COL18A1

Summary

COL18A1 (collagen type XVIII alpha 1 chain, HGNC:2195) is a protein-coding gene on chromosome 21q22.3, encoding Collagen alpha-1(XVIII) chain (P39060). Probably plays a major role in determining the retinal structure as well as in the closure of the neural tube.

This gene encodes the alpha chain of type XVIII collagen. This collagen is one of the multiplexins, extracellular matrix proteins that contain multiple triple-helix domains (collagenous domains) interrupted by non-collagenous domains. A long isoform of the protein has an N-terminal domain that is homologous to the extracellular part of frizzled receptors. Proteolytic processing at several endogenous cleavage sites in the C-terminal domain results in production of endostatin, a potent antiangiogenic protein that is able to inhibit angiogenesis and tumor growth. Mutations in this gene are associated with Knobloch syndrome. The main features of this syndrome involve retinal abnormalities, so type XVIII collagen may play an important role in retinal structure and in neural tube closure. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 80781 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Knobloch syndrome 1 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 16
• Clinical variants (ClinVar): 3,099 total — 137 pathogenic, 62 likely-pathogenic
• Phenotypes (HPO): 75
• Druggable target: yes
• MANE Select transcript: NM_001379500

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2195
Approved symbol	COL18A1
Name	collagen type XVIII alpha 1 chain
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	KS, KNO1
Ensembl gene	ENSG00000182871
Ensembl biotype	protein_coding
OMIM	120328
Entrez	80781

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 29 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000342220, ENST00000355480, ENST00000359759, ENST00000423214, ENST00000459895, ENST00000473212, ENST00000651438, ENST00000859059, ENST00000859060, ENST00000859061, ENST00000859062, ENST00000859063, ENST00000859064, ENST00000859065, ENST00000859066, ENST00000859067, ENST00000859068, ENST00000859069, ENST00000930594, ENST00000930595, ENST00000930596, ENST00000930597, ENST00000930598, ENST00000930599, ENST00000930600, ENST00000930601, ENST00000930602, ENST00000970097, ENST00000970098, ENST00000970099, ENST00000970100

RefSeq mRNA: 3 — MANE Select: NM_001379500 NM_001379500, NM_030582, NM_130444

CCDS: CCDS42971, CCDS42972, CCDS77643

Canonical transcript exons

ENST00000651438 — 42 exons

Exon	Start	End
ENSE00001542501	45512188	45513720
ENSE00001595082	45478327	45478353
ENSE00001601591	45504416	45504556
ENSE00001603969	45405379	45405473
ENSE00001617212	45480467	45480520
ENSE00001619008	45480700	45480858
ENSE00001627003	45477411	45477487
ENSE00001638049	45477750	45477965
ENSE00001638654	45504011	45504054
ENSE00001640622	45473895	45473981
ENSE00001649344	45492535	45492564
ENSE00001654135	45468242	45468786
ENSE00001654943	45493163	45493225
ENSE00001665017	45481963	45482025
ENSE00001677445	45489486	45489521
ENSE00001685925	45479902	45479964
ENSE00001701626	45492687	45492713
ENSE00001705636	45487447	45487509
ENSE00001712155	45488418	45488444
ENSE00001717154	45505838	45505966
ENSE00001717282	45497599	45497661
ENSE00001722709	45475476	45475535
ENSE00001725836	45505358	45505431
ENSE00001740104	45476351	45476480
ENSE00001742681	45491225	45491314
ENSE00001748652	45482795	45482821
ENSE00001758572	45480070	45480156
ENSE00001759875	45490275	45490346
ENSE00001760845	45486861	45486992
ENSE00001761211	45505134	45505278
ENSE00001792883	45490836	45490871
ENSE00002238826	45507561	45507593
ENSE00003523340	45493501	45493575
ENSE00003563378	45494862	45494915
ENSE00003582147	45496500	45496568
ENSE00003582883	45509356	45509601
ENSE00003588504	45511111	45511226
ENSE00003594559	45494545	45494571
ENSE00003601528	45495358	45495432
ENSE00003624748	45497050	45497092
ENSE00003643178	45510064	45510261
ENSE00003847686	45405165	45405241

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 99.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.4264 / max 1630.6824, expressed in 1479 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189546	51.9617	1468
189549	8.9132	567
189548	0.5261	221
209343	0.0254	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right coronary artery	UBERON:0001625	99.37	gold quality
popliteal artery	UBERON:0002250	99.32	gold quality
tibial artery	UBERON:0007610	99.32	gold quality
descending thoracic aorta	UBERON:0002345	99.23	gold quality
right lobe of liver	UBERON:0001114	99.21	gold quality
aorta	UBERON:0000947	99.20	gold quality
thoracic aorta	UBERON:0001515	99.09	gold quality
ascending aorta	UBERON:0001496	99.07	gold quality
endocervix	UBERON:0000458	99.05	gold quality
metanephros cortex	UBERON:0010533	99.05	gold quality
left ovary	UBERON:0002119	98.97	gold quality
right ovary	UBERON:0002118	98.96	gold quality
left coronary artery	UBERON:0001626	98.95	gold quality
coronary artery	UBERON:0001621	98.89	gold quality
right uterine tube	UBERON:0001302	98.88	gold quality
ectocervix	UBERON:0012249	98.10	gold quality
left uterine tube	UBERON:0001303	97.95	gold quality
liver	UBERON:0002107	97.64	gold quality
body of uterus	UBERON:0009853	97.64	gold quality
sural nerve	UBERON:0015488	97.64	gold quality
tibial nerve	UBERON:0001323	97.47	gold quality
adenohypophysis	UBERON:0002196	97.44	gold quality
omental fat pad	UBERON:0010414	97.00	gold quality
peritoneum	UBERON:0002358	96.99	gold quality
right lobe of thyroid gland	UBERON:0001119	96.97	gold quality
left lobe of thyroid gland	UBERON:0001120	96.97	gold quality
blood vessel layer	UBERON:0004797	96.95	gold quality
renal medulla	UBERON:0000362	96.88	gold quality
right atrium auricular region	UBERON:0006631	96.84	gold quality
pituitary gland	UBERON:0000007	96.78	gold quality

