {2026},
  month = may,
  doi = {10.1002/bcp.70576},
  url = {https://doi.org/10.1002/bcp.70576},
  note = {CC BY},
}

TY  - JOUR
TI  - ACKR1 /Duffy‐null genotype testing for clozapine: A guideline developed by the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI‐PGx)
AU  - Stephen Murtough
AU  - Oriella Stellakis
AU  - Daisy Mills
AU  - Blanca Bjourson
AU  - Vicky Chaplin
AU  - Dharmisha Chauhan
AU  - Beverley Chipp
AU  - Marius Cotic
AU  - Jana de Villiers
AU  - Olubanké Dzahini
AU  - Frances Elmslie
AU  - Katie Evans
AU  - Shreyans Gandhi
AU  - D. O. HUGHES
AU  - Huajie Jin
AU  - Daniele Panconesi
AU  - Anna Skowrońska
AU  - Sanjay M. Sisodiya
AU  - Ed Silva
AU  - Vicky Stinton
AU  - Sara Stuart‐Smith
AU  - Sarah Tarrant
AU  - David M. Taylor
AU  - Lauren Varney
AU  - James TR Walters
AU  - Michelle Wood
AU  - Jessica Woodley
AU  - Cinzia Dello Russo
AU  - Munir Pirmohamed
AU  - Elvira Bramon
PY  - 2026
DA  - 2026/05/13
JO  - British Journal of Clinical Pharmacology
DO  - 10.1002/bcp.70576
UR  - https://doi.org/10.1002/bcp.70576
AB  - Clozapine is licenced for treatment‐resistant schizophrenia and psychosis in Parkinson's disease. In the United Kingdom, there is a mandatory requirement for absolute neutrophil count (ANC) and white blood cell count (WBC) monitoring to safeguard against agranulocytosis. Some people have naturally low ANCs without increased infection risk, caused by a homozygous T > C variant in ACKR1 , commonly called the Duffy‐null genotype. This condition is known as ADAN ( ACKR1 / DARC ‐associated neutropenia) and synonyms include DANC (Duffy‐null associated neutrophil count) and BEN (benign ethnic neutropenia). It is usual UK practice to lower WBC/ANC thresholds for people confirmed to have ADAN. However, ADAN often remains undetected, resulting in unnecessary discontinuation and exclusion from clozapine. This CERSI‐PGx guideline provides a framework to offer ACKR1 genotype testing within the existing clinical pathway. We recommend three eligibility criteria, including pre‐emptive testing for all people starting clozapine, testing for people registered in the Central Non‐Rechallenge Database and reactive testing following a below‐threshold blood result (defined as ‘amber’ or ‘red’). We recommend that people with the Duffy‐null genotype should be monitored using revised WBC/ANC thresholds for ADAN. Regardless of ACKR1 genotype, haematology input is required for people returning a WBC < 2.0 × 10 9 /L and/or ANC < 1.0 × 10 9 /L who present with a key clinical feature, such as sustained temperature ≥38°C. Finally, we summarize health economic evidence, estimating in the first year of testing, 129 people with the Duffy‐null genotype could be identified, resulting in savings ranging from £42 732 to £727 990. We propose ACKR1 testing as a cost‐effective approach for facilitating access to clozapine, the optimal therapy for treatment‐resistant schizophrenia.
SN  - 0306-5251
SN  - 1365-2125
ER  -