This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1002/humu.23712. This article is protected by copyright. All rights reserved. Phenylalanine hydroxylase variants interact with the co-chaperone DNAJC12 Kunwar Jung-KC 1 , Nastassja Himmelreich 2 , Karina S. Prestegård 1 , Tie-Jun Sten Shi 1 , Tanja Scherer 3 , Ming Ying 1 , Ana Jorge-Finnigan 1 , Beat Thöny 3 , Nenad Blau 2,3* , and Aurora Martinez 1* 1 Department of Biomedicine, University of Bergen, Bergen, Norway 2 Dietmar-Hopp-Metabolic Center, University Children's Hospital, Heidelberg, Germany. 3 Division of Metabolism, University Children's Hospital Zürich, Zürich, Switzerland. Jung-KC K and Nastassja Himmelreich have contributed equally to this work *Correspondence to Aurora Martinez, aurora.martinez@uib.no and Nenad Blau, Nenad.Blau@med.uni-heidelberg.de Funding: This work was supported by Research Council of Norway grants FRIMEDBIO 261826/F20 and FORNY 248889/O30, the K.G. Jebsen Centre for Neuropsychiatric Disorders, and the Western Norway Regional Health Authorities (Helse-Vest project 370218) (to A.M.), and by the FP7-HEALTH-2012- INNOVATION-1 EU Grant No. 305444 (to NB). Key words: HSP40 co-chaperones, molecular chaperones, protein misfolding, protein aggregation, hyperphenylalanine Abstract DNAJC12, a type III member of the HSP40/DNAJ family, has been identified as the specific co-chaperone of phenylalanine hydroxylase (PAH) and the other aromatic amino acid hydroxylases. DNAJ proteins work together with molecular chaperones of the HSP70-family to assist in proper folding and maintenance of intracellular stability of their clients. Autosomal recessive mutations in DNAJC12 were found to reduce PAH levels, leading to hyperphenylalaninemia (HPA) in patients without mutations in PAH. In this work we investigated the interaction of normal wild-type DNAJC12 with mutant PAH in cells