Troponin I (TnI), along with troponin T (TnT) and troponin C (TnC), is one of 3 subunits that form the troponin complex of the thin filaments of striated muscle. TnI is the inhibitory subunit; blocking actin-myosin interactions and thereby mediating striated muscle relaxation. The TnI subfamily contains three genes: TnI-skeletal-fast-twitch, TnI-skeletal-slow-twitch, and TnI-ca... See more...

Aliases for TNNI3 Gene

Aliases for TNNI3 Gene

  • Troponin I3, Cardiac Type 2 3 5
  • Cardiomyopathy, Dilated 2A (Autosomal Recessive) 2 3
  • Troponin I Type 3 (Cardiac) 2 3
  • Troponin I, Cardiac Muscle 3 4
  • TNNC1 3 4
  • Cardiac Troponin I 4
  • Troponin I Type 3 2
  • CMD1FF 3
  • CMD2A 3
  • CMH7 3
  • RCM1 3
  • CTnI 3

External Ids for TNNI3 Gene

Previous HGNC Symbols for TNNI3 Gene

  • CMD2A

Previous GeneCards Identifiers for TNNI3 Gene

  • GC19M056535
  • GC19M056094
  • GC19M060340
  • GC19M060354
  • GC19M055663
  • GC19M051986

Summaries for TNNI3 Gene

Entrez Gene Summary for TNNI3 Gene

  • Troponin I (TnI), along with troponin T (TnT) and troponin C (TnC), is one of 3 subunits that form the troponin complex of the thin filaments of striated muscle. TnI is the inhibitory subunit; blocking actin-myosin interactions and thereby mediating striated muscle relaxation. The TnI subfamily contains three genes: TnI-skeletal-fast-twitch, TnI-skeletal-slow-twitch, and TnI-cardiac. This gene encodes the TnI-cardiac protein and is exclusively expressed in cardiac muscle tissues. Mutations in this gene cause familial hypertrophic cardiomyopathy type 7 (CMH7) and familial restrictive cardiomyopathy (RCM). [provided by RefSeq, Jul 2008]

GeneCards Summary for TNNI3 Gene

TNNI3 (Troponin I3, Cardiac Type) is a Protein Coding gene. Diseases associated with TNNI3 include Cardiomyopathy, Dilated, 2A and Cardiomyopathy, Familial Hypertrophic, 7. Among its related pathways are Cardiac conduction and Dilated cardiomyopathy (DCM). Gene Ontology (GO) annotations related to this gene include protein kinase binding and protein domain specific binding. An important paralog of this gene is TNNI1.

UniProtKB/Swiss-Prot Summary for TNNI3 Gene

  • Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.

Gene Wiki entry for TNNI3 Gene

Additional gene information for TNNI3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TNNI3 Gene

Genomics for TNNI3 Gene

GeneHancer (GH) Regulatory Elements for TNNI3 Gene

Promoters and enhancers for TNNI3 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TNNI3 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TNNI3

Top Transcription factor binding sites by QIAGEN in the TNNI3 gene promoter:
  • AP-4
  • CUTL1
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • E2F-5
  • GATA-1
  • GATA-2

Genomic Locations for TNNI3 Gene

Genomic Locations for TNNI3 Gene
chr19:55,151,767-55,157,773
(GRCh38/hg38)
Size:
6,007 bases
Orientation:
Minus strand
chr19:55,663,135-55,669,141
(GRCh37/hg19)
Size:
6,007 bases
Orientation:
Minus strand

Genomic View for TNNI3 Gene

Genes around TNNI3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TNNI3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TNNI3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TNNI3 Gene

Proteins for TNNI3 Gene

  • Protein details for TNNI3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P19429-TNNI3_HUMAN
    Recommended name:
    Troponin I, cardiac muscle
    Protein Accession:
    P19429

    Protein attributes for TNNI3 Gene

    Size:
    210 amino acids
    Molecular mass:
    24008 Da
    Quaternary structure:
    • Binds to actin and tropomyosin. Interacts with TRIM63. Interacts with STK4/MST1.

