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    TNNI3K TNNI3 interacting kinase [ Homo sapiens (human) ]

    Gene ID: 51086, updated on 2-Nov-2024

    Summary

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    Official Symbol
    TNNI3Kprovided by HGNC
    Official Full Name
    TNNI3 interacting kinaseprovided by HGNC
    Primary source
    HGNC:HGNC:19661
    See related
    Ensembl:ENSG00000116783 MIM:613932; AllianceGenome:HGNC:19661
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CARK; CCDD
    Summary
    This gene encodes a protein that belongs to the MAP kinase kinase kinase (MAPKKK) family of protein kinases. The protein contains ankyrin repeat, protein kinase and serine-rich domains and is thought to play a role in cardiac physiology. [provided by RefSeq, Sep 2012]
    Expression
    Biased expression in heart (RPKM 19.3), testis (RPKM 1.3) and 1 other tissue See more
    Orthologs
    mouse all
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    Genomic context

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    See TNNI3K in Genome Data Viewer
    Location:
    1p31.1
    Exon count:
    25
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (74235387..74544428)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (74076908..74385812)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (74701071..75010112)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene leucine rich repeats and IQ motif containing 3 Neighboring gene MPRA-validated peak287 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 994 Neighboring gene FPGT-TNNI3K readthrough Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr1:74710898-74711549 Neighboring gene fucose-1-phosphate guanylyltransferase Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:74817906-74818406 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:74818407-74818907 Neighboring gene Sharpr-MPRA regulatory region 9784 Neighboring gene leucine rich repeat containing 53 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr1:74994213-74994947 Neighboring gene ERICH3 antisense RNA 1 Neighboring gene glutamate rich 3 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr1:75187729-75188286 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1199 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:75198416-75199126 Neighboring gene crystallin zeta

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Ventricular septal defect and restrictive cardiomyopathy in a paediatric TNNI3 mutation carrier. Yang SW, et al. Cardiol Young, 2010 Oct. PMID 20569525
    2. Reduced kinase function in two ultra-rare TNNI3K variants in families with congenital junctional ectopic tachycardia. Pham C, et al. Clin Genet, 2024 Jul. PMID 38424693
    3. Whole exome sequencing identifies the TNNI3K gene as a cause of familial conduction system disease and congenital junctional ectopic tachycardia. Xi Y, et al. Int J Cardiol, 2015 Apr 15. PMID 25791106, Free PMC Article
    4. Overexpression of Cardiac-Specific Kinase TNNI3K Promotes Mouse Embryonic Stem Cells Differentiation into Cardiomyocytes. Wang Y, et al. Cell Physiol Biochem, 2017. PMID 28135716
    5. Adenovirus-mediated overexpression of cardiac troponin I-interacting kinase promotes cardiomyocyte hypertrophy. Wang L, et al. Clin Exp Pharmacol Physiol, 2011 Apr. PMID 21314842

    See all (43) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Reduced kinase function in two ultra-rare TNNI3K variants in families with congenital junctional ectopic tachycardia.
      Title: Reduced kinase function in two ultra-rare TNNI3K variants in families with congenital junctional ectopic tachycardia.
    2. A Novel Missense Mutation in TNNI3K Causes Recessively Inherited Cardiac Conduction Disease in a Consanguineous Pakistani Family.
      Title: A Novel Missense Mutation in TNNI3K Causes Recessively Inherited Cardiac Conduction Disease in a Consanguineous Pakistani Family.
    3. A SPRY1 domain cardiac ryanodine receptor variant associated with short-coupled torsade de pointes.
      Title: A SPRY1 domain cardiac ryanodine receptor variant associated with short-coupled torsade de pointes.
    4. Identification of a nonsense mutation in TNNI3K associated with cardiac conduction disease.
      Title: Identification of a nonsense mutation in TNNI3K associated with cardiac conduction disease.
    5. New Insights into 4-Anilinoquinazolines as Inhibitors of Cardiac Troponin I-Interacting Kinase (TNNi3K).
      Title: New Insights into 4-Anilinoquinazolines as Inhibitors of Cardiac Troponin I-Interacting Kinase (TNNi3K).
    6. A heterozygous p.Thr539Ala mutation in TNNI3K, a cardiac-specific kinase, is the likely cause for a novel familial cardiac conduction disease (FCCD)
      Title: Whole exome sequencing identifies the TNNI3K gene as a cause of familial conduction system disease and congenital junctional ectopic tachycardia.
    7. we show that several common human TNNI3K kinase domain variants substantially compromise kinase activity, suggesting that TNNI3K may influence human heart regenerative capacity and potentially also other aspects of human heart disease.
      Title: Tnni3k alleles influence ventricular mononuclear diploid cardiomyocyte frequency.
    8. Results showed that TNNI3K was highly in cholangiocarcinoma (CCA) patients. Furthermore, TNNI3K-knockdown decreased the growth of CCA cell lines.
      Title: Over-expression of TNNI3K is associated with early-stage carcinogenesis of cholangiocarcinoma.
    9. results suggest that ACE2, TNNI3K and CALM3 polymorphisms are associated with increased risk of hypertrophic cardiomyopathies and dilated cardiomyopathies and may act as disease modifiers of these diseases.
      Title: ACE2, CALM3 and TNNI3K polymorphisms as potential disease modifiers in hypertrophic and dilated cardiomyopathies.
    10. A splice site mutation of TNNI3 Interacting Kinase (TNNI3K) was identified and co-segregated with the dilated cardiomyopathy (DCM) and cardiac conduction disease (CCD) affected family members.
      Title: Whole exome sequencing identifies a novel mutation (c.333 + 2T > C) of TNNI3K in a Chinese family with dilated cardiomyopathy and cardiac conduction disease.
    Submit: New GeneRIF Correction See all GeneRIFs (24)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Atrial conduction disease
    MedGen: C4015285 OMIM: 616117 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.
    EBI GWAS Catalog
    Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course.
    EBI GWAS Catalog
    Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity.
    EBI GWAS Catalog
    Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.
    EBI GWAS Catalog
    Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Readthrough FPGT-TNNI3K

    Readthrough gene: FPGT-TNNI3K, Included gene: FPGT

    Homology

    Clone Names

    • MGC33828, MGC142099

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AS1 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in bundle of His cell to Purkinje myocyte communication IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of cardiac conduction IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in regulation of cardiac muscle contraction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of heart rate IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in regulation of heart rate IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    serine/threonine-protein kinase TNNI3K
    Names
    cardiac ankyrin repeat kinase
    cardiac troponin I-interacting kinase
    NP_057062.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_032939.2 RefSeqGene

      Range
      42135..351176
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_678

    mRNA and Protein(s)

    1. NM_015978.3 → NP_057062.1  serine/threonine-protein kinase TNNI3K

      See identical proteins and their annotated locations for NP_057062.1

      Status: REVIEWED

      Source sequence(s)
      AA758546, BC113539, BX502807
      Consensus CDS
      CCDS664.1
      UniProtKB/Swiss-Prot
      Q17RN0, Q49AR1, Q59H18, Q6MZS9, Q9Y2V6
      UniProtKB/TrEMBL
      V9GXZ4
      Related
      ENSP00000322251.3, ENST00000326637.8
      Conserved Domains (3) summary
      cd00204
      Location:99 → 220
      ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
      cd14064
      Location:469 → 722
      PKc_TNNI3K; Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase
      sd00045
      Location:134 → 164
      ANK; ANK repeat [structural motif]

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      74235387..74544428
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      74076908..74385812
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q59H18.3 GenPept UniProtKB/Swiss-Prot:Q59H18

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
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