ACTG1

ACTG1 Background

The ACTG1 gene encodes the cytoskeletal protein gamma-actin, which plays an important role in determining cell shape and controlling cell movement. Gamma-actin protein also refers to as ACTG1. Human gamma-actin is 41.8 kDa in molecular weight and 375 amino acids in length. Gamma-actin is widely expressed in cellular cytoskeletons of many tissues, particularly abundant in the auditory hair cells of the cochlea ^[1]. The hair cells are essential for normal hearing. Mutations in ACTG1 are associated with DFNA20/26, a subtype of autosomal dominant non-syndromic sensorineural progressive hearing loss ^[1][2][6]. And Baraitser-Winter syndrome is also linked to ACTG1 mutations ^[3]. Studies have identified ACTG1 with significantly high expression in skin cancer tissue and suggested that ACTG1 can regulate cell proliferation and migration through the ROCK signaling pathway ^[4]. And other studies have shown that ACTG1 recurrent mutation leads to isolated ocular coloboma (OC), a defect in optic fissure closure that is a common cause of severe congenital visual impairment ^[5]. Kevin J. Sonnemann et al. observed that skeletal muscle-specific cytoplasmic γ-Actin knockout (Actg1-msKO) mice dysfunctioned in whole-body tension and isometric twitch force, although their muscle development proceeded normally. They concluded that cytoplasmic γ-Actin is not required for skeletal muscle development but its absence leads to a progressive myopathy ^[7].

[1] Lee CG, Jang J, et al. A novel missense mutation in the ACTG1 gene in a family with congenital autosomal dominant deafness: A case report [J]. Mol Med Rep. 2018 Jun;17(6):7611-7617.
[2] Liu, P., Li, H., et al. Novel ACTG1 mutation causing autosomal dominant non-syndromic hearing impairment in a Chinese family [J]. J Genets Genomics 35, 2008, 553-558.
[3] Riviere, J.B., van Bon, B.W., et al. De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome [J]. Nat Genet 44, 2012, 440–444, S441-S442.
[4] Xinqian Dong Yingsheng Han, et al. Actin Gamma 1, a new skin cancer pathogenic gene, identified by the biological feature?based classification [J]. J Cell Biochem. 2018 Feb;119(2):1406-1419.
[5] Rainger J, Williamson KA, et al. A recurrent de novo mutation in ACTG1 causes isolated ocular coloboma [J]. Hum Mutat. 2017 Aug;38(8):942-946.
[6] Zhu, M., Yang, T., Wei, et al. Mutations in the gamma-actin gene (ACTG1) are associated with dominant progressive deafness (DFNA20/26) [J]. Am. J. Hum. Genet. 2003, 73: 1082-1091.
[7] Sonnemann KJ, Fitzsimons DP, et al. Cytoplasmic gamma-actin is not required for skeletal muscle development but its absence leads to a progressive myopathy [J]. Developmental Cell. Sep. 2006, 11 (3): 387-97.