    Three dimensional structures from OCA and Proteopedia for TNNI3 Gene

neXtProt entry for TNNI3 Gene

Post-translational modifications for TNNI3 Gene

  • Phosphorylated at Ser-42 and Ser-44 by PRKCE; phosphorylation increases myocardium contractile dysfunction (By similarity). Phosphorylated at Ser-23 and Ser-24 by PRKD1; phosphorylation reduces myofilament calcium sensitivity. Phosphorylated preferentially at Thr-31. Phosphorylation by STK4/MST1 alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for TNNI3 Gene

Antibody Products

No data available for DME Specific Peptides for TNNI3 Gene

Domains & Families for TNNI3 Gene

Gene Families for TNNI3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Candidate cardiovascular disease genes
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for TNNI3 Gene

Blocks:
  • Troponin
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for TNNI3 Gene

GenScript: Design optimal peptide antigens:
  • Troponin I type 3 cardiac (A8CLQ8_HUMAN)
  • Cardiac troponin I (A8CLR6_HUMAN)
  • Cardiac troponin I (A8CLS6_HUMAN)
  • Troponin I type 3 cardiac (A8CN18_HUMAN)
  • Cardiac troponin I (A9UD06_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P19429

UniProtKB/Swiss-Prot:

TNNI3_HUMAN :
  • Belongs to the troponin I family.
Family:
  • Belongs to the troponin I family.
genes like me logo Genes that share domains with TNNI3: view

Function for TNNI3 Gene

Molecular function for TNNI3 Gene

UniProtKB/Swiss-Prot Function:
Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
GENATLAS Biochemistry:
troponin I3,inhibitory subunit,component of the troponin complex forming the calcium-sensitive molecular switch that regulates striated muscle contraction in response to modifications in intracellular concentration cardiac muscle,organized in pair with TNNT1

Gene Ontology (GO) - Molecular Function for TNNI3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003779 actin binding IDA,IEA 10806205
GO:0005515 protein binding IPI 10806205
GO:0019855 calcium channel inhibitor activity IPI 12809519
GO:0019901 protein kinase binding IPI 12721663
GO:0019904 protein domain specific binding IPI 11984006
genes like me logo Genes that share ontologies with TNNI3: view
genes like me logo Genes that share phenotypes with TNNI3: view

Human Phenotype Ontology for TNNI3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TNNI3 Gene

MGI Knock Outs for TNNI3:

Animal Model Products

CRISPR Products

miRNA for TNNI3 Gene

miRTarBase miRNAs that target TNNI3

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TNNI3

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Transcription Factor Targets and HOMER Transcription for TNNI3 Gene

Localization for TNNI3 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TNNI3 gene
Compartment Confidence
cytoskeleton 5
nucleus 4
cytosol 4
plasma membrane 2
extracellular 2
mitochondrion 2
endoplasmic reticulum 2
endosome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for TNNI3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005623 cell IEA --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0005861 troponin complex IEA,IDA 7957210
GO:0030016 myofibril IEA --
genes like me logo Genes that share ontologies with TNNI3: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for TNNI3 Gene

Pathways & Interactions for TNNI3 Gene

PathCards logo

SuperPathways for TNNI3 Gene

genes like me logo Genes that share pathways with TNNI3: view

Pathways by source for TNNI3 Gene

2 GeneGo (Thomson Reuters) pathways for TNNI3 Gene
  • Development Beta-adrenergic receptors signaling via cAMP
  • Signal transduction_PKA signaling
4 Qiagen pathways for TNNI3 Gene
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • cAMP Pathway
  • PKA Signaling
2 Cell Signaling Technology pathways for TNNI3 Gene

SIGNOR curated interactions for TNNI3 Gene

Is activated by:
Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for TNNI3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001570 vasculogenesis ISS --
GO:0001980 regulation of systemic arterial blood pressure by ischemic conditions ISS,IEA --
GO:0003009 skeletal muscle contraction IBA 21873635
GO:0006874 cellular calcium ion homeostasis IEA,ISS --
GO:0006936 muscle contraction IBA 21873635
genes like me logo Genes that share ontologies with TNNI3: view

