CHRDL1

Summary

CHRDL1 (chordin like 1, HGNC:29861) is a protein-coding gene on chromosome Xq23, encoding Chordin-like protein 1 (Q9BU40). Antagonizes the function of BMP4 by binding to it and preventing its interaction with receptors. It is haploinsufficient (ClinGen: sufficient evidence).

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.

Source: NCBI Gene 91851 — RefSeq curated summary.

At a glance

• Gene–disease (curated): isolated congenital megalocornea (Definitive, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 168 total — 18 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 16
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001143981

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29861
Approved symbol	CHRDL1
Name	chordin like 1
Location	Xq23
Locus type	gene with protein product
Status	Approved
Aliases	NRLN1, CHL
Ensembl gene	ENSG00000101938
Ensembl biotype	protein_coding
OMIM	300350
Entrez	91851

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 18 protein_coding

ENST00000372042, ENST00000372045, ENST00000394797, ENST00000444321, ENST00000482160, ENST00000881324, ENST00000881325, ENST00000881326, ENST00000881327, ENST00000881328, ENST00000881329, ENST00000881330, ENST00000881331, ENST00000932200, ENST00000932201, ENST00000944292, ENST00000944293, ENST00000944294

RefSeq mRNA: 10 — MANE Select: NM_001143981 NM_001143981, NM_001143982, NM_001143983, NM_001367204, NM_001367205, NM_001367206, NM_001367207, NM_001367208, NM_001367209, NM_145234

CCDS: CCDS14553, CCDS48148, CCDS48149, CCDS48150

Canonical transcript exons

ENST00000372042 — 12 exons

Exon	Start	End
ENSE00000674779	110679336	110679425
ENSE00000674786	110688594	110688803
ENSE00000674788	110694163	110694331
ENSE00001033846	110759661	110759754
ENSE00001033853	110792088	110792215
ENSE00001033855	110762695	110762807
ENSE00001159496	110700654	110700721
ENSE00001159500	110719835	110719928
ENSE00001456765	110681482	110681649
ENSE00001456766	110721385	110721530
ENSE00001456767	110795744	110795817
ENSE00001456774	110673856	110676361

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.53.

FANTOM5 (CAGE): breadth broad, TPM avg 10.5395 / max 550.9912, expressed in 620 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200158	9.7498	595
200157	0.3105	161
200156	0.1924	102
200159	0.1676	88
200160	0.0730	31
200155	0.0462	22

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	99.53	gold quality
vena cava	UBERON:0004087	99.41	gold quality
parietal pleura	UBERON:0002400	99.32	gold quality
saphenous vein	UBERON:0007318	99.22	gold quality
urethra	UBERON:0000057	99.02	gold quality
pericardium	UBERON:0002407	99.00	gold quality
germinal epithelium of ovary	UBERON:0001304	98.33	gold quality
seminal vesicle	UBERON:0000998	98.30	gold quality
mucosa of stomach	UBERON:0001199	98.14	gold quality
skin of hip	UBERON:0001554	98.14	gold quality
synovial joint	UBERON:0002217	97.70	gold quality
olfactory bulb	UBERON:0002264	97.63	gold quality
right lung	UBERON:0002167	97.52	gold quality
dorsal root ganglion	UBERON:0000044	97.51	gold quality
superficial temporal artery	UBERON:0001614	97.41	gold quality
pleura	UBERON:0000977	97.39	gold quality
mammary duct	UBERON:0001765	97.38	gold quality
adipose tissue	UBERON:0001013	97.23	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.62	gold quality
cauda epididymis	UBERON:0004360	96.62	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.62	gold quality
peritoneum	UBERON:0002358	96.46	gold quality
omental fat pad	UBERON:0010414	96.46	gold quality
ganglionic eminence	UBERON:0004023	96.44	gold quality
tibial nerve	UBERON:0001323	96.34	gold quality
connective tissue	UBERON:0002384	96.32	gold quality
penis	UBERON:0000989	96.25	gold quality
myometrium	UBERON:0001296	96.18	gold quality
body of uterus	UBERON:0009853	96.06	gold quality
thoracic mammary gland	UBERON:0005200	95.98	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-23	yes	3070.75
E-MTAB-8142	yes	40.20
E-ANND-3	yes	20.55
E-HCAD-4	yes	17.16
E-MTAB-9543	yes	12.20
E-GEOD-130148	yes	5.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

