Chordin-like 1 is a protein that in humans is encoded by the CHRDL1 gene.[5] Chordin-Like 1 (CHRDL1) is a structural glycoprotein that sits on the X chromosome and specifically encodes Venotropin, which is an antagonistic protein to bone morphogenic protein 4.[6]
Function
This gene encodes an antagonist of bone morphogenetic protein 4. The encoded protein may play a role in topographic retinotectal projection and in the regulation of retinal angiogenesis in response to hypoxia. Alternatively spliced transcript variants encoding different isoforms have been described.[5]
CHRDL1 plays important roles in processes such as embryonic cell differentiation, osteogenesis, neurogenesis, tumor and metastasis suppression, and retinal formation.[7][8] The highest expression of this gene is found in the anterior eye segment and retina as well as in the cerebellum and neocortex.[6] In the neocortex, it peaks at the time of synapse maturation to allow for proper synaptic formation.[9] Therefore, this gene is important in proper formation of the central nervous system and the eyes.
Mutations in this gene may cause a variety of effects on the aforementioned processes. One potential outcome of a CHRDL1 mutation is non-syndromic X-linked megalocornea (XMC) that results from either a missense, nonsense, or frameshift mutation of the gene.[6] XMC is an enlargement of the anterior segments of the eye that may lead to other issues such as cataracts and glaucoma.[6] Another potential outcome is carcinogenic formation. Since CHRDL1 is a tumor and metastasis suppressor, a mutation in this gene may lead to tumor cell formation.[8] The most major effect a mutation could have is on synaptic stabilization. Since the gene limits synaptic plasticity, a mutation may cause issues in proper synapse maturation, leading to a variety of neurological disorders.[9] There is currently a knockout model for this gene that shows disruption may cause altered synaptic events and reduced synaptic GluA2 AMPARs leading to increased plasticity.[9]
Sakuta H, Suzuki R, Takahashi H, Kato A, Shintani T, Yamamoto TS, et al. (July 2001). "Ventroptin: a BMP-4 antagonist expressed in a double-gradient pattern in the retina". Science. 293 (5527): 111–5. doi:10.1126/science.1058379. PMID11441185. S2CID32368073.
Fernandes H, Dechering K, van Someren E, Steeghs I, Apotheker M, Mentink A, et al. (2010). "Effect of chordin-like 1 on MC3T3-E1 and human mesenchymal stem cells". Cells Tissues Organs. 191 (6): 443–52. doi:10.1159/000281825. PMID20130390. S2CID39732221.
Coffinier C, Tran U, Larraín J, De Robertis EM (January 2001). "Neuralin-1 is a novel Chordin-related molecule expressed in the mouse neural plate". Mechanisms of Development. 100 (1): 119–22. doi:10.1016/s0925-4773(00)00507-4. PMID11118896.
