TGFB1 gene

TGFB1 gene is a gene located on chromosome 19q13.2 that encodes the eponymous protein TGFB1. Ligands of this protein family(transforming growth factor: 3 isoforms exist) bind different TGF-beta receptors, leading to the recruitment and activation of transcription factors of the SMAD family, which regulate gene expression.

The encoded preprotein is proteolytically processed to generate a latent-associated peptide (LAP) and a mature peptide. It is present either in a latent form consisting of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting of only the mature peptide homodimer.

The mature peptide may also form heterodimers with other members of the TGFB family . The encoded protein regulates cell proliferation, differentiation, and growth and may modulate the expression and activation of other growth factors such as interferon gamma and tumor necrosis factor-alpha. The TGFB1 gene is frequently upregulated in tumor cells.

Mutations in the TGFB1 gene are associated with leading Camurati-Engelmann disease (Hughes Pet al 2019). Other associations include inflammatory bowel disease and encephalopathy, progressive pulmonary fibrosis (Ask K et al. 2008), corneal dystrophy type I (Hilton EN et al. 2007), and otosclerosis (Priyadarshi S et al. 2016).

Corneal dystrophy type I is a very rare congenital form of granular corneal dystrophy with multiple small superficial deposits centrally in the stroma of the cornea.

1. Ask K et al. (2008) Progressive pulmonary fibrosis is mediated by TGF-beta isoform 1 but not TGF-beta3. Int J Biochem Cell Biol 40:484-495.
2. Biler ED et al (2018) <i>TGFB1</i> and <i>LAMA1 gene</i> polymorphisms in children with high myopia. Pak J Med Sci 34:463-467.
3. Hilton EN et al (2007) De novo mutation in the BIGH3/TGFB1 gene causing granular corneal dystrophy. Br J Ophthalmol 91:1083-1084.
4. Hughes Pet al. (2019) Observations on the natural history of Camurati-Engelmann disease. J Bone Miner Res 34:875-882.
5. Kotlarz D et al (2018) Human TGF-β1 deficiency causes severe inflammatory bowel disease and encephalopathy. Nat Genet 50:344-348.
6. Priyadarshi S et al (2016) Otosclerosis Associated with a De Novo Mutation -832G > A in the TGFB1 Gene Promoter Causing a Decreased Expression Level. Sci Rep 6:29572.
7. Oueslati S et al. (2015) Association of TGFB1 -509C/T polymorphism gene with clinical variability in cystic fibrosis patients: A case-control study. Pathol Biol (Paris) 63(4-5):175-178.