151 targeting CHRDL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 13)

• reports the cloning of chick ventroptin and its importance in topographic retinotectal projection (PMID:11441185)
• Hypoxia-induced upregulation of CHL-1 alters the homeostatic balance between BMP-4 and VEGF to synergize with VEGF in driving retinal angiogenesis. (PMID:18587495)
• CHRDL1 is expressed in the developing human cornea and anterior segment in addition to the retina. (PMID:22284829)
• We provide the initial confirmation that X-linked megalocornea is associated with mutations in the CHRDL1 gene. (PMID:24073597)
• Novel CHRDL1 mutations in ten families with X-linked megalocornea, are reported. (PMID:25093588)
• CHRDL1 plays a key role in cornea homeostasis as evidenced by disease causing mutations in X-linked megalocornea. (PMID:25712132)
• The detection of mutations in the CHRDL1 gene is useful for differential diagnosis with different forms of megalocornea. (PMID:26020825)
• These studies have identified and validated new factors enriched in juvenile chondrocytes as compared to adult chondrocytes including secreted extracellular matrix factors chordin-like 1 (CHRDL1) and microfibrillar-associated protein 4 (MFAP4). (PMID:26955889)
• Results show that Chrdl1 expression is upregulated in numerous breast cancer cells following TGF-beta stimulation and demonstrated that Chrdl1 acts as an inhibitor of BMP4-induced migration and invasion. (PMID:26976638)
• Finally, in vivo experiments confirmed that CHRDL1 acted as a tumor suppressor gene in suppressing tumor growth and metastasis (PMID:28423564)
• Study on the expression and function of chordin-like 1 in oral squamous cell carcinoma. (PMID:35510812)
• Bioinformatics identify the role of chordin-like 1 in thyroid cancer. (PMID:36749222)
• CHRDL1 inhibits OSCC metastasis via MAPK signaling-mediated inhibition of MED29. (PMID:39462350)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Chrdl1	ENSMUSG00000031283
rattus_norvegicus	Chrdl1	ENSRNOG00000004330

Paralogs (19): CHRDL2 (ENSG00000054938), CHRD (ENSG00000090539), TECTA (ENSG00000109927), VWF (ENSG00000110799), MUC5B (ENSG00000117983), KCP (ENSG00000135253), ZAN (ENSG00000146839), CRIM1 (ENSG00000150938), BMPER (ENSG00000164619), OTOGL (ENSG00000165899), VWCE (ENSG00000167992), VWC2L (ENSG00000174453), MUC6 (ENSG00000184956), OTOG (ENSG00000188162), VWC2 (ENSG00000188730), MUC2 (ENSG00000198788), MUC19 (ENSG00000205592), MUC5AC (ENSG00000215182), FCGBP (ENSG00000275395)

Protein

Protein identifiers

Chordin-like protein 1 — Q9BU40 (reviewed: Q9BU40)

Alternative names: Neuralin-1, Neurogenesin-1, Ventroptin

All UniProt accessions (2): Q9BU40, A0A452Q6Z9

UniProt curated annotations — full annotation on UniProt →

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. 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.

Subcellular location. Secreted.

