CHRDL1

protein-coding

chordin like 1, the group of Chordin family

Gene summary

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. [provided by RefSeq, Jan 2009]

Previous symbols:

MGC1

MANE transcript

NM_001143981.2

Inheritance

ClinVar variants

P:27U:114B:20

Top phenotype

Megalocornea 1, X-linked

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chrX:110,673,856-110,795,819

External References & Databases

Ensembl (ENSG00000101938)

Transcript & Mutation Effects

hg38 • Region Span ~122.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

isolated congenital megalocorneaSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010649

Submitter: Labcorp Genetics (formerly Invitae)

isolated congenital megalocorneaDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010649

Submitter: G2P

isolated congenital megalocorneaSUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010649

Submitter: Orphanet

Clinical Genomic Database (CGD)

Megalocornea 1, X-linkedXL

Manifestation: Ophthalmologic

Intervention: Ophthalmologic

Rationale: 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

Refs: 2571565; 22284829; 24073597; 25093588

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CHRDL1 variants in ClinVar

7 Conditions Cataloged

Inborn genetic diseasesTotal: 45

not providedTotal: 36

MegalocorneaTotal: 16

CHRDL1-related disorderTotal: 13

Isolated congenital megalocorneaTotal: 9

not specifiedTotal: 6

Corneal disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001143981.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			18 clinvar	7 clinvar	3 clinvar	28
missense	1 clinvar	2 clinvar	76 clinvar	4 clinvar	6 clinvar	89
nonsense	6 clinvar	6 clinvar	5 clinvar			17
start loss						0
frameshift	5 clinvar	2 clinvar				7
splice donor/acceptor (+/-2bp)	4 clinvar	1 clinvar	15 clinvar			20
Total	16	11	114	11	9	161

Highest pathogenic variant AF is 0.0000019921113

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001143981.2	RefSeq	NP_001137453.1	11	MANE Select
ENST00000372042.6	Ensembl	ENSP00000361112.1	11	MANE Select
NM_001143982.2	RefSeq	NP_001137454.1	11	Standard
NM_001143983.3	RefSeq	NP_001137455.2	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

ossification
eye development
nervous system development
cell differentiation
BMP signaling pathway

Cellular Component

extracellular region
endoplasmic reticulum lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372042
Coding exons: 11
Length: 122203
Individuals with no LoFs: 125727
Homozygous LoFs: 2
Heterozygous LoFs: 6
Defined: 125735
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.450	161	178	0.905	0.0000135	3012
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00011	0.000087	rare
Ashkenazi Jewish	0.00027	0.00020	rare
East Asian	0	0.0	absent
Finnish	0.000062	0.000046	rare
European (Non-Finnish)	0.000025	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.380

Intolerance Scores

LoFtool: 0.698
RVIS EVS: -0.01
RVIS percentile EVS: 53.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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