Drugs & Compounds for TNNI3 Gene

(4) Drugs for TNNI3 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Calcium Approved Nutra 7884
n-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide Experimental Pharma Target 0

(1) Additional Compounds for TNNI3 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TNNI3: view

Transcripts for TNNI3 Gene

mRNA/cDNA for TNNI3 Gene

1 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TNNI3

Alternative Splicing Database (ASD) splice patterns (SP) for TNNI3 Gene

ExUns: 1 ^ 2a · 2b · 2c ^ 3a · 3b · 3c · 3d ^ 4 ^ 5a · 5b ^ 6a · 6b
SP1: - - - -
SP2: - -
SP3:
SP4: -

Relevant External Links for TNNI3 Gene

GeneLoc Exon Structure for
TNNI3

Expression for TNNI3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TNNI3 Gene

mRNA differential expression in normal tissues according to GTEx for TNNI3 Gene

This gene is overexpressed in Heart - Left Ventricle (x38.8) and Heart - Atrial Appendage (x13.2).

Protein differential expression in normal tissues from HIPED for TNNI3 Gene

This gene is overexpressed in Heart (64.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for TNNI3 Gene



Protein tissue co-expression partners for TNNI3 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TNNI3

SOURCE GeneReport for Unigene cluster for TNNI3 Gene:

Hs.709179

Evidence on tissue expression from TISSUES for TNNI3 Gene

  • Heart(4.9)
  • Muscle(4.9)
  • Blood(3.1)
  • Nervous system(2.5)

Phenotype-based relationships between genes and organs from Gene ORGANizer for TNNI3 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • nervous
  • respiratory
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • ear
  • head
Thorax:
  • heart
  • heart valve
  • lung
Limb:
  • lower limb
  • upper limb
General:
  • blood
  • blood vessel
  • coagulation system
  • red blood cell
  • spinal cord
genes like me logo Genes that share expression patterns with TNNI3: view

No data available for mRNA Expression by UniProt/SwissProt for TNNI3 Gene

Orthologs for TNNI3 Gene

This gene was present in the common ancestor of animals.

Orthologs for TNNI3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TNNI3 31 30
  • 99.63 (n)
OneToOne
cow
(Bos Taurus)
Mammalia TNNI3 31
  • 92 (a)
OneToOne
LOC511094 30
  • 88.57 (n)
dog
(Canis familiaris)
Mammalia TNNI3 31 30
  • 90.95 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Tnni3 17 31 30
  • 88.89 (n)
rat
(Rattus norvegicus)
Mammalia Tnni3 30
  • 87.72 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 85 (a)
OneToMany
-- 31
  • 65 (a)
OneToMany
oppossum
(Monodelphis domestica)
Mammalia TNNI3 31
  • 67 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TNNI3 31
  • 62 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia tnni3 30
  • 71.52 (n)
zebrafish
(Danio rerio)
Actinopterygii tnni1al 31
  • 58 (a)
ManyToMany
tnni1c 31
  • 57 (a)
ManyToMany
zgc:112242 31
  • 56 (a)
ManyToMany
zgc:101560 31 31
  • 51 (a)
ManyToMany
si:dkey-206m15.8 31
  • 49 (a)
ManyToMany
fruit fly
(Drosophila melanogaster)
Insecta CG17669 32
  • 30 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.11013 31
  • 45 (a)
OneToMany
Species where no ortholog for TNNI3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for TNNI3 Gene

ENSEMBL:
Gene Tree for TNNI3 (if available)
TreeFam:
Gene Tree for TNNI3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TNNI3: view image

Paralogs for TNNI3 Gene

Paralogs for TNNI3 Gene

(2) SIMAP similar genes for TNNI3 Gene using alignment to 12 proteins:

