TNNI3 (troponin I3, cardiac type)

Gene

• Entrez ID: 7137
• Gene name: Troponin I3, cardiac type
• Gene symbol: TNNI3
• Synonyms: CMD1FF, CMD2A, CMH7, RCM1, TNNC1, cTnI
• Chromosome: 19
• Chromosome location: 19q13.42
• Summary: 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). Troponin I is useful in making a diagnosis of heart failure, and of ischemic heart disease. An elevated level of troponin is also now used as indicator of acute myocardial injury in patients hospitalized with moderate/severe Coronavirus Disease 2019 (COVID-19). Such elevation has also been associated with higher risk of mortality in cardiovascular disease patients hospitalized due to COVID-19. [provided by RefSeq, Aug 2020]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs7252610	C>A,G,T	Likely-benign, conflicting-interpretations-of-pathogenicity, benign, benign-likely-benign	Intron variant
rs77615401	G>A	Benign-likely-benign, likely-benign, risk-factor, benign	Coding sequence variant, missense variant
rs104894724	G>A,C	Pathogenic	Coding sequence variant, missense variant
rs104894725	T>C,G	Pathogenic	Coding sequence variant, missense variant
rs104894727	C>A,T	Likely-pathogenic, pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs104894728	T>C	Pathogenic	Coding sequence variant, missense variant
rs104894729	C>A,G,T	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs104894730	T>C	Pathogenic	Coding sequence variant, missense variant
rs121917760	A>G,T	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs121917761	C>T	Pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs193922409	C>A,T	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs267607127	C>T	Pathogenic	Missense variant, coding sequence variant
rs267607128	G>A,T	Pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs267607129	G>C	Pathogenic	Missense variant, coding sequence variant
rs267607130	T>G	Pathogenic	Missense variant, coding sequence variant
rs368861241	G>A	Pathogenic, likely-pathogenic, pathogenic-likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs377258542	G>C,T	Conflicting-interpretations-of-pathogenicity	Intron variant
rs397516340	C>A	Likely-pathogenic	Splice acceptor variant
rs397516347	C>T	Pathogenic-likely-pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs397516348	G>T	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs397516349	C>T	Pathogenic-likely-pathogenic, likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs397516351	TTC>-	Pathogenic	Inframe deletion, coding sequence variant
rs397516352	A>G	Likely-pathogenic	Coding sequence variant, missense variant
rs397516353	G>A	Pathogenic	Coding sequence variant, missense variant
rs397516354	C>A,G,T	Pathogenic-likely-pathogenic, likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs397516355	C>A,T	Likely-pathogenic, pathogenic	Stop gained, coding sequence variant, missense variant
rs397516356	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs397516357	C>T	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs397516358	C>A,G	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs727503499	G>A	Pathogenic	Coding sequence variant, missense variant
rs727503500	C>A	Likely-pathogenic	Coding sequence variant, missense variant
rs727503501	C>T	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs727503503	C>T	Pathogenic	Coding sequence variant, missense variant
rs727503504	G>A,C,T	Likely-pathogenic, uncertain-significance, pathogenic	Synonymous variant, coding sequence variant, missense variant
rs727503506	C>G,T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, missense variant
rs727504242	G>A	Likely-pathogenic, uncertain-significance, pathogenic	Coding sequence variant, missense variant
rs727504243	G>A,T	Likely-pathogenic, uncertain-significance, pathogenic	Coding sequence variant, missense variant
rs727504275	C>A,T	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs727504285	G>A,C	Likely-pathogenic, uncertain-significance	Synonymous variant, coding sequence variant, missense variant
rs727504365	A>G	Likely-pathogenic	Coding sequence variant, missense variant
rs730880231	C>G,T	Pathogenic	Synonymous variant, coding sequence variant, missense variant
rs730881066	T>A	Likely-pathogenic	Coding sequence variant, missense variant
rs730881069	C>T	Conflicting-interpretations-of-pathogenicity, likely-pathogenic	Coding sequence variant, missense variant
rs730881071	G>A	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs730881072	C>T	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs730881075	G>A,C	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs730881076	T>G	Likely-pathogenic	Coding sequence variant, missense variant
rs730881077	T>C	Pathogenic	Coding sequence variant, missense variant
rs730881078	T>G	Pathogenic	Coding sequence variant, missense variant
rs730881079	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs730881081	T>C,G	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs730881082	T>A	Pathogenic	Coding sequence variant, missense variant
rs730881085	G>C	Likely-pathogenic	Coding sequence variant, missense variant
rs730881087	T>C	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs730881090	G>A,C	Likely-pathogenic	Synonymous variant, coding sequence variant, missense variant
rs730881091	C>T	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs772607683	->T	Pathogenic	Coding sequence variant, frameshift variant
rs777702465	A>T	Pathogenic	Splice donor variant
rs876661394	G>A	Likely-pathogenic, pathogenic	Coding sequence variant, stop gained
rs1057521530	C>A,G	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, missense variant, stop gained
rs1085308019	C>G,T	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs1114167340	C>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1568858210	A>G	Likely-pathogenic	Coding sequence variant, missense variant
rs1599907512	->A	Uncertain-significance, likely-pathogenic	Coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT020004	hsa-miR-375	Microarray	20215506

