TNNT2

TNNT2 or Cardiac Troponin T is a protein encoded by the TNNT2 gene in humans. It is a critical component of the troponin complex, which regulates the contraction of striated muscle. In the heart, TNNT2 plays a vital role in the contraction of cardiac muscle by controlling the calcium sensitivity of myofilaments. Mutations in the TNNT2 gene are associated with various cardiomyopathies, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM), making it an important marker for cardiac health and disease.

Structure

The TNNT2 protein is part of the troponin complex, which also includes troponin I (TnI) and troponin C (TnC). This complex is located on the thin filament of striated muscles and is essential for muscle contraction. TNNT2 binds to tropomyosin, helping to position the troponin complex on the actin filament, and plays a key role in the regulation of muscle contraction and relaxation through its interactions with TnI and TnC.

Function

The primary function of TNNT2 is to regulate cardiac muscle contraction. Upon an increase in intracellular calcium concentration, calcium binds to TnC, causing a conformational change in the troponin complex. This change moves tropomyosin away from actin's myosin-binding sites, allowing myosin to bind to actin and initiate muscle contraction. TNNT2 modulates this process by anchoring the troponin complex to tropomyosin and actin, and by transmitting the conformational changes within the complex.

Clinical Significance

Mutations in the TNNT2 gene are linked to several forms of cardiomyopathy, which are diseases of the heart muscle that can lead to heart failure.

• Hypertrophic Cardiomyopathy (HCM): Mutations in TNNT2 are one of the genetic causes of HCM, characterized by the thickening of the heart muscle, which can obstruct blood flow and lead to sudden cardiac death.
• Dilated Cardiomyopathy (DCM): Certain mutations in TNNT2 can cause DCM, a condition where the heart's ability to pump blood is decreased because the heart's main pumping chamber is enlarged and weakened.
• Restrictive Cardiomyopathy (RCM): Though less common, mutations in TNNT2 can also lead to RCM, where the heart is unable to fill properly with blood because the heart muscle is stiff.

Additionally, levels of cardiac troponin T, including isoforms produced by alternative splicing of the TNNT2 gene, are used clinically as a biomarker for myocardial infarction (heart attack) and other conditions involving cardiac injury.

Genetics

The TNNT2 gene is located on chromosome 1q32.1 and consists of multiple exons that undergo alternative splicing, producing different isoforms of the TNNT2 protein. These isoforms may have distinct functions or regulatory mechanisms in cardiac muscle tissue. Genetic variations and mutations in TNNT2 can affect the structure and function of the cardiac troponin T protein, leading to altered cardiac muscle contraction and cardiomyopathy.

Research Directions

Research on TNNT2 continues to focus on understanding the molecular mechanisms by which mutations cause cardiomyopathies and on developing targeted therapies. Studies are also exploring the role of TNNT2 in cardiac development and its potential as a therapeutic target for heart failure.

Cardiovascular disease A-Z

Most common cardiac diseases

• Cardiac arrhythmia‎
• Cardiogenetic disorders‎
• Cardiomegaly‎
• Cardiomyopathy‎
• Cardiopulmonary resuscitation‎
• Chronic rheumatic heart diseases‎
• Congenital heart defects‎
• Heart neoplasia‎
• Ischemic heart diseases‎
• Pericardial disorders
• Syndromes affecting the heart‎
• Valvular heart disease‎

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z

A

• Accelerated idioventricular rhythm
• Acute decompensated heart failure
• Arteriosclerotic heart disease
• Athletic heart syndrome
• Atrial flutter
• Atrioventricular fistula
• Cardiovascular disease in Australia
• Autoimmune heart disease

B

• Brown atrophy of the heart

C

• Ebb Cade
• Cardiac allograft vasculopathy
• Cardiac amyloidosis
• Cardiac asthma
• Cardiac tamponade
• Cardiogenic shock
• Cardiogeriatrics
• Cardiorenal syndrome
• Cardiotoxicity
• Carditis
• Coronary artery aneurysm
• Coronary artery anomaly
• Coronary artery disease
• Spontaneous coronary artery dissection
• Coronary artery ectasia
• Coronary occlusion
• Coronary steal
• Coronary thrombosis
• Coronary vasospasm
• Cœur en sabot
• Coxsackievirus-induced cardiomyopathy

D

• Duke Treadmill Score
• Duroziez's disease

E

• Eisenmenger's syndrome
• Embryocardia
• Endocardial fibroelastosis
• Eosinophilic myocarditis

H

• Heart attack
• Heart failure
• Heart failure with preserved ejection fraction
• Heart to Heart (1949 film)
• High-output heart failure
• Hyperdynamic precordium

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z

I

• Idiopathic giant-cell myocarditis
• Interventricular dyssynchrony
• Intraventricular dyssynchrony
• Isolated atrial amyloidosis

K

• Keshan disease

L

• Loeffler endocarditis

M

• Mydicar
• Myocardial bridge
• Myocardial disarray
• Myocardial rupture
• Myocardial scarring
• Myocardial stunning
• Myocarditis

N

• Nonbacterial thrombotic endocarditis

O

• OLR1
• Ostial disease

P

• Papillary fibroelastoma
• Pathophysiology of heart failure
• Postpericardiotomy syndrome
• Pulmonary vein stenosis

R

• Right axis deviation
• Roemheld syndrome

S

• Saturated fat and cardiovascular disease
• SCAR-Fc
• Shone's syndrome
• Strain pattern
• Subacute bacterial endocarditis
• Sudden cardiac death of athletes

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z

T

• Traumatic cardiac arrest

V

• Ventricular aneurysm
• Vibroacoustic disease
• Viral cardiomyopathy

W

• Waon therapy