CHRDL1

Chr XXLR

chordin like 1

Also known as: CHL, MGC1, MGCN, NRLN1, VOPT, dA141H5.1

NCBI Gene: 91851ENSG00000101938UniProt: Q9BU40OMIM: 300350

This gene encodes an antagonist of bone morphogenetic protein 4 (BMP4) that regulates neural stem cell differentiation from gliogenesis to neurogenesis and plays a role in anterior segment eye development and retinal angiogenesis. Mutations cause X-linked recessive megalocornea 1, characterized by enlarged corneal diameter. The gene shows moderate constraint against loss-of-function variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.521 OMIM phenotype
Clinical Summary— CHRDL1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
93 unique Pathogenic / Likely Pathogenic· 57 VUS of 241 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.216
Z-score 3.13
OE 0.25 (0.13–0.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.45Z-score
OE missense 0.91 (0.80–1.03)
161 obs / 177.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.25 (0.13–0.52)
0≤0.351.4
Missense OE0.91 (0.80–1.03)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 5 / 20.2Missense obs/exp: 161 / 177.9Syn Z: -0.20
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCHRDL1-related megalocorneaLOFXLR
DN
0.6162th %ile
GOF
0.4874th %ile
LOF
0.4135th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

241 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic86
Likely Pathogenic7
VUS57
Likely Benign10
Benign13
Conflicting1
86
Pathogenic
7
Likely Pathogenic
57
VUS
10
Likely Benign
13
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
1
71
0
86
Likely Pathogenic
3
2
2
0
7
VUS
0
50
7
0
57
Likely Benign
0
3
1
6
10
Benign
0
6
3
4
13
Conflicting
—1
Total17628410174

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CHRDL1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients