Reviewed April 2012
What is the official name of the TPM2 gene?
The official name of this gene is “tropomyosin 2 (beta).”
TPM2 is the gene's official symbol. The TPM2 gene is also known by other names, listed below.
What is the normal function of the TPM2 gene?
The TPM2 gene provides instructions for making a protein called beta (β)-tropomyosin, which is part of the tropomyosin protein family. Tropomyosin proteins regulate the tensing of muscle fibers (muscle contraction) by controlling the binding of two muscle proteins, myosin and actin. In non-muscle cells, tropomyosin proteins play a role in controlling cell shape.
β-tropomyosin is found primarily in skeletal muscles, which are the muscles used for movement. This protein helps regulate muscle contraction by interacting with other muscle proteins, particularly myosin and actin. These interactions are essential for stabilizing and maintaining structures called sarcomeres within muscle cells. Sarcomeres are the basic units of muscle contraction; they are made of proteins that generate the mechanical force needed for muscles to contract.
How are changes in the TPM2 gene related to health conditions?
- cap myopathy - caused by mutations in the TPM2 gene
At least three TPM2 gene mutations have been identified in people with cap myopathy. These mutations delete or duplicate genetic material in the TPM2 gene or replace single protein building blocks (amino acids) in the β-tropomyosin protein sequence. The specific effects of these TPM2 gene mutations are unclear, but researchers suggest they may interfere with normal actin-myosin binding, impairing muscle contraction and resulting in the muscle weakness that occurs in cap myopathy.
- distal arthrogryposis type 1 - caused by mutations in the TPM2 gene
At least one mutation in the TPM2 gene has been found to cause distal arthrogryposis type 1, a disorder characterized by joint deformities (contractures) in the hands and feet. The mutation changes a single amino acid in the β-tropomyosin protein. Specifically, it replaces the amino acid arginine with the amino acid glycine at protein position 91 (written as Arg91Gly or R91G). It is unclear how the defective protein leads to contractures in people with distal arthrogryposis type 1, or why the joint problems are typically limited to the hands and feet. However, researchers speculate that contractures may be related to problems with muscle contraction that limit the movement of joints before birth.
- other disorders - caused by mutations in the TPM2 gene
TPM2 gene mutations have also been found to cause several other muscle disorders (myopathies), including nemaline myopathy and a more severe form of distal arthrogryposis known as type 2B. These disorders are characterized by muscle weakness and problems with movement. Because their signs and symptoms are present from birth, these disorders are known as congenital myopathies.
Most of the mutations that have been identified in the TPM2 gene change single amino acids in the β-tropomyosin protein. Mutations in this gene likely alter the structure of β-tropomyosin and disrupt the protein's normal function. However, the mechanism by which defective β-tropomyosin causes muscle weakness is unknown. Researchers are working to determine how different mutations in the TPM2 gene lead to different congenital myopathies.
Where is the TPM2 gene located?
Cytogenetic Location: 9p13
Molecular Location on chromosome 9: base pairs 35,681,992 to 35,690,055
The TPM2 gene is located on the short (p) arm of chromosome 9 at position 13.
More precisely, the TPM2 gene is located from base pair 35,681,992 to base pair 35,690,055 on chromosome 9.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about TPM2?
You and your healthcare professional may find the following resources about TPM2 helpful.
Educational resources - Information pages
- Molecular Biology of the Cell (fourth edition, 2000): Role of Tropomyosin and Troponin in Skeletal Muscle Contraction (http://www.ncbi.nlm.nih.gov/books/NBK21670/)
- The Cell: A Molecular Approach (second edition, 2000): Association of Tropomyosin and Troponins with Actin Filaments (Figure) (http://www.ncbi.nlm.nih.gov/books/NBK9961/?rendertype=figure&id=A1799)
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1288)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for TPM2 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=7169%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28%28TPM2%5BTIAB%5D%29%20OR%20%28tropomyosin%202%5BTIAB%5D%29%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/190990)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_TPM2.html)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=7169)
- HGNC Gene Family: Tropomyosins (http://www.genenames.org/genefamilies/TPM)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=12011)
- Leiden Muscular Dystrophy Page: TPM2 (http://www.dmd.nl/nmdb2/home.php?select_db=TPM2)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7169)
What other names do people use for the TPM2 gene or gene products?
