CHRDL1

Chr XXLR

chordin like 1

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

NCBI Gene: 91851ENSG00000101938UniProt: Q9BU40

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]

Primary Disease Associations & Inheritance

Megalocornea 1, X-linkedMIM #309300
XLR
173
ClinVar variants
91
Pathogenic / LP
0.22
pLI score
0
Active trials
Clinical Summary— CHRDL1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
91 Pathogenic / Likely Pathogenic· 58 VUS of 173 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.45Z-score
OE missense 0.91 (0.80–1.03)
161 obs / 177.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.25 (0.13–0.52)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.80–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 5 / 20.2Missense obs/exp: 161 / 177.9Syn Z: -0.20

ClinVar Variant Classifications

173 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic85
Likely Pathogenic6
VUS58
Likely Benign10
Benign13
Conflicting1
85
Pathogenic
6
Likely Pathogenic
58
VUS
10
Likely Benign
13
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
1
77
0
85
Likely Pathogenic
0
2
4
0
6
VUS
0
50
8
0
58
Likely Benign
0
3
1
6
10
Benign
0
6
3
4
13
Conflicting
—1
Total7629310173

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.

Gene2Phenotype Curations

CHRDL1-related megalocornea

definitive
Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
CHORDIN-LIKE 1; CHRDL1
MIM #300350 · *

Megalocornea 1, X-linked

MIM #309300

Molecular basis of disorder known

X-linked recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Association of CHRDL1 mutations and variants with X-linked megalocornea, Neuhäuser syndrome and central corneal thickness.
Davidson AE et al.·PLoS One
2014
Effect of CHRDL1 on angiogenesis and metastasis of colorectal cancer cells via TGF-β/VEGF pathway.
Li J et al.·Mol Carcinog
2024
CHRDL1, NEFH, TAGLN and SYNM as novel diagnostic biomarkers of benign prostatic hyperplasia and prostate cancer.
Su Z et al.·Cancer Biomark
2023
Context-dependent tumor-suppressive BMP signaling in diffuse intrinsic pontine glioma regulates stemness through epigenetic regulation of CXXC5.
Sun Y et al.·Nat Cancer
2022
Molecular mechanism of CHRDL1-mediated X-linked megalocornea in humans and in Xenopus model.
Pfirrmann T et al.·Hum Mol Genet
2015Case report
CHRDL1 Regulates Stemness in Glioma Stem-like Cells.
Berglar I et al.·Cells
2022
CHRDL1 inhibits OSCC metastasis via MAPK signaling-mediated inhibition of MED29.
Huang S et al.·Mol Med
2024
Novel CHRDL1 mutation causing X-linked megalocornea in a family with mild anterior segment manifestations in carrier females.
Arce-Gonzalez R et al.·Ophthalmic Genet
2022Case report
RUNX2 Regulates Osteoblast Differentiation via the BMP4 Signaling Pathway.
Liu DD et al.·J Dent Res
2022
The unique role of bone marrow adipose tissue in ovariectomy-induced bone loss in mice.
Li J et al.·Endocrine
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools