Abstract
In the two decades since the discovery of TNNI3K it has been implicated in multiple cardiac phenotypes and physiological processes. TNNI3K is an understudied kinase, which is mainly expressed in the heart. Human genetic variants in TNNI3K are associated with supraventricular arrhythmias, conduction disease, and cardiomyopathy. Furthermore, studies in mice implicate the gene in cardiac hypertrophy, cardiac regeneration, and recovery after ischemia/reperfusion injury. Several new papers on TNNI3K have been published since the last overview, broadening the clinical perspective of TNNI3K variants and our understanding of the underlying molecular biology. We here provide an overview of the role of TNNI3K in cardiomyopathy and arrhythmia covering both a clinical perspective and basic science advancements. In addition, we review the potential of TNNI3K as a target for clinical treatments in different cardiac diseases.
Highlights
Sci. 2021, 22, 6422. https://doi.org/Troponin I interacting kinase (TNNI3K), encoded by TNNI3K, was discovered byZhao et al in 2003 [1]
BLAST analysis showed high similarity to the integrinlinked kinase (ILK), which is involved in cardiac growth, contractility, and repair
Considering multiple mechanisms are involved in cardiac conduction, we suggest that Tnni3k could affect gap-junctional coupling or CM
Summary
Distribution of TNNI3K variants associated with cardiac diseases and with serine-rich domain. This protein is absent from theprotein large dataset of amino the genotype in kDa) humans, potentially resulting in a fusion of 949 acidsexpression (approximately (GTEx) and no evidence of this read-through gene the has been reported. Sites reduced the transcriptional activity of Tnni3k, pointing to this transcription factor as a Several downstream targets for TNNI3K have been proposed, but the majority of critical regulator of Tnni3k expression in mice [8]. 2007, the antioxidant described possible interactor, that none of the these targets have beenof validated in animal models and many new possible which binds ankyrin domain and downregulates its kinase activity [5]. P38 and PKA as downstream targets of Tnni3k but it is unknown whether there is a direct interaction in vitro or in vivo [2,11]. It is important to highlight that none of these targets have been validated in animal models and many new possible targets remain to be identified
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
