CHRDL1

chordin like 1, the group of Chordin family

Basic information

Region (hg38): X:110673856-110795819

Previous symbols: [ "MGC1" ]

Links

ENSG00000101938 ∙ NCBI:91851 ∙ OMIM:300350 ∙ HGNC:29861 ∙ Uniprot:Q9BU40 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• isolated congenital megalocornea (Definitive), mode of inheritance: XLR
• isolated congenital megalocornea (Strong), mode of inheritance: XL
• isolated congenital megalocornea (Supportive), mode of inheritance: XL
• isolated congenital megalocornea (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Megalocornea 1, X-linked	XL	Ophthalmologic	Individuals may be at risk for manifestations such as cataract development and glaucoma after lenticular dislocation or subluxation, and awareness may allow early management of sequelae	Ophthalmologic	2571565; 22284829; 24073597; 25093588

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHRDL1 gene.

• Megalocornea (7 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHRDL1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	5	9
missense		2	15	1	3	21
nonsense	3					3
start loss			1	1		2
frameshift	2					2
inframe indel						0
splice donor/acceptor (+/-2bp)	3					3
splice region		1				1
non coding					2	2
Total	8	2	16	6	10

Highest pathogenic variant AF is 0.00000895

Variants in CHRDL1

This is a list of pathogenic ClinVar variants found in the CHRDL1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-110676263-A-G			Benign (Dec 11, 2023)
X-110676335-C-T		Inborn genetic diseases	Uncertain significance (Jun 01, 2023)
X-110676338-C-T		Inborn genetic diseases	Uncertain significance (Feb 21, 2024)
X-110679410-A-G			Uncertain significance (Feb 01, 2024)
X-110681481-C-A		Megalocornea	Pathogenic (-)
X-110681487-C-T			Benign (Sep 19, 2023)
X-110681515-G-A		Megalocornea	Pathogenic (May 02, 2021)
X-110681595-G-A		Inborn genetic diseases	Uncertain significance (Nov 10, 2022)
X-110681668-T-C			Benign (Nov 17, 2022)
X-110688606-T-A		Megalocornea	Pathogenic (-)
X-110688614-C-A		Megalocornea	Uncertain significance (-)
X-110688628-T-C		not specified	Benign (Jan 30, 2024)
X-110688641-T-C		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
X-110688653-T-A			Uncertain significance (Sep 01, 2023)
X-110688673-G-A			Benign (Oct 11, 2023)
X-110688709-AC-A		Megalocornea	Pathogenic (Feb 10, 2012)
X-110688710-C-T		Isolated congenital megalocornea	Likely pathogenic (Feb 02, 2022)
X-110688773-TGA-T		Megalocornea	Pathogenic (Jun 01, 2015)
X-110688800-C-A		Megalocornea	Pathogenic (Feb 10, 2012)
X-110694143-A-T			Benign (May 02, 2023)
X-110694190-T-C			Uncertain significance (Jun 12, 2022)
X-110694206-G-A			Likely benign (Jan 04, 2024)
X-110694255-G-A		Inborn genetic diseases	Uncertain significance (Mar 21, 2022)
X-110694289-G-A		Megalocornea	Pathogenic (Feb 10, 2012)
X-110694308-G-A			Likely benign (Nov 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHRDL1	protein_coding	protein_coding	ENST00000372042	11	122203

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.216	0.783	125727	2	6	125735	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.450	161	178	0.905	0.0000135	3012
Missense in Polyphen		71	74.837	0.94873		1222
Synonymous	-0.199	65	63.0	1.03	0.00000480	834
Loss of Function	3.13	5	20.2	0.248	0.00000161	327

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000110	0.000110
Ashkenazi Jewish	0.000274	0.000198
East Asian	0.00	0.00
Finnish	0.0000625	0.0000462
European (Non-Finnish)	0.0000250	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Antagonizes the function of BMP4 by binding to it and preventing its interaction with receptors. Alters the fate commitment of neural stem cells from gliogenesis to neurogenesis. Contributes to neuronal differentiation of neural stem cells in the brain by preventing the adoption of a glial fate. May play a crucial role in dorsoventral axis formation. May play a role in embryonic bone formation (By similarity). May also play an important role in regulating retinal angiogenesis through modulation of BMP4 actions in endothelial cells. Plays a role during anterior segment eye development. {ECO:0000250, ECO:0000269|PubMed:18587495, ECO:0000269|PubMed:22284829}.
• Disease: DISEASE: Megalocornea 1, X-linked (MGC1) [MIM:309300]: An eye disorder in which the corneal diameter is bilaterally enlarged (greater than 13 mm) without an increase in intraocular pressure. It may also be referred to as anterior megalophthalmos, since the entire anterior segment is larger than normal. Features of megalocornea in addition to a deep anterior chamber include astigmatic refractive errors, atrophy of the iris stroma, miosis secondary to decreased function of the dilator muscle, iridodonesis, and tremulousness, subluxation, or dislocation of the lens. Whereas most affected individuals exhibit normal ocular function, complications include cataract development and glaucoma following lenticular dislocation or subluxation. {ECO:0000269|PubMed:22284829}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signal Transduction;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);BMP receptor signaling;BMP Signalling Pathway;Signaling by BMP;Signaling by TGF-beta family members (Consensus)

Recessive Scores

• pRec: 0.380

Intolerance Scores

• loftool: 0.698
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.51

Haploinsufficiency Scores

• pHI: 0.407
• hipred: Y
• hipred_score: 0.528
• ghis: 0.524

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Chrdl1

Gene ontology

• Biological process: ossification;eye development;nervous system development;cell differentiation;BMP signaling pathway;negative regulation of BMP signaling pathway;post-translational protein modification;cellular protein metabolic process;compound eye development
• Cellular component: extracellular region;endoplasmic reticulum lumen