Transcription factors

Transcription factor	Regulation	Reference
MEF2A	Unknown	10652194
SP1	Unknown	10652194

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001570	Process	Vasculogenesis	ISS
GO:0001980	Process	Regulation of systemic arterial blood pressure by ischemic conditions	ISS
GO:0003009	Process	Skeletal muscle contraction	IBA	21873635
GO:0003779	Function	Actin binding	IDA	10806205
GO:0005515	Function	Protein binding	IPI	10806205, 12525172, 12721663, 12809519, 12840750, 16516408, 18986304, 21569246, 23369981, 25910212, 29997244, 32296183, 32814053
GO:0005829	Component	Cytosol	TAS
GO:0005861	Component	Troponin complex	IBA	21873635
GO:0005861	Component	Troponin complex	IDA	7957210, 10806205, 10850966, 12093807
GO:0006874	Process	Cellular calcium ion homeostasis	ISS
GO:0006936	Process	Muscle contraction	IBA	21873635
GO:0007507	Process	Heart development	ISS
GO:0010882	Process	Regulation of cardiac muscle contraction by calcium ion signaling	IMP	25771144
GO:0019855	Function	Calcium channel inhibitor activity	IPI	12809519
GO:0019901	Function	Protein kinase binding	IPI	12721663
GO:0019904	Function	Protein domain specific binding	IPI	11984006
GO:0030017	Component	Sarcomere	TAS	16754800
GO:0030049	Process	Muscle filament sliding	TAS
GO:0030172	Function	Troponin C binding	IPI	7957210, 11735257, 15542288
GO:0031014	Function	Troponin T binding	IPI	15542288
GO:0032780	Process	Negative regulation of ATPase activity	IDA	7957210, 11735257
GO:0032780	Process	Negative regulation of ATPase activity	IMP	10806205
GO:0046872	Function	Metal ion binding	IEA
GO:0048306	Function	Calcium-dependent protein binding	IPI	7957210
GO:0051015	Function	Actin filament binding	IPI	25771144
GO:0055010	Process	Ventricular cardiac muscle tissue morphogenesis	IMP	11815426, 16754800
GO:0060047	Process	Heart contraction	IMP	12531876
GO:0060048	Process	Cardiac muscle contraction	IBA	21873635
GO:0060048	Process	Cardiac muscle contraction	IMP	11735257
GO:0097512	Component	Cardiac myofibril	IMP	25771144
GO:1990584	Component	Cardiac Troponin complex	IMP	25771144

Other IDs

• MIM: 191044
• HGNC: 11947
• e!Ensembl: ENSG00000129991

Protein

• UniProt ID: P19429
• Protein name: Troponin I, cardiac muscle (Cardiac troponin I)
• Protein function: Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
• PDB: 1J1D, 1J1E, 1LXF, 1MXL, 1OZS, 2KGB, 2KRD, 2L1R, 2MZP, 2N7L, 4Y99, 5VLN, 5W88, 5WCL, 6KN7, 6KN8, 6MV3, 7JGI
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF11636	Troponin-I_N	1 → 31	Troponin I residues 1-32	Family
  PF00992	Troponin	46 → 177	Troponin	Family

• Sequence:

  MADGSSDAAREPRPAPAPIRRRSSNYRAYATEPHAKKKSKISASRKLQLKTLLLQIAKQE
  LEREAEERRGEKGRALSTRCQPLELAGLGFAELQDLCRQLHARVDKVDEERYDIEAKVTK
  NITEIADLTQKIFDLRGKFKRPTLRRVRISADAMMQALLGARAKESLDLRAHLKQVKKED
  TEKENREVGDWRKNIDALSGMEGRKKKFES

• Sequence length: 210