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Normal Function
The ADAMTSL2 gene provides instructions for making a protein whose exact function is unknown. The ADAMTSL2 protein is active in many different tissues and is found in the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells.
Studies suggest that the ADAMTSL2 protein interacts with a protein called latent transforming growth factor beta-binding protein 1 (LTBP1). The LTBP1 protein is involved in the storage of another protein called transforming growth factor beta (TGF-β). TGF-β helps regulate important cell processes, including the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement, and the self-destruction of cells (apoptosis).
The interaction between the ADAMTSL2 and LTBP1 proteins suggests that ADAMTSL2 may play a role in the microfibrillar network. This organized arrangement of thread-like filaments (microfibrils) within the extracellular matrix provides strength and flexibility to tissues throughout the body.
Researchers also suspect that the ADAMTSL2 protein may help regulate the availability of TGF-β, which is stored in the microfibrillar network. Once released from the microfibrillar network, TGF-β activates important signaling pathways, including the signaling pathways involved in bone formation.
Health Conditions Related to Genetic Changes
Geleophysic dysplasia
Variants (also called mutations) in the ADAMTSL2 gene can cause geleophysic dysplasia, which is characterized by abnormalities of the bones, joints, heart, and skin. ADAMTSL2 gene variants lead to changes in the ADAMTSL2 protein that likely alter the protein’s 3-dimensional shape, which impairs its ability to function properly.
ADAMTSL2 proteins that do not function properly can disrupt the microfibrillar network in various tissues, although this process is not well understood. This impairs normal cell function, which contributes to the various signs and symptoms of geleophysic dysplasia. Researchers are working to determine exactly how variants in the ADAMTSL2 gene lead to the characteristic features of this condition.
More About This Health ConditionOther Names for This Gene
- KIAA0605
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Camarena V, Williams MM, Morales AA, Zafeer MF, Kilic OV, Kamiar A, Abad C, Rasmussen MA, Briski LM, Peart L, Bademci G, Barbouth DS, Smithson S, Wang G, Shehadeh LA, Walz K, Tekin M. ADAMTSL2 mutations determine the phenotypic severity in geleophysic dysplasia. JCI Insight. 2024 Feb 1;9(5):e174417. doi: 10.1172/jci.insight.174417. Citation on PubMed
- Le Goff C, Morice-Picard F, Dagoneau N, Wang LW, Perrot C, Crow YJ, Bauer F, Flori E, Prost-Squarcioni C, Krakow D, Ge G, Greenspan DS, Bonnet D, Le Merrer M, Munnich A, Apte SS, Cormier-Daire V. ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF-beta bioavailability regulation. Nat Genet. 2008 Sep;40(9):1119-23. doi: 10.1038/ng.199. Citation on PubMed or Free article on PubMed Central
- Marzin P, Cormier-Daire V. Geleophysic Dysplasia. 2009 Sep 22 [updated 2024 Mar 28]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK11168/ Citation on PubMed
- Piccolo P, Sabatino V, Mithbaokar P, Polishchuck E, Law SK, Magraner-Pardo L, Pons T, Polishchuck R, Brunetti-Pierri N. Geleophysic dysplasia: novel missense variants and insights into ADAMTSL2 intracellular trafficking. Mol Genet Metab Rep. 2019 Sep 5;21:100504. doi: 10.1016/j.ymgmr.2019.100504. eCollection 2019 Dec. Citation on PubMed
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