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CHRDL1 (Chordin-Like 1) is a gene that encodes a secreted protein known as Chordin-like protein 1. This protein plays a crucial role in embryonic development and has been associated with various biological processes in both development and disease.
	'''CHRDL1''' is a human protein-coding gene whose name stands for '''chordin like 1'''. It is located on the X chromosome at Xq23 and encodes a secreted protein involved in bone morphogenetic protein signalling.

== Gene and Protein Structure ==
The CHRDL1 gene is located on chromosome 3p25.3 and consists of 4 exons. Alternative splicing of the mRNA produces multiple isoforms of the Chordin-like protein 1.
	Older imported wording placed CHRDL1 on chromosome 3p25.3. That is not correct. Current NCBI records place CHRDL1 on Xq23.

The Chordin-like protein 1 is a member of the chordin family of proteins, which are secreted glycoproteins known for their roles in embryonic patterning and organogenesis. It contains several conserved structural domains, including von Willebrand factor type C domains, cysteine-rich repeat domains, and a chordin-like cysteine knot domain. These domains are involved in protein-protein interactions and are crucial for the protein's biological activity.
	== Gene and Protein ==
	CHRDL1 encodes chordin-like protein 1, also known in some sources as ventroptin. The protein is a bone morphogenetic protein antagonist, meaning it can bind BMP ligands and reduce their signalling activity.

== Function and Mechanism ==
Chordin-like protein 1 is primarily known for its role as a modulator of the bone morphogenetic protein (BMP) signaling pathway. The BMP pathway plays a key role in embryonic development, cell differentiation, and tissue homeostasis. Chordin-like protein 1 acts as an antagonist of BMP signaling by binding to BMP ligands and preventing their interaction with BMP receptors.
	NCBI lists CHRDL1 as a protein-coding gene on the X chromosome. The record also notes alternative transcript variants and aliases including CHL, MGC1, MGCN and VOPT.

Through its interaction with BMP ligands, Chordin-like protein 1 regulates the spatial and temporal distribution of BMP signals, thereby influencing cell fate determination, tissue differentiation, and morphogenesis during embryonic development. It helps establish concentration gradients of BMP signaling, which are critical for proper patterning of various tissues and organs.
	== Biological Role ==
	CHRDL1 is mainly discussed in relation to eye development. BMP signalling helps regulate tissue patterning during development, and CHRDL1 appears to contribute to normal development of the anterior segment of the eye.

In addition to its role in embryogenesis, CHRDL1 has been implicated in other biological processes. It has been shown to modulate angiogenesis, the process of forming new blood vessels, by interacting with vascular endothelial growth factor (VEGF) and regulating its signaling. CHRDL1 also plays a role in neural development and is involved in the regulation of axonal outgrowth and guidance.
	The gene has also been studied in retinal and neural development, but the strongest clinical link is with X-linked megalocornea.

== Clinical Significance ==	== Clinical Significance ==
Mutations or dysregulation of CHRDL1 have been associated with several human diseases and conditions. For instance, loss-of-function mutations in CHRDL1 have been linked to X-linked [[megalocornea]], a rare eye disorder characterized by an enlarged cornea. Megalocornea results from abnormal development of the eye during embryogenesis, and CHRDL1 is thought to play a role in this process.
	Pathogenic variants in CHRDL1 are associated with isolated congenital [[Megalocornea\|megalocornea]]. This condition involves enlarged corneas and a deep anterior chamber, usually without the raised intraocular pressure seen in congenital glaucoma.

Furthermore, altered expression of CHRDL1 has been observed in certain cancers, including breast cancer, gastric cancer, and colorectal cancer. Its dysregulation in these cancers suggests a potential involvement in tumor progression and metastasis. Studies have also suggested CHRDL1 as a potential therapeutic target for cancer treatment.
	Genomics England lists CHRDL1 on its corneal abnormalities panel for X-linked megalocornea. The inheritance pattern is X-linked, so males are more often affected, while carrier females may have no symptoms or milder findings.

	Complications of CHRDL1-related megalocornea can include lens instability, cataract, secondary glaucoma and other anterior-segment problems. The exact pattern varies by individual.

	== Diagnosis ==
	Diagnosis of CHRDL1-related disease is usually based on eye examination and genetic testing. Eye assessment may include corneal measurement, slit-lamp examination, refraction, eye-pressure measurement and imaging of the anterior chamber.

	Genetic testing can confirm CHRDL1 involvement when the clinical pattern suggests X-linked megalocornea.

	== Research ==
	Research has identified CHRDL1 variants in families with X-linked megalocornea and helped distinguish this condition from primary congenital glaucoma. Later studies have examined how CHRDL1 affects BMP signalling and eye development.

	Broader research has also examined CHRDL1 expression in cancers, but those findings should not be overstated on a general gene page unless tied to specific, sourced clinical claims.

	== See Also ==
	* [[Megalocornea]]
	* [[Genetic_Disorder]]
	* [[Ophthalmology]]

== References ==	== References ==
	* [https://www.ncbi.nlm.nih.gov/gtr/genes/91851/ NCBI Genetic Testing Registry: CHRDL1]
	* [https://panelapp.genomicsengland.co.uk/panels/250/gene/CHRDL1/ Genomics England PanelApp: CHRDL1]
	* [https://rarediseases.info.nih.gov/diseases/12648/isolated-congenital-megalocornea GARD: Isolated congenital megalocornea]
	* [https://pmc.ncbi.nlm.nih.gov/articles/PMC3276677/ X-linked megalocornea caused by mutations in CHRDL1]
	* [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104163 Association of CHRDL1 mutations and variants with X-linked megalocornea]

# Clark TG, Conway SJ, Scott IC. The Antagonistic Gene Paralogs Upregulated in Hypertrophic Hearts Encode Inhibitors of Wnt Signaling. J Biol Chem. 2015;290(8):4639-4651. doi:10.1074/jbc.M114.589073.
# Wotton KR, et al. Mutations in CELSR1 and CHRDL1 in patients with congenital cataracts and microcornea. JAMA Ophthalmol. 2014;132(8):1018-1023. doi:10.1001/jamaophthalmol.2014.893.
# Zhang B, Zhang B, Sun T. Chordin-like protein 1 promotes neuronal differentiation by inhibiting bone morphogenetic protein-4 in neural stem cells. Neuroscience. 2014;274:167-176. doi:10.1016/j.neuroscience.2014.05.026.
	[[Category:Genetics]]
	[[Category:Medicine]]
	[[Category:Ophthalmology]]