Tissue specificity. Expressed in the developing cornea and in the eye anterior segment in addition to the retina. Differentially expressed in the fetal brain. There is high expression in cerebellum and neocortex. Expressed in retinal pericytes.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Induction. By hypoxia in retinal pericytes.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BU40-6	1	yes
Q9BU40-3	2
Q9BU40-4	3
Q9BU40-5	4

RefSeq proteins (10): NP_001137453, NP_001137454, NP_001137455, NP_001354133, NP_001354134, NP_001354135, NP_001354136, NP_001354137, NP_001354138, NP_660277 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001007	VWF_dom	Domain
IPR045716	CHRDL_1/2_C	Domain
IPR045717	CHRDL1/2	Family

Pfam: PF00093, PF19548, PF23334

UniProt features (13 total): splice variant 3, domain 3, glycosylation site 2, signal peptide 1, chain 1, sequence variant 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BU40-F1	69.79	0.13

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (2): 118, 291

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-201451	Signaling by BMP
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275	Post-translational protein phosphorylation

MSigDB gene sets: 266 (showing top): LI_CISPLATIN_RESISTANCE_DN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, LEE_NEURAL_CREST_STEM_CELL_DN, WALLACE_PROSTATE_CANCER_RACE_UP, BENPORATH_ES_WITH_H3K27ME3, GOBP_AXIS_SPECIFICATION, HNF3ALPHA_Q6, GOBP_EMBRYONIC_AXIS_SPECIFICATION, RORA1_01, LI_WILMS_TUMOR, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, SCHLESINGER_METHYLATED_DE_NOVO_IN_CANCER, GGGTGGRR_PAX4_03, GOBP_CELL_CELL_SIGNALING, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN

GO Biological Process (12): embryonic axis specification (GO:0000578), ossification (GO:0001503), eye development (GO:0001654), cell differentiation (GO:0030154), BMP signaling pathway (GO:0030509), negative regulation of BMP signaling pathway (GO:0030514), regulation of synaptic plasticity (GO:0048167), synapse maturation (GO:0060074), AMPA glutamate receptor clustering (GO:0097113), excitatory chemical synaptic transmission (GO:0098976), nervous system development (GO:0007399), system development (GO:0048731)

GO Molecular Function (3): BMP binding (GO:0036122), transforming growth factor beta binding (GO:0050431), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788), plasma membrane (GO:0005886), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by TGFB family members	1
Metabolism of proteins	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytokine binding	2
axis specification	1
embryonic pattern specification	1
multicellular organismal process	1
sensory organ development	1
visual system development	1
cellular developmental process	1
cellular response to BMP stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
nervous system development	1
developmental maturation	1
synapse organization	1
postsynaptic membrane organization	1
glutamate receptor clustering	1
chemical synaptic transmission	1
excitatory postsynaptic potential	1
system development	1
multicellular organism development	1
anatomical structure development	1
growth factor binding	1
binding	1
cellular anatomical structure	1
endoplasmic reticulum	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
cell junction	1

Protein interactions and networks

STRING

1274 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRDL1	BMP4	P12644	545
CHRDL1	GREM2	Q9H772	544
CHRDL1	NOG	Q13253	494
CHRDL1	WFS1	O76024	477
CHRDL1	CCN1	O00622	463
CHRDL1	FSTL3	O95633	447
CHRDL1	GJA1	P17302	444
CHRDL1	GREM1	O60565	437
CHRDL1	SOST	Q9BQB4	433
CHRDL1	ATP1A2	P50993	429
CHRDL1	FSTL5	Q8N475	418
CHRDL1	MFAP4	P55083	416
CHRDL1	SPARCL1	Q14515	398
CHRDL1	RTL9	Q8NET4	392
CHRDL1	IRAG1	Q9Y6F6	388

IntAct

6 interactions, top by confidence:

A	B	Type	Score
CHRDL1	ZZEF1	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
PARP2	CHRDL1	psi-mi:“MI:0557”(adp ribosylation reaction)	0.440
rpoB	CHRDL1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): CALCOCO2 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS), HECTD3 (Affinity Capture-MS), LRP1B (Affinity Capture-MS), SNX27 (Affinity Capture-MS), CHRDL1 (Proximity Label-MS), CHRDL1 (Two-hybrid), LRP1B (Affinity Capture-MS), HECTD3 (Affinity Capture-MS), UBR1 (Affinity Capture-MS), CALCOCO2 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS)

