Chordin-like 1

CHRDL1
Identifiers
Aliases	CHRDL1, chordin-like 1, CHL, MGC1, MGCN, NRLN1, VOPT, dA141H5.1, chordin like 1
External IDs	OMIM: 300350 MGI: 1933172 HomoloGene: 12834 GeneCards: CHRDL1
Gene location (Human) Chr. X chromosome (human) Band Xq23 Start 110,673,856 bp End 110,795,819 bp
Gene location (Mouse) Chr. X chromosome (mouse) Band X|X F2 Start 142,068,670 bp End 142,177,258 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in vena cava parietal pleura saphenous vein urethra pericardium germinal epithelium seminal vesicula gastric mucosa synovial joint olfactory bulb Top expressed in sciatic nerve white adipose tissue ciliary body iris intercostal muscle carotid body subcutaneous adipose tissue seminal vesicula stria vascularis ankle More reference expression data BioGPS n/a
Orthologs Species Human Mouse Entrez 91851 83453 Ensembl ENSG00000101938 ENSMUSG00000031283 UniProt Q9BU40 Q920C1 RefSeq (mRNA) NM_001143981 NM_001143982 NM_001143983 NM_145234 NM_001114385 NM_031258 NM_001358592 RefSeq (protein) NP_001137453 NP_001137454 NP_001137455 NP_660277 NP_001354133 NP_001354134 NP_001354135 NP_001354136 NP_001354137 NP_001354138 NP_001107857 NP_112548 NP_001345521 Location (UCSC) Chr X: 110.67 – 110.8 Mb Chr X: 142.07 – 142.18 Mb PubMed search
Wikidata
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Chordin-like 1 is a protein that in humans is encoded by the CHRDL1 gene. 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.

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.

CHRDL1 plays important roles in processes such as embryonic cell differentiation, osteogenesis, neurogenesis, tumor and metastasis suppression, and retinal formation. The highest expression of this gene is found in the anterior eye segment and retina as well as in the cerebellum and neocortex. In the neocortex, it peaks at the time of synapse maturation to allow for proper synaptic formation. 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.

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. XMC is an enlargement of the anterior segments of the eye that may lead to other issues such as cataracts and glaucoma. 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. 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. 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.

Further reading

• 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. PMID 11441185. S2CID 32368073.
• Webb TR, Matarin M, Gardner JC, Kelberman D, Hassan H, Ang W, et al. (February 2012). "X-linked megalocornea caused by mutations in CHRDL1 identifies an essential role for ventroptin in anterior segment development". American Journal of Human Genetics. 90 (2): 247–59. doi:10.1016/j.ajhg.2011.12.019. PMC 3276677. PMID 22284829.
• Kane R, Godson C, O'Brien C (June 2008). "Chordin-like 1, a bone morphogenetic protein-4 antagonist, is upregulated by hypoxia in human retinal pericytes and plays a role in regulating angiogenesis". Molecular Vision. 14: 1138–48. PMC 2435163. PMID 18587495.
• 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. PMID 20130390. S2CID 39732221.
• Coronary Artery Disease (C4D) Genetics Consortium (March 2011). "A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease". Nature Genetics. 43 (4): 339–44. doi:10.1038/ng.782. PMID 21378988. S2CID 39712343.{{cite journal}}: CS1 maint: numeric names: authors list (link)
• Larman BW, Karolak MJ, Adams DC, Oxburgh L (May 2009). "Chordin-like 1 and twisted gastrulation 1 regulate BMP signaling following kidney injury". Journal of the American Society of Nephrology. 20 (5): 1020–31. doi:10.1681/ASN.2008070768. PMC 2678041. PMID 19357253.
• 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. PMID 11118896.
• Gazzerro E, Canalis E (June 2006). "Bone morphogenetic proteins and their antagonists". Reviews in Endocrine & Metabolic Disorders. 7 (1–2): 51–65. doi:10.1007/s11154-006-9000-6. PMID 17029022. S2CID 20907947.
• Chen D, Zhao M, Mundy GR (December 2004). "Bone morphogenetic proteins". Growth Factors. 22 (4): 233–41. doi:10.1080/08977190412331279890. PMID 15621726. S2CID 22932278.

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