  • TNNI3_HUMAN
  • A8CLQ8_HUMAN
  • A8CLR6_HUMAN
  • A8CLS6_HUMAN
  • A8CN18_HUMAN
  • A9UD06_HUMAN
  • B6D427_HUMAN
  • K7EJP0_HUMAN
  • K7EN02_HUMAN
  • Q2PT48_HUMAN
  • Q6FGU5_HUMAN
  • Q6FGX2_HUMAN
genes like me logo Genes that share paralogs with TNNI3: view

Variants for TNNI3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TNNI3 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
636350 Uncertain Significance: not provided 55,156,207(-) C/T SYNONYMOUS_VARIANT
636484 Uncertain Significance: not provided 55,154,743(-) C/T MISSENSE_VARIANT
636539 Uncertain Significance: not provided 55,156,259(-) G/A MISSENSE_VARIANT
636901 Uncertain Significance: not provided 55,154,184(-) ATCT/A INFRAME_DELETION
636992 Conflicting Interpretations: Familial restrictive cardiomyopathy; not provided 55,151,842(-) C/CA NONSENSE

Additional dbSNP identifiers (rs#s) for TNNI3 Gene

Structural Variations from Database of Genomic Variants (DGV) for TNNI3 Gene

Variant ID Type Subtype PubMed ID
dgv1820n106 CNV insertion 24896259
esv1785452 CNV insertion 17803354
esv2485681 CNV deletion 19546169
nsv1111177 CNV tandem duplication 24896259
nsv1147761 CNV insertion 26484159

Variation tolerance for TNNI3 Gene

Residual Variation Intolerance Score: 61.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.06; 21.60% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TNNI3 Gene

Human Gene Mutation Database (HGMD)
TNNI3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TNNI3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TNNI3 Gene

Disorders for TNNI3 Gene

MalaCards: The human disease database

(82) MalaCards diseases for TNNI3 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search TNNI3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TNNI3_HUMAN
  • Cardiomyopathy, familial hypertrophic 7 (CMH7) [MIM:613690]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269 PubMed:11815426, ECO:0000269 PubMed:12707239, ECO:0000269 PubMed:12974739, ECO:0000269 PubMed:16199542, ECO:0000269 PubMed:9241277}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Cardiomyopathy, familial restrictive 1 (RCM1) [MIM:115210]: A heart disorder characterized by impaired filling of the ventricles with reduced diastolic volume, in the presence of normal or near normal wall thickness and systolic function. {ECO:0000269 PubMed:12531876}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Cardiomyopathy, dilated 2A (CMD2A) [MIM:611880]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269 PubMed:15070570}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Cardiomyopathy, dilated 1FF (CMD1FF) [MIM:613286]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269 PubMed:19590045, ECO:0000269 PubMed:21846512}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for TNNI3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with TNNI3: view

No data available for Genatlas for TNNI3 Gene

Publications for TNNI3 Gene

  1. Compound and double mutations in patients with hypertrophic cardiomyopathy: implications for genetic testing and counselling. (PMID: 16199542) Ingles J … Semsarian C (Journal of medical genetics 2005) 3 4 23 41 54
  2. Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy. (PMID: 9241277) Kimura A … Sasazuki T (Nature genetics 1997) 2 3 4 23 54
  3. Coding sequence rare variants identified in MYBPC3, MYH6, TPM1, TNNC1, and TNNI3 from 312 patients with familial or idiopathic dilated cardiomyopathy. (PMID: 20215591) Hershberger RE … Gonzalez-Quintana J (Circulation. Cardiovascular genetics 2010) 3 23 41 54
  4. Prevalence of sarcomere protein gene mutations in preadolescent children with hypertrophic cardiomyopathy. (PMID: 20031618) Kaski JP … Elliott PM (Circulation. Cardiovascular genetics 2009) 3 23 41 54
  5. The role of sarcomere gene mutations in patients with idiopathic dilated cardiomyopathy. (PMID: 19293840) Møller DV … Køber L (European journal of human genetics : EJHG 2009) 3 23 41 54

Products for TNNI3 Gene