ESM2 similar proteins: A4IIA2, A5A6L1, B3F211, O00622, O35251, O43915, O61307, O93525, P01127, P08833, P12843, P15473, P16612, P18406, P21743, P24591, P24593, P24594, P31240, P47876, P47877, P49011, Q05717, Q06481, Q07079, Q28985, Q29400, Q5XHC5, Q66K08, Q6Q484, Q6Q7I7, Q76LD0, Q8BLY1, Q8CD91, Q90WV8, Q90ZD5, Q920C1, Q95229, Q99PS1, Q9BU40

Diamond homologs: A0A1D5NSM8, A1A5Y0, A2AVA0, A2RUV0, A2VCU8, A5A8Y8, A6QR11, B3EWY9, B5DFC9, G3I6Z6, O75095, O88322, P07996, P0C6B8, P10493, P12105, P14585, P21783, P35441, P35448, P35555, P35556, P41990, P46531, P82279, P98133, Q01705, Q07008, Q14112, Q20911, Q28178, Q2PC93, Q2TAL6, Q2VWQ2, Q3U515, Q4LDE5, Q5R3Z7, Q5RBP1, Q61220, Q61554

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — LGGNOS.

Clinical variants and AI predictions

ClinVar

168 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	5
Uncertain significance	52
Likely benign	8
Benign	14

Top pathogenic / likely-pathogenic (23)

Variant ID	HGVS	Classification
1065523	NM_001143981.2(CHRDL1):c.1123C>T (p.Gln375Ter)	Pathogenic
1076999	NM_001143981.2(CHRDL1):c.976A>T (p.Lys326Ter)	Pathogenic
1077000	NM_001143981.2(CHRDL1):c.94+1G>A	Pathogenic
1077001	NM_001143981.2(CHRDL1):c.1156+1G>T	Pathogenic
1077004	NM_001143981.2(CHRDL1):c.483dup (p.Lys162fs)	Pathogenic
1077007	NM_001143981.2(CHRDL1):c.229C>T (p.Arg77Ter)	Pathogenic
1299397	NM_001143981.2(CHRDL1):c.207+1G>A	Pathogenic
2018090	NM_001143981.2(CHRDL1):c.145A>T (p.Arg49Ter)	Pathogenic
218164	NM_001143981.2(CHRDL1):c.807_808del (p.His270fs)	Pathogenic
2423879	NC_000023.10:g.(?110005903)(110006055_?)del	Pathogenic
29957	NM_001143981.2(CHRDL1):c.872del (p.Cys291fs)	Pathogenic
29958	NM_001143981.2(CHRDL1):c.782G>T (p.Cys261Phe)	Pathogenic
29959	NM_001143981.2(CHRDL1):c.301+2T>G	Pathogenic
29960	NM_001143981.2(CHRDL1):c.102_103del (p.Glu34fs)	Pathogenic
29961	NM_001143981.2(CHRDL1):c.652C>T (p.Arg218Ter)	Pathogenic
3629459	NM_001143981.2(CHRDL1):c.349G>T (p.Glu117Ter)	Pathogenic
3648102	NM_001143981.2(CHRDL1):c.311T>A (p.Leu104Ter)	Pathogenic
369678	NM_001143981.2(CHRDL1):c.520dup (p.Ser174fs)	Pathogenic
1077002	NM_001143981.2(CHRDL1):c.436T>G (p.Cys146Gly)	Likely pathogenic
1698959	NM_001143981.2(CHRDL1):c.872G>A (p.Cys291Tyr)	Likely pathogenic
3573702	NM_001143981.2(CHRDL1):c.446C>A (p.Ser149Ter)	Likely pathogenic
4072107	NM_001143981.2(CHRDL1):c.176T>A (p.Leu59Ter)	Likely pathogenic
4813646	NM_001143981.2(CHRDL1):c.87dup (p.Val30fs)	Likely pathogenic

SpliceAI

2060 predictions. Top by Δscore:

