TNNT3: Troponin T3, Fast Skeletal Type
Gene encoding the fast skeletal muscle troponin T isoform, critical for muscle contraction and implicated in distal arthrogryposis and nemaline myopathy.
Gene Information Card
| Symbol | TNNT3 |
|---|---|
| Full Name | Troponin T3, fast skeletal type |
| Gene Type | protein-coding |
| Chromosomal Location | 11p15.5 |
| NCBI Gene ID | 7140 ncbi.nlm.nih.gov/gene/7140 |
| Ensembl ID | ENSG00000130595 |
| UniProt ID | P45378 |
| OMIM ID | 600692 |
| HGNC ID | 11950 |
| Aliases | TnTf, AMCD2B, DA2B, FSSV, MGC126696, MGC126698 |
Description
TNNT3 encodes the fast skeletal muscle isoform of troponin T, a component of the troponin complex that regulates calcium-mediated muscle contraction. This isoform is expressed predominantly in fast-twitch skeletal muscle fibers. Mutations in TNNT3 are associated with distal arthrogryposis type 2B (DA2B) and nemaline myopathy. The gene spans approximately 18 kb on chromosome 11p15.5 and contains 14 exons. Alternative splicing generates multiple isoforms with distinct functional properties.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Distal Arthrogryposis Type 2B (DA2B) | Missense mutations in TNNT3 disrupt calcium sensitivity and cross-bridge cycling, leading to impaired muscle relaxation and joint contractures. | ClinVar, OMIM #600692 |
| Nemaline Myopathy | Dominant-negative mutations (e.g., p.Arg63His) alter thin filament assembly and cause nemaline rod formation in fast skeletal muscle fibers. | ClinVar, OMIM #600692 |
| Arthrogryposis Multiplex Congenita, Distal Type 2B | Same as DA2B; mutations in TNNT3 cause autosomal dominant distal arthrogryposis with characteristic hand and foot contractures. | OMIM #600692 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle (fast fibers) | 150.2 | High |
| Heart | 1.8 | Low |
| Brain | 0.3 | Not detected |
| Liver | 0.1 | Not detected |
| Kidney | 0.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| LHCN-M2 (skeletal muscle myotubes) | 120.5 | Differentiated myotubes |
| C2C12 (mouse myoblasts) | 95.3 | After differentiation |
| HeLa | 0.5 | Negligible |
| HEK293 | 0.3 | Negligible |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.187C>T (p.Arg63His) | Missense | Rare | Dominant-negative; causes nemaline myopathy |
| c.209A>G (p.Asn70Ser) | Missense | Rare | Associated with DA2B; alters calcium sensitivity |
| c.517G>A (p.Glu173Lys) | Missense | Rare | Associated with DA2B; reduces troponin I binding |
| c.674C>T (p.Thr225Met) | Missense | Rare | Associated with DA2B; impairs relaxation |
Mutation functional classification
Loss of Function (LOF)
No clear loss-of-function mutations reported; TNNT3 is essential for muscle contraction and null alleles are likely lethal.
Gain of Function (GOF)
Not described; mutations typically alter calcium sensitivity rather than gain novel function.
Dominant Negative (DN)
p.Arg63His and other missense mutations act via dominant-negative mechanism, disrupting thin filament regulation and causing nemaline myopathy or distal arthrogryposis.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Muscle contraction (Reactome R-HSA-397014)
• Cardiac conduction (Reactome R-HSA-5576891)
• Striated muscle contraction (KEGG hsa04260)
Protein Summary
Troponin T3 (TnTf) is a 278-amino acid protein (isoform 1) that anchors the troponin complex to tropomyosin on the thin filament of fast skeletal muscle sarcomeres. It contains a hypervariable N-terminal region that undergoes alternative splicing, modulating calcium sensitivity. The protein interacts with troponin I, troponin C, and tropomyosin to regulate actin-myosin cross-bridge formation. Mutations in the N-terminal domain (e.g., p.Arg63His) disrupt thin filament regulation, leading to muscle weakness and contractures.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNNT3 Knockout HEK293 Cell Line | EDJ-KQ15876 | Human | 7140 | Details Get a Quote |
| TNNT3 Knockout HeLa Cell Line | EDJ-KQ54681 | Human | 7140 | Details Get a Quote |
| TNNT3 Knockout A-549 Cell Line | EDJ-KQ63164 | Human | 7140 | Details Get a Quote |
| TNNT3 Knockout HCT 116 Cell Line | EDJ-KQ71638 | Human | 7140 | Details Get a Quote |
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