TPM1 Gene - Tropomyosin 1
Key regulator of actin filament stability in muscle and non-muscle cells; associated with cardiomyopathies and cancer
Gene Information Card
| Symbol | TPM1 |
|---|---|
| Full Name | Tropomyosin 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q22.2 |
| NCBI Gene ID | 7168 ncbi.nlm.nih.gov/gene/7168 |
| Ensembl ID | ENSG00000140416 |
| UniProt ID | P09493 |
| OMIM ID | 191010 |
| HGNC ID | 12010 |
| Aliases | CMH3, TPM1a, TPM1b, TPM1c, TPM1d, TPM1e, TPM1f, TPM1g, TPM1h, TPM1i, TPM1j, TPM1k, TPM1l, TPM1m, TPM1n, TPM1o, TPM1p, TPM1q, TPM1r, TPM1s, TPM1t, TPM1u, TPM1v, TPM1w, TPM1x, TPM1y, TPM1z |
Description
The TPM1 gene encodes tropomyosin 1, an actin-binding protein that stabilizes actin filaments and regulates actin-myosin interaction in muscle and non-muscle cells. In cardiac muscle, TPM1 is a key component of the sarcomere thin filament, where it modulates calcium-dependent contraction. Mutations in TPM1 are associated with familial hypertrophic cardiomyopathy (CMH3) and dilated cardiomyopathy. Alternative splicing generates multiple isoforms with tissue-specific expression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial hypertrophic cardiomyopathy (CMH3) | Missense mutations disrupt actin-myosin regulation, leading to sarcomere dysfunction and hypertrophy | ClinVar, OMIM |
| Dilated cardiomyopathy | Loss-of-function mutations impair thin filament stability, reducing contractile force | ClinVar, OMIM |
| Left ventricular noncompaction cardiomyopathy | Altered tropomyosin function affects myocardial development | ClinVar |
| Nemaline myopathy | Rare mutations disrupt actin binding in skeletal muscle | OMIM |
| Breast cancer | TPM1 downregulation promotes epithelial-mesenchymal transition and metastasis | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 123.4 | High |
| Skeletal muscle | 98.7 | High |
| Smooth muscle | 45.2 | Medium |
| Brain | 12.3 | Low |
| Liver | 5.6 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (AC16) | 156.8 | High expression |
| Skeletal muscle myoblasts (C2C12) | 112.3 | High expression |
| MCF7 (breast cancer) | 8.9 | Low expression |
| HeLa (cervical cancer) | 15.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.574G>A (p.Asp192Asn) | Missense | Rare | Associated with hypertrophic cardiomyopathy; disrupts actin binding |
| c.184C>T (p.Arg62Cys) | Missense | Rare | Associated with dilated cardiomyopathy; reduces thin filament stability |
| c.382G>A (p.Glu128Lys) | Missense | Rare | Associated with left ventricular noncompaction |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of function; linked to dilated cardiomyopathy |
Mutation functional classification
Loss of Function (LOF)
Start loss mutations (e.g., p.Met1Val) and truncating variants reduce TPM1 protein levels, impairing thin filament integrity in dilated cardiomyopathy.
Gain of Function (GOF)
Not well documented; most pathogenic missense mutations are dominant-negative or loss-of-function.
Dominant Negative (DN)
Missense mutations (e.g., p.Asp192Asn) produce mutant tropomyosin that incorporates into filaments and disrupts normal actin-myosin regulation, leading to hypertrophic cardiomyopathy.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cardiac muscle contraction (KEGG: hsa04260)
• Hypertrophic cardiomyopathy (KEGG: hsa05410)
• Dilated cardiomyopathy (KEGG: hsa05414)
• Actin cytoskeleton regulation (KEGG: hsa04810)
Protein Summary
Tropomyosin 1 is a 284-amino acid coiled-coil protein that forms head-to-tail polymers along actin filaments. It stabilizes F-actin and regulates myosin access in a calcium-dependent manner via troponin. In cardiac muscle, TPM1 is essential for sarcomere function. Alternative splicing produces isoforms with distinct tissue distributions and functions. Mutations in TPM1 cause inherited cardiomyopathies by disrupting thin filament regulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TPM1 Knockout HEK293 Cell Line | EDJ-KQ5956 | Human | 7168 | Details Get a Quote |
| TPM1 Knockout A-549 Cell Line | EDJ-KQ29516 | Human | 7168 | Details Get a Quote |
| TPM1 Knockout HCT 116 Cell Line | EDJ-KQ29517 | Human | 7168 | Details Get a Quote |
| TPM1 Knockout HeLa Cell Line | EDJ-KQ29518 | Human | 7168 | Details Get a Quote |
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