TPM2 Gene

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1		Rui Liu	+ 415 word(s)	415	2020-12-15 08:12:59

This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/tpm2

Tropomyosin 2: The TPM2 gene provides instructions for making a protein called beta (β)-tropomyosin, which is part of the tropomyosin protein family.

genes

1. Normal Function

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.

2. Health Conditions Related to Genetic Changes

2.1. Cap myopathy

At least three TPM2 gene mutations have been identified in people with cap myopathy, a disorder that leads to muscle weakness (myopathy) and poor muscle tone (hypotonia). 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.

2.2. Distal arthrogryposis type 1

At least three mutations in the TPM2 gene have been found to cause distal arthrogryposis type 1, a disorder characterized by joint deformities (contractures) in the hands and feet. It is unclear how these mutations lead 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.

2.3. Sheldon-Hall syndrome

At least six TPM2 gene mutations have been identified in people with Sheldon-Hall syndrome, a muscle and skeletal disorder similar to distal arthrogryposis type 1 (described above) that impairs joint movement in the hands and feet. Mutations in the TPM2 gene may alter the structure of β-tropomyosin and disrupt the protein's normal function in controlling muscle contractions, resulting in the contractures and other muscle and skeletal abnormalities associated with this condition.

Congenital fiber-type disproportion

Nemaline myopathy

3. Other Names for This Gene

beta-tropomyosin
NEM4
TMSB
TPM2_HUMAN
tropomyosin 2 (beta)
tropomyosin beta chain
tropomyosin, skeletal muscle beta
tropomyosin-2

References

Beck AE, McMillin MJ, Gildersleeve HI, Kezele PR, Shively KM, Carey JC,Regnier M, Bamshad MJ. Spectrum of mutations that cause distal arthrogryposistypes 1 and 2B. Am J Med Genet A. 2013 Mar;161A(3):550-5. doi:10.1002/ajmg.a.35809.
Clarke NF, Domazetovska A, Waddell L, Kornberg A, McLean C, North KN. Capdisease 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.
Donner K, Ollikainen M, Ridanpää M, Christen HJ, Goebel HH, de Visser M, PelinK, Wallgren-Pettersson C. Mutations in the beta-tropomyosin (TPM2) gene--a rarecause of nemaline myopathy. Neuromuscul Disord. 2002 Feb;12(2):151-8.
Goebel HH. Cap disease uncapped. Neuromuscul Disord. 2007 Jun;17(6):429-32.
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 thebeta-tropomyosin gene TPM2. Neuromuscul Disord. 2007 Jun;17(6):433-42.
Marttila M, Lemola E, Wallefeld W, Memo M, Donner K, Laing NG, Marston S,Grönholm M, Wallgren-Pettersson C. Abnormal actin binding of aberrantβ-tropomyosins is a molecular cause of muscle weakness in TPM2-related nemalineand cap myopathy. Biochem J. 2012 Feb 15;442(1):231-9. doi: 10.1042/BJ20111030.
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 withnemaline myopathy. Neuromuscul Disord. 2009 Feb;19(2):118-23. doi:10.1016/j.nmd.2008.11.009.
Ochala J. Thin filament proteins mutations associated with skeletalmyopathies: defective regulation of muscle contraction. J Mol Med (Berl). 2008Nov;86(11):1197-204. doi: 10.1007/s00109-008-0380-9.
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 capdisease associated with beta-tropomyosin (TPM2) mutations. Neurology. 2008 Dec2;71(23):1896-901. doi: 10.1212/01.wnl.0000336654.44814.b8.
Sung SS, Brassington AM, Grannatt K, Rutherford A, Whitby FG, Krakowiak PA,Jorde LB, Carey JC, Bamshad M. Mutations in genes encoding fast-twitchcontractile proteins cause distal arthrogryposis syndromes. Am J Hum Genet. 2003 Mar;72(3):681-90.
Tajsharghi H, Kimber E, Holmgren D, Tulinius M, Oldfors A. Distalarthrogryposis and muscle weakness associated with a beta-tropomyosin mutation.Neurology. 2007 Mar 6;68(10):772-5.
Tajsharghi H, Ohlsson M, Lindberg C, Oldfors A. Congenital myopathy withnemaline rods and cap structures caused by a mutation in the beta-tropomyosingene (TPM2). Arch Neurol. 2007 Sep;64(9):1334-8.

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Rui Liu

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Entry Collection: MedlinePlus

Update Date: 25 Dec 2020

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