TGFB2

Chr 1AD

transforming growth factor beta 2

Also known as: CAEND2, G-TSF, LDS4, TGF-beta2

NCBI Gene: 7042 ENSG00000092969 UniProt: P61812 OMIM: 190220

The protein functions as a secreted ligand that binds TGF-beta receptors to activate SMAD transcription factors and regulate gene expression throughout development. Mutations cause Camurati-Engelmann disease 2 (a bone dysplasia) and Loeys-Dietz syndrome 4 (a connective tissue disorder affecting the cardiovascular system, skeleton, and other organs), both inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function variation in the general population.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGF-beta family members. Disruption of the TGF-beta/SMAD pathway has been implicated in a variety of human cancers. A chromosomal translocation that includes this gene is associated with Peters' anomaly, a congenital defect of the anterior chamber of the eye. Mutations in this gene may be associated with Loeys-Dietz syndrome. This gene encodes multiple isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Aug 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Camurati-Engelmann disease 2MIM #606631

Loeys-Dietz syndrome 4MIM #614816

Clinical highlights

Gene-disease validity (ClinGen)

familial thoracic aortic aneurysm and aortic dissection · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

144

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.15

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