- tropomyosin beta chain
- tropomyosin, skeletal muscle beta
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding TPM2?
amino acid ;
muscle cells ;
protein sequence ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Clarke NF, Domazetovska A, Waddell L, Kornberg A, McLean C, North KN. Cap disease due to mutation of the beta-tropomyosin gene (TPM2). Neuromuscul Disord. 2009 May;19(5):348-51. doi: 10.1016/j.nmd.2009.03.003. Epub 2009 Apr 3. (http://www.ncbi.nlm.nih.gov/pubmed/19345583?dopt=Abstract)
- Donner K, Ollikainen M, Ridanpää M, Christen HJ, Goebel HH, de Visser M, Pelin K, Wallgren-Pettersson C. Mutations in the beta-tropomyosin (TPM2) gene--a rare cause of nemaline myopathy. Neuromuscul Disord. 2002 Feb;12(2):151-8. (http://www.ncbi.nlm.nih.gov/pubmed/11738357?dopt=Abstract)
- Goebel HH. Cap disease uncapped. Neuromuscul Disord. 2007 Jun;17(6):429-32. Epub 2007 Apr 16. (http://www.ncbi.nlm.nih.gov/pubmed/17434306?dopt=Abstract)
- Lehtokari VL, Ceuterick-de Groote C, de Jonghe P, Marttila M, Laing NG, Pelin K, Wallgren-Pettersson C. Cap disease caused by heterozygous deletion of the beta-tropomyosin gene TPM2. Neuromuscul Disord. 2007 Jun;17(6):433-42. Epub 2007 Apr 16. (http://www.ncbi.nlm.nih.gov/pubmed/17434307?dopt=Abstract)
- Marttila M, Lemola E, Wallefeld W, Memo M, Donner K, Laing NG, Marston S, Grönholm M, Wallgren-Pettersson C. Abnormal actin binding of aberrant β-tropomyosins is a molecular cause of muscle weakness in TPM2-related nemaline and cap myopathy. Biochem J. 2012 Feb 15;442(1):231-9. doi: 10.1042/BJ20111030. (http://www.ncbi.nlm.nih.gov/pubmed/22084935?dopt=Abstract)
- Monnier N, Lunardi J, Marty I, Mezin P, Labarre-Vila A, Dieterich K, Jouk PS. Absence of beta-tropomyosin is a new cause of Escobar syndrome associated with nemaline myopathy. Neuromuscul Disord. 2009 Feb;19(2):118-23. doi: 10.1016/j.nmd.2008.11.009. Epub 2009 Jan 19. (http://www.ncbi.nlm.nih.gov/pubmed/19155175?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7169)
- Ochala J. Thin filament proteins mutations associated with skeletal myopathies: defective regulation of muscle contraction. J Mol Med (Berl). 2008 Nov;86(11):1197-204. doi: 10.1007/s00109-008-0380-9. Epub 2008 Jun 24. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18574571?dopt=Abstract)
- Ohlsson M, Quijano-Roy S, Darin N, Brochier G, Lacène E, Avila-Smirnow D, Fardeau M, Oldfors A, Tajsharghi H. New morphologic and genetic findings in cap disease associated with beta-tropomyosin (TPM2) mutations. Neurology. 2008 Dec 2;71(23):1896-901. doi: 10.1212/01.wnl.0000336654.44814.b8. (http://www.ncbi.nlm.nih.gov/pubmed/19047562?dopt=Abstract)
- Sung SS, Brassington AM, Grannatt K, Rutherford A, Whitby FG, Krakowiak PA, Jorde LB, Carey JC, Bamshad M. Mutations in genes encoding fast-twitch contractile proteins cause distal arthrogryposis syndromes. Am J Hum Genet. 2003 Mar;72(3):681-90. (http://www.ncbi.nlm.nih.gov/pubmed/12592607?dopt=Abstract)
- Tajsharghi H, Kimber E, Holmgren D, Tulinius M, Oldfors A. Distal arthrogryposis and muscle weakness associated with a beta-tropomyosin mutation. Neurology. 2007 Mar 6;68(10):772-5. (http://www.ncbi.nlm.nih.gov/pubmed/17339586?dopt=Abstract)
- Tajsharghi H, Ohlsson M, Lindberg C, Oldfors A. Congenital myopathy with nemaline rods and cap structures caused by a mutation in the beta-tropomyosin gene (TPM2). Arch Neurol. 2007 Sep;64(9):1334-8. (http://www.ncbi.nlm.nih.gov/pubmed/17846275?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.