Chordin-like_1

Chordin-like 1

Chordin-like 1

Protein-coding gene in humans

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]

Quick Facts CHRDL1, Identifiers ...

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.

Clinical significance

Mutations in CHRDL1 are associated to Neuhäuser Syndrome, X-linked megalocornea and central corneal thickness.[10]

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 reduced plasticity.[9]

References

  1. [1]
    GRCh38: Ensembl release 89: ENSG00000101938 – Ensembl, May 2017
  2. [2]
    GRCm38: Ensembl release 89: ENSMUSG00000031283 – Ensembl, May 2017
  3. [3]
    "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. [4]
    "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. [5]
    "Entrez Gene: Chordin-like 1". Retrieved 2014-08-06.
  6. [6]
    Pfirrmann T, Emmerich D, Ruokonen P, Quandt D, Buchen R, Fischer-Zirnsak B, et al. (June 2015). "Molecular mechanism of CHRDL1-mediated X-linked megalocornea in humans and in Xenopus model". Human Molecular Genetics. 24 (11): 3119–32. doi:10.1093/hmg/ddv063. PMID 25712132.
  7. [7]
    Liu T, Li B, Zheng XF, Jiang SD, Zhou ZZ, Xu WN, et al. (2019). "Chordin-Like 1 Improves Osteogenesis of Bone Marrow Mesenchymal Stem Cells Through Enhancing BMP4-SMAD Pathway". Frontiers in Endocrinology. 10: 360. doi:10.3389/fendo.2019.00360. PMC 6582276. PMID 31249554.
  8. [8]
    Pei YF, Zhang YJ, Lei Y, Wu WD, Ma TH, Liu XQ (April 2017). "Hypermethylation of the CHRDL1 promoter induces proliferation and metastasis by activating Akt and Erk in gastric cancer". Oncotarget. 8 (14): 23155–23166. doi:10.18632/oncotarget.15513. PMC 5410293. PMID 28423564.
  9. [9]
    Blanco-Suarez E, Liu TF, Kopelevich A, Allen NJ (December 2018). "Astrocyte-Secreted Chordin-like 1 Drives Synapse Maturation and Limits Plasticity by Increasing Synaptic GluA2 AMPA Receptors". Neuron. 100 (5): 1116–1132.e13. doi:10.1016/j.neuron.2018.09.043. PMC 6382071. PMID 30344043.
  10. [10]
    Davidson AE, Cheong SS, Hysi PG, Venturini C, Plagnol V, Ruddle JB, et al. (2014). "Association of CHRDL1 mutations and variants with X-linked megalocornea, Neuhäuser syndrome and central corneal thickness". PLOS ONE. 9 (8): e104163. Bibcode:2014PLoSO...9j4163D. doi:10.1371/journal.pone.0104163. PMC 4122416. PMID 25093588.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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