Isolated congenital megalocornea

Summary

Isolated congenital megalocornea (MONDO:0010649) is a disease caused by CHRDL1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CHRDL1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated congenital megalocornea
Mondo ID	MONDO:0010649
OMIM	309300
Orphanet	91489
SNOMED CT	734026006
UMLS	C4518341
MedGen	1385311
GARD	0012648
Is cancer (heuristic)	no

Also known as: congenital anterior megalophthalmia · isolated congenital megalocornea · megalocornea · megalocornea 1, X-linked, X-linked recessive · MGC1

Data availability: 5 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › corneal disorder › megalocornea › isolated congenital megalocornea

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

2 pathogenic, 2 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1299397	NM_001143981.2(CHRDL1):c.207+1G>A	CHRDL1	Pathogenic	no assertion criteria provided
3629459	NM_001143981.2(CHRDL1):c.349G>T (p.Glu117Ter)	CHRDL1	Pathogenic	criteria provided, single submitter
1698959	NM_001143981.2(CHRDL1):c.872G>A (p.Cys291Tyr)	CHRDL1	Likely pathogenic	criteria provided, single submitter
4813646	NM_001143981.2(CHRDL1):c.87dup (p.Val30fs)	CHRDL1	Likely pathogenic	criteria provided, single submitter
4072308	NM_001143981.2(CHRDL1):c.541+3A>G	CHRDL1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CHRDL1	Definitive	X-linked	isolated congenital megalocornea	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CHRDL1	Orphanet:91489	Isolated congenital megalocornea

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CHRDL1	HGNC:29861	ENSG00000101938	Q9BU40	Chordin-like protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CHRDL1	Chordin-like protein 1	Antagonizes the function of BMP4 by binding to it and preventing its interaction with receptors.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CHRDL1	Other/Unknown	no		VWF_dom, CHRDL_1/2_C, CHRDL1/2

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
decidua	1
parietal pleura	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CHRDL1	255	broad	marker	decidua, vena cava, parietal pleura

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CHRDL1	1,294

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CHRDL1	Q9BU40	69.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by BMP	1	356.9×	0.008	CHRDL1
Post-translational protein phosphorylation	1	100.2×	0.012	CHRDL1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.012	CHRDL1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
AMPA glutamate receptor clustering	1	3370.4×	0.002	CHRDL1
embryonic axis specification	1	2407.4×	0.002	CHRDL1
excitatory chemical synaptic transmission	1	1296.3×	0.003	CHRDL1
synapse maturation	1	936.2×	0.003	CHRDL1
eye development	1	351.1×	0.005	CHRDL1
negative regulation of BMP signaling pathway	1	290.6×	0.005	CHRDL1
regulation of synaptic plasticity	1	259.3×	0.005	CHRDL1
ossification	1	227.7×	0.005	CHRDL1
BMP signaling pathway	1	200.6×	0.006	CHRDL1
cell differentiation	1	29.1×	0.034	CHRDL1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHRDL1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CHRDL1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CHRDL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.