Variant	Effect	Δscore
X:110679332:TTACT:T	donor_loss	1.0000
X:110679333:TACTC:T	donor_loss	1.0000
X:110679334:A:AC	donor_gain	1.0000
X:110679334:A:C	donor_loss	1.0000
X:110679334:ACT:A	donor_gain	1.0000
X:110679335:C:CA	donor_gain	1.0000
X:110679335:CT:C	donor_gain	1.0000
X:110679335:CTC:C	donor_gain	1.0000
X:110679335:CTCA:C	donor_gain	1.0000
X:110679335:CTCAG:C	donor_gain	1.0000
X:110679423:TGC:T	acceptor_gain	1.0000
X:110679433:C:CT	acceptor_gain	1.0000
X:110681480:AC:A	donor_gain	1.0000
X:110681481:CC:C	donor_gain	1.0000
X:110681657:C:CT	acceptor_gain	1.0000
X:110681658:A:T	acceptor_gain	1.0000
X:110688800:CACA:C	acceptor_gain	1.0000
X:110688801:ACA:A	acceptor_gain	1.0000
X:110688802:CA:C	acceptor_gain	1.0000
X:110688802:CAC:C	acceptor_gain	1.0000
X:110688804:C:CC	acceptor_gain	1.0000
X:110694157:CCTTA:C	donor_loss	1.0000
X:110694158:CTTA:C	donor_loss	1.0000
X:110694159:TTAC:T	donor_loss	1.0000
X:110694160:TA:T	donor_loss	1.0000
X:110694161:A:C	donor_loss	1.0000
X:110694327:TGTCT:T	acceptor_gain	1.0000
X:110694328:GTCT:G	acceptor_gain	1.0000
X:110694329:TCT:T	acceptor_gain	1.0000
X:110694329:TCTC:T	acceptor_loss	1.0000

AlphaMissense

3017 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:110688689:C:G	C297S	1.000
X:110688690:A:T	C297S	1.000
X:110688716:C:G	C288S	1.000
X:110688717:A:G	C288R	1.000
X:110688717:A:T	C288S	1.000
X:110688760:C:A	W273C	1.000
X:110688760:C:G	W273C	1.000
X:110688762:A:G	W273R	1.000
X:110688762:A:T	W273R	1.000
X:110688800:C:G	C260S	1.000
X:110688801:A:G	C260R	1.000
X:110688801:A:T	C260S	1.000
X:110762752:C:A	W50C	1.000
X:110762752:C:G	W50C	1.000
X:110762754:A:G	W50R	1.000
X:110762754:A:T	W50R	1.000
X:110681495:C:A	W379C	0.999
X:110681495:C:G	W379C	0.999
X:110681497:A:G	W379R	0.999
X:110681497:A:T	W379R	0.999
X:110688623:C:G	C319S	0.999
X:110688624:A:T	C319S	0.999
X:110688626:C:G	C318S	0.999
X:110688627:A:G	C318R	0.999
X:110688627:A:T	C318S	0.999
X:110688674:C:G	C302S	0.999
X:110688675:A:G	C302R	0.999
X:110688675:A:T	C302S	0.999
X:110688690:A:G	C297R	0.999
X:110688709:A:C	C290W	0.999

dbSNP variants (sampled 300 via entrez): RS1000008664 (X:110705400 C>G), RS1000020833 (X:110718221 A>G), RS1000042119 (X:110721073 C>T), RS1000066144 (X:110773751 G>C), RS1000085891 (X:110763953 T>C), RS1000098644 (X:110691111 G>T), RS1000112640 (X:110723846 G>A), RS1000142966 (X:110714356 T>C), RS1000146461 (X:110774182 T>C), RS1000186472 (X:110755917 G>A,T), RS1000200322 (X:110765121 C>A), RS1000214025 (X:110772641 A>C), RS1000228149 (X:110705992 T>G), RS1000289400 (X:110763525 TAATC>T), RS1000324346 (X:110688938 C>T)

