A comprehensive guide to genetic variants and post-translational modifications of cardiac troponin C.
Cardiac troponin C (cTnC)
Cardiomyopathy
Genetic variant
Heart
Post-translational modification
TNNC1
Journal
Journal of muscle research and cell motility
ISSN: 1573-2657
Titre abrégé: J Muscle Res Cell Motil
Pays: Netherlands
ID NLM: 8006298
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
14
06
2020
accepted:
24
10
2020
pubmed:
13
11
2020
medline:
18
1
2022
entrez:
12
11
2020
Statut:
ppublish
Résumé
Familial cardiomyopathy is an inherited disease that affects the structure and function of heart muscle and has an extreme range of phenotypes. Among the millions of affected individuals, patients with hypertrophic (HCM), dilated (DCM), or left ventricular non-compaction (LVNC) cardiomyopathy can experience morphologic changes of the heart which lead to sudden death in the most detrimental cases. TNNC1, the gene that codes for cardiac troponin C (cTnC), is a sarcomere gene associated with cardiomyopathies in which probands exhibit young age of presentation and high death, transplant or ventricular fibrillation events relative to TNNT2 and TNNI3 probands. Using GnomAD, ClinVar, UniProt and PhosphoSitePlus databases and published literature, an extensive list to date of identified genetic variants in TNNC1 and post-translational modifications (PTMs) in cTnC was compiled. Additionally, a recent cryo-EM structure of the cardiac thin filament regulatory unit was used to localize each functionally studied amino acid variant and each PTM (acetylation, glycation, s-nitrosylation, phosphorylation) in the structure of cTnC. TNNC1 has a large number of variants (> 100) relative to other genes of the same transcript size. Surprisingly, the mapped variant amino acids and PTMs are distributed throughout the cTnC structure. While many cardiomyopathy-associated variants are localized in α-helical regions of cTnC, this was not statistically significant χ
Identifiants
pubmed: 33179204
doi: 10.1007/s10974-020-09592-5
pii: 10.1007/s10974-020-09592-5
pmc: PMC8110610
mid: NIHMS1646060
doi:
Substances chimiques
Troponin C
0
Troponin I
0
Troponin T
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
323-342Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL128683
Pays : United States
Informations de copyright
© 2020. Springer Nature Switzerland AG.
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