The LTBP4 gene provides instructions for making a protein that has multiple functions in the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells. The LTBP4 protein controls the activity of a protein called transforming growth factor beta-1 (TGFβ-1) by attaching it to the extracellular matrix. This growth factor is turned off (inactivated) when stored in the extracellular matrix and turned on (activated) when released. When turned on, the TGFβ-1 protein triggers chemical signals that direct the functions of the body's cells during growth and development and that regulate the formation of the extracellular matrix.
The LTBP4 protein also plays a critical role in the formation of elastic fibers in the extracellular matrix. Elastic fibers are slender bundles of proteins that provide strength and flexibility to connective tissue, which supports organs and tissues such as the skin, lungs, heart, ligaments, and blood vessels.
Health Conditions Related to Genetic Changes
At least 20 variants (also known as mutations) in the LTBP4 gene have been identified in people with cutis laxa. LTBP4 gene variants cause a form of the disorder called autosomal recessive cutis laxa type 1C (ARCL1C) or Urban-Rifkin-Davis syndrome, which is characterized by loose and sagging skin, a lung disease called emphysema, and abnormalities involving the digestive and urinary systems.
Most of the LTBP4 gene variants involved in cutis laxa change single DNA building blocks. These changes alter the blueprint for making proteins, and the abnormal blueprint is broken down in the cell before LTBP4 protein is made. A shortage of this protein prevents the assembly of elastic fibers, which weakens connective tissue in the skin, lungs, and other organs. These defects in connective tissue underlie the major features of ARCL1C.More About This Health Condition
Other Names for This Gene
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Callewaert BL, Urban Z. LTBP4-Related Cutis Laxa. 2016 Feb 11 [updated 2021 Jul 22]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from http://www.ncbi.nlm.nih.gov/books/NBK343782/ Citation on PubMed
- Dabovic B, Chen Y, Choi J, Vassallo M, Dietz HC, Ramirez F, von Melchner H, Davis EC, Rifkin DB. Dual functions for LTBP in lung development: LTBP-4 independently modulates elastogenesis and TGF-beta activity. J Cell Physiol. 2009 Apr;219(1):14-22. doi: 10.1002/jcp.21643. Citation on PubMed
- Noda K, Dabovic B, Takagi K, Inoue T, Horiguchi M, Hirai M, Fujikawa Y, Akama TO, Kusumoto K, Zilberberg L, Sakai LY, Koli K, Naitoh M, von Melchner H, Suzuki S, Rifkin DB, Nakamura T. Latent TGF-β binding protein 4 promotes elastic fiber assembly by interacting with fibulin-5. Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):2852-7. doi: 10.1073/pnas.1215779110. Epub 2013 Feb 4. Citation on PubMed
- Urban Z, Hucthagowder V, Schürmann N, Todorovic V, Zilberberg L, Choi J, Sens C, Brown CW, Clark RD, Holland KE, Marble M, Sakai LY, Dabovic B, Rifkin DB, Davis EC. Mutations in LTBP4 cause a syndrome of impaired pulmonary, gastrointestinal, genitourinary, musculoskeletal, and dermal development. Am J Hum Genet. 2009 Nov;85(5):593-605. doi: 10.1016/j.ajhg.2009.09.013. Epub 2009 Oct 15. Citation on PubMed