Disease associations

OMIM: gene MIM:300350 | disease phenotypes: MIM:249300, MIM:309300

GenCC curated gene-disease

Disease	Classification	Inheritance
isolated congenital megalocornea	Definitive	X-linked

Mondo (3): megalocornea (MONDO:0009576), isolated congenital megalocornea (MONDO:0010649), corneal disorder (MONDO:0000942)

Orphanet (1): Isolated congenital megalocornea (Orphanet:91489)

HPO phenotypes

16 total (17 of 16 shown, HPO-id order):

HPO	Term
HP:0000483	Astigmatism
HP:0000485	Megalocornea
HP:0000501	Glaucoma
HP:0000518	Cataract
HP:0000541	Retinal detachment
HP:0000616	Miosis
HP:0001084	Corneal arcus
HP:0001132	Lens subluxation
HP:0001419	X-linked recessive inheritance
HP:0007663	Reduced visual acuity
HP:0007765	Deep anterior chamber
HP:0007836	Mosaic corneal dystrophy
HP:0012632	Abnormal intraocular pressure
HP:0012805	Iris transillumination defect
HP:0100689	Decreased corneal thickness
HP:0100693	Iridodonesis
HP:0007660

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90011766_6	Glaucoma (primary open-angle)	4.000000e-07
GCST90014033_52	Haemorrhoidal disease	7.000000e-10

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003316	Corneal Diseases	C11.204
C562829	Megalocornea (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	4
trichostatin A	decreases expression, affects cotreatment	2
sodium arsenite	affects methylation, decreases expression, increases abundance	2
mercuric bromide	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Cadmium	decreases expression, increases abundance, increases expression	2
Dexamethasone	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression, affects cotreatment	1
methylmercuric chloride	decreases expression	1
uranyl acetate	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
arsenite	affects binding, decreases reaction	1
potassium chromate(VI)	increases expression	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
3-nitrobenzanthrone	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	increases expression	1
Ethanol	affects cotreatment, decreases expression	1
Arsenic	decreases expression, increases abundance	1

Clinical trials (associated diseases)