Single-cell (SCXA)

Detected in 22 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	1135.72
E-HCAD-11	yes	1023.34
E-MTAB-8142	yes	944.15
E-GEOD-137537	yes	580.07
E-ENAD-20	yes	138.20
E-HCAD-31	yes	27.34
E-MTAB-5061	yes	27.12
E-MTAB-8410	yes	26.38
E-GEOD-135922	yes	25.35
E-GEOD-81547	yes	22.55
E-HCAD-10	yes	17.96
E-MTAB-6678	yes	13.49
E-CURD-46	yes	10.58
E-GEOD-134144	yes	8.54
E-ANND-3	yes	8.06

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXA2, NFIC, SP1, TP53

Literature-anchored findings (GeneRIF, showing 40)

• Hypoxia down-regulates endostatin production by microvascular endothelial cells and pericytes (PMID:11700031)
• An increase of about one-third of normal endostatin serum levels may represent an effective therapeutic dose to significantly inhibit many solid tumours. (PMID:11781696)
• Endostatin causes G1 arrest of endothelial cells through inhibition of cyclin D1. (PMID:11815623)
• Endostatin plays a crucial role in endothelial tubule stabilization, maintenance and integrity during angiogenesis. (PMID:11911017)
• type XV and XVIII collagens are expressed in specialized basement membranes. (PMID:11937714)
• production in head and neck carcinoma modulated by hsp47 (PMID:12174873)
• Serum levels of angiogenin, basic fibroblast growth factor and endostatin in patients receiving intensive chemotherapy for acute myelogenous leukemia. (PMID:12209593)
• There is a positive correlation between the levels of tissue endostatin and malignancy grades in gliomas. The endostatin may be released near the tumor blood vessels with hyperplasia to counteract angiogenic stimuli in malignant gliomas. (PMID:12231538)
• Data are consistent with a model of endostatin with two binding sites: one mainly to laminin in the basement membrane and the other to heparan sulfates on the cell surface. (PMID:12237301)
• Collagen XVIII is a heparan sulfate proteoglycan associated with vascular amyloid beta and senile plaques in Alzheimer Disease. (PMID:12408231)
• Molecular analysis of collagen XVIII reveals novel mutations, presence of a third isoform, and possible genetic heterogeneity in Knobloch syndrome (PMID:12415512)
• Accumulation of endostatin/collagenXVIII in brains of patients who died with cerebral malaria. (PMID:12458056)
• Aberrant neuronal and paracellular deposition of endostatin in brains of patients with Alzheimer’s disease. (PMID:12486154)
• endostatin competes with fibronectin/RGD cyclic peptide to bind alpha 5 beta 1 integrin (PMID:12682293)
• A recombinant fusion version of this protein may be a therapeutic agent for breast cancer. (PMID:12839947)
• level of endostatin was lower in the group of chronic lymphocytic leukemia patients with progressive disease as compared to patients with stable disease (PMID:12857600)
• Data indicate that serum endostatin levels are higher in multiple myeloma patients than in healthy controls, with the highest values found during the active phase of the disease. (PMID:14514474)
• analyses of age-matched study groups revealed elevated medians of endostatin concentration for severely and mildly preeclamptic patients (PMID:14519482)
• Analysis of knobloch syndrome-associated mutations in COL18A1 and genetic variation in endostatin. (PMID:14695535)
• Plasma endostatin increased after surgical removal of primary tumor. Decreased intratumoral microvessels in patients with higher endostatin levels may be due to apoptosis-inducing effect of endostatin on microvascular endothelial cells. (PMID:14732364)
• Pleural mesothelial cells play a key role in the antiangiogenesis process by producing endostatin in the pleural space (PMID:14760864)
• there is a putative integrin-binding sequence with anti-migratory activity within endostatin (PMID:14973128)
• Lentivirus-mediated gene transfer might represent an effective strategy for expression of angioinhibitory peptides to achieve inhibition of human bladder cancer proliferation and tumor progression. (PMID:15014038)
• E-selectin is required for the antiangiogenic activity of endostatin in vivo and ex vivo and confers endostatin sensitivity to nonresponsive human endothelial cells in vitro (PMID:15148373)
• Collagen XVIII and enamelysin were co-localized in the developing enamel matrix and stratum intermedium and in the enamel-like tumor matrix of odontogenic tumors. (PMID:15