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Article History

Received: 11 October 2024

Accepted: 3 January 2025

First Online: 10 March 2025

Acknowledgements

: The authors thank the following for their helpful conversations regarding the design of guides for genome editing, interpretation and explanation of results and acquisition of samples for data analysis: B. Koller (Genetics, UNC Chapel Hill, USA); A. Crain (BBSP, UNC Chapel Hill, USA); L. Bonnycastle (Center for Precision Health Research, NHGRI, USA); A. Swift (Center for Precision Health Research, NHGRI, USA); N. Tucker (Masonic Research Institute, USA); A. Iyengar (Genetics, UNC Chapel Hill, USA); the staff of the Michael Hooker Proteomics Core (Lineberger Comprehensive Cancer Center, UNC Chapel Hill, USA), including N. Barker-Krantz, A. Mordant and T. Webb; and J. Dow and A. Hedgecock of the UNC Flow Cytometry Core (Lineberger Comprehensive Cancer Center, UNC Chapel Hill, USA). V. Chirasani of the R. L. Juliano Structural Bioinformatics Core performed the structural modelling of TBC1D30 proteins and potential interactors (Lineberger Comprehensive Cancer Center, UNC Chapel Hill, USA). Human pancreatic islets were provided by the National Disease Research Interchange and the NIDDK-funded Integrated Islet Distribution Program (IIDP) (RRID:SCR _014387) at City of Hope. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health and by NCI, NHGRI, NHLBI, NIDA, NIMH and NINDS. The data used for the analyses described in this manuscript were obtained from the GTEx Portal in May 2023.

: DNA sequences of islet TBC1D30 isoforms are available at GenBank via accession codes PQ349258 and PQ349259. Proteomics data are available at ProteomExchange via accession code PXD047652.

: The authors acknowledge support from National Institutes of Health (NIH) grants T32GM135128, T32HL129982, R01DK072193 and UM1DK126185. DNL is supported by the American Diabetes Association (1-19-JDF-081) and NIH grant P30AR069619. KMV is supported by NIH grants P30AR069619 and F31DK132982. This research includes work conducted using the UNC Proteomics Core Facility, which is supported in part by the NCI Center Core Support Grant (2P30CA016086-45) to the UNC Lineberger Comprehensive Cancer Center. Bioinformatic modelling was done by the R. L. Juliano Structural Bioinformatics Core and is supported in part by grant P30CA016086 to the UNC Lineberger Comprehensive Cancer Center. The Integrated Islet Distrubution Program is funded by NIH Grant # U24DK098085.

: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

: VAP and KLM designed the study. VAP, SV, KMV, AER, AHM, MEC and CAM acquired data. VAP, SV, KMV, JDR, CAM, LEH, KAB and DNL performed analyses. VAP drafted the manuscript, and all authors interpreted results and reviewed and approved the manuscript. KLM supervised all aspects of the study and is the guarantor of this work and, as such, takes responsibility for the integrity of the data and the accuracy of the data analysis.