TNNT3 Gene

Name	troponin T type 3 (skeletal, fast)
Description	The binding of Ca(2+) to the trimeric troponin complex initiates the process of muscle contraction. Increased Ca(2+) concentrations produce a conformational change in the troponin complex that is transmitted to tropomyosin dimers situated along actin filaments. The altered conformation permits increased interaction between a myosin head and an actin filament which, ultimately, produces a muscle contraction. The troponin complex has protein subunits C, I, and T. Subunit C binds Ca(2+) and subunit I binds to actin and inhibits actin-myosin interaction. Subunit T binds the troponin complex to the tropomyosin complex and is also required for Ca(2+)-mediated activation of actomyosin ATPase activity. There are 3 different troponin T genes that encode tissue-specific isoforms of subunit T for fast skeletal-, slow skeletal-, and cardiac-muscle. This gene encodes fast skeletal troponin T protein; also known as troponin T type 3. Alternative splicing results in multiple transcript variants encoding additional distinct troponin T type 3 isoforms. A developmentally regulated switch between fetal/neonatal and adult troponin T type 3 isoforms occurs. Additional splice variants have been described but their biological validity has not been established. Mutations in this gene may cause distal arthrogryposis multiplex congenita type 2B (DA2B). [provided by RefSeq, Oct 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTNNT3 encodes the fast skeletal muscle troponin T, a key regulatory protein that mediates calcium‐dependent interactions among the contractile thin filament proteins required for muscle contraction. In addition to its essential role in striated muscle function, the TNNT3 transcript undergoes extensive alternative splicing during development, generating isoforms that incorporate mutually exclusive exons and additional peptides (for example, an inhibitory f peptide) that modulate its binding to troponin I, troponin C, and tropomyosin to fine‐tune contractile activity. This complex splicing regulation is integral for adapting muscle performance to developmental stages and physiological conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in TNNT3 have been robustly linked to a spectrum of congenital contracture disorders collectively known as distal arthrogryposis. Recurrent missense mutations, such as at residue R63 (with substitutions reported as R63H and R63C), have been identified in patients presenting with clinical features including clubfoot, vertical talus, and digit contractures. These findings underscore the pathogenic consequences of altered TNNT3 function on muscle contractility and limb morphology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAberrant alternative splicing of the TNNT3 gene has also been implicated in the molecular pathology of myotonic dystrophies. In these neuromuscular disorders, mis‐processing of TNNT3 transcripts contributes to an altered balance of its isoforms, which, in turn, may affect muscle fiber composition and functional integrity, thereby playing a role in the muscle weakness and wasting observed in affected individuals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical sarcomeric role, recent studies have revealed that TNNT3 also shuttles to the nucleus in fast skeletal muscle, where it associates with specific DNA motifs implicated in the regulation of p53‐related genes. The decline in TNNT3 expression with aging correlates with reduced excitation–contraction coupling, sarcopenia, and even metabolic dysregulations, highlighting a novel transcriptional regulatory function for TNNT3 in the maintenance of muscle and cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tathagata Chaudhuri, Monalisa Mukherjea, Sanjay Sachdev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of the fetal and alpha/beta exons in the function of fast skeletal troponin T isoforms: correlation with altered Ca2+ regulation associated with development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2005.06.066"}], "href": "https://doi.org/10.1016/j.jmb.2005.06.066"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16081096"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16081096"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Bin Wei, J-P Jin "}, {"type": "b", "children": [{"type": "t", "text": "TNNT1, TNNT2, and TNNT3: Isoform genes, regulation, and structure-function relationships."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2016.01.006"}], "href": "https://doi.org/10.1016/j.gene.2016.01.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26774798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26774798"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Christina A Gurnett, Farhang Alaee, David Desruisseau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Skeletal muscle contractile gene (TNNT3, MYH3, TPM2) mutations not found in vertical talus or clubfoot."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Orthop Relat Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11999-008-0694-5"}], "href": "https://doi.org/10.1007/s11999-008-0694-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19142688"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19142688"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ning Zhao, Miao Jiang, Weitian Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel mutation in TNNT3 associated with Sheldon-Hall syndrome in a Chinese family with vertical talus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Med Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejmg.2011.03.002"}], "href": "https://doi.org/10.1016/j.ejmg.2011.03.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21402185"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21402185"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Anna Alvera Vorster, Peter Beighton, Rajkumar Sewcharan Ramesar "}, {"type": "b", "children": [{"type": "t", "text": "Digitotalar dysmorphism: Molecular elucidation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "S Afr Med J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7196/SAMJ.2016.v106i3.10134"}], "href": "https://doi.org/10.7196/SAMJ.2016.v106i3.10134"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26915936"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26915936"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jinfang Lu, Huanzheng Li, He Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The distal arthrogryposis-linked p.R63C variant promotes the stability and nuclear accumulation of TNNT3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Lab Anal (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcla.24089"}], "href": "https://doi.org/10.1002/jcla.24089"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34766372"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34766372"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sergio Salvatori, Sandra Furlan, Marina Fanin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comparative transcriptional and biochemical studies in muscle of myotonic dystrophies (DM1 and DM2)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurol Sci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10072-009-0048-4"}], "href": "https://doi.org/10.1007/s10072-009-0048-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19326042"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19326042"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Anna Vihola, Linda L Bachinski, Mario Sirito, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differences in aberrant expression and splicing of sarcomeric proteins in the myotonic dystrophies DM1 and DM2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00401-010-0637-6"}], "href": "https://doi.org/10.1007/s00401-010-0637-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20066428"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20066428"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yury O Nunez Lopez, Maria Laura Messi, Richard E Pratley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Troponin T3 associates with DNA consensus sequence that overlaps with p53 binding motifs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Gerontol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.exger.2018.03.012"}], "href": "https://doi.org/10.1016/j.exger.2018.03.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29596868"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29596868"}]}]}]}
Synonyms	TNTF, beta-TnTF
Proteins	TNNT3_HUMAN
NCBI Gene ID	7140
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TNNT3 has 4,428 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 119 datasets.

Click the + buttons to view associations for TNNT3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TNNT3 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of TNNT3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of TNNT3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of TNNT3 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of TNNT3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of TNNT3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of TNNT3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of TNNT3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of TNNT3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of TNNT3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of TNNT3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of TNNT3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with TNNT3 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of TNNT3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TNNT3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of TNNT3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with TNNT3 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of TNNT3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TNNT3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing TNNT3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with TNNT3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with TNNT3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TNNT3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with TNNT3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with TNNT3 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by TNNT3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving TNNT3 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with TNNT3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with TNNT3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with TNNT3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with TNNT3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with TNNT3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TNNT3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at TNNT3 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of TNNT3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TNNT3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing TNNT3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with TNNT3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with TNNT3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of TNNT3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with TNNT3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.