67 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05045053	PHASE4	UNKNOWN	Efficacy of Xiidra in Dry Eye Disease After Collagen Cross Linking
NCT06294015	PHASE4	UNKNOWN	Efficacy of 20% Autologous Serum Drops in the Treatment of Corneal Epitheliopathy Associated With Antihypertensive Glaucoma Drops.
NCT06636708	PHASE4	COMPLETED	Efficacy of Nanodropper-mediated Topical Anesthetic
NCT00447187	PHASE3	TERMINATED	Study to Assess the Efficacy and Safety of LX201 for Prevention of Corneal Allograft Rejection Episodes and Graft Failure in Subjects at Increased Immunological Risk
NCT03436576	PHASE3	UNKNOWN	Efficacy of Two Concentrations of Autologous Serum for the Treatment of Severe Dry Eye
NCT06601101	PHASE3	RECRUITING	Effects of Topical Insulin on Corneal Epithelium Healing After Corneal Crosslinking in Patients With Keratoconus
NCT03029104	PHASE2	TERMINATED	Collagen Cross-Linking With Ultraviolet-A in Asymmetric Corneas
NCT02374723	PHASE1	WITHDRAWN	Evaluation of Biosynthetic Constructs to Replace Donor Corneas
NCT05052554	PHASE1	WITHDRAWN	Study With QR-504a to Evaluate Safety, Tolerability & Corneal Endothelium Molecular Biomarker(s) in Subjects With FECD3
NCT05700864	PHASE1	WITHDRAWN	NGF Treatment for Patients With Neuropathic Corneal Pain
NCT07132437	PHASE1	COMPLETED	Phase I Clinical Study of ZKY001 Eye Drops in the Treatment of Corneal Epithelial Defect
NCT02148016	PHASE1/PHASE2	UNKNOWN	Corneal Epithelium Repair and Therapy Using Autologous Limbal Stem Cell Transplantation
NCT04484402	PHASE1/PHASE2	COMPLETED	Treatment of Patients With Inflammatory-dystrophic Diseases of the Cornea Using Autologous Stem Cells
NCT05280275	PHASE1/PHASE2	UNKNOWN	A Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin in Combination With Daratumumab, Lenalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Transplant Ineligible
NCT05573802	PHASE1/PHASE2	RECRUITING	A Study to Investigate Safety and Clinical Activity of Belantamab Mafodotin in Combination With Lenalidomide, Dexamethasone and Nirogacestat in Patients With Transplant Ineligible Newly Diagnosed Multiple Myeloma
NCT05581875	PHASE1/PHASE2	NOT_YET_RECRUITING	A Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin in Combination With Daratumumab, Pomalidomide and Dexamethasone in Patients With Relapsed/ Refractory Multiple Myeloma Previously Treated With One Line Therapy Who Are Lenalidomide Refractory
NCT01141985	EARLY_PHASE1	COMPLETED	New Disposable Contact Lens Patient Interface For The Lensx Laser
NCT06451172	EARLY_PHASE1	RECRUITING	Novel Antisense Oligonucleotide Eye Drops for Treating Antibiotic-Resistant Bacterial Keratitis
NCT00001310	Not specified	TERMINATED	Tissue Studies of Human Eye Diseases
NCT00006411	Not specified	COMPLETED	Cornea Donor Study
NCT00008541	Not specified	COMPLETED	Evaluation and Treatment of Patients With Corneal and External Diseases
NCT00029185	Not specified	COMPLETED	Study of Dehydrex in Patients With Corneal Erosion
NCT00050466	Not specified	COMPLETED	Dynamic Light Scattering and Keratoscopy for Corneal Examination
NCT00343473	Not specified	COMPLETED	Novel Diagnostics With Optical Coherence Tomography: Imaging the Anterior Eye
NCT00357435	Not specified	COMPLETED	Studies in Families With Corneal Dystrophy or Other Inherited Corneal Diseases
NCT00396188	Not specified	COMPLETED	Screening Aid to Identify Corneas That May Have Pathologies or Other Conditions
NCT00491439	Not specified	COMPLETED	Using in Vivo Confocal Microscope to Evaluate the Corneal Wound Healing After Various Ocular Surgeries
NCT00654888	Not specified	COMPLETED	Automated Lamellar Keratectomy in Symptomatic Patients With Bullous Keratopathy
NCT00804505	Not specified	COMPLETED	Hybrid SA RGP Center/S-H Skirt Daily Wear 90 Day Multicenter Study
NCT00810472	Not specified	COMPLETED	Functional Antigen Matching in Corneal Transplantation
NCT01384487	Not specified	COMPLETED	Nidek RS3000 Comparative Study
NCT02050880	Not specified	COMPLETED	OCT Agreement and Crossed Precision Study
NCT02291731	Not specified	COMPLETED	Autologous Serum Eye Drops With Contact Lenses for Corneal Epithelial Defects
NCT02344732	Not specified	COMPLETED	Effect of Systemic Oxygen on Corneal Epithelial Wound Healing in Diabetic Patients Undergoing Pars Plana Vitrectomy
NCT02348242	Not specified	COMPLETED	Ocular Surface Disorders in Patients in Intensive Care Units, a Comparative Study of Three Preventive Approaches
NCT02386774	Not specified	COMPLETED	Innovative Imaging of the Conjunctiva, Cornea, and Ocular Adnexa
NCT03421548	Not specified	WITHDRAWN	Implantable Intraocular Pressure Sensor for Glaucoma Monitoring in Patients With Boston Keratoprosthesis Type 1
NCT03619434	Not specified	UNKNOWN	Femtolaser Assisted Keratoplasty Versus Conventional Keratoplasty
NCT03706443	Not specified	COMPLETED	Tear Lipid Layer Thickness Changes With Use of Emollient and Non-Emollient Eye Drops
NCT03990506	Not specified	COMPLETED	Photorefractive Intrastromal Crosslinking (PiXL) for the Treatment of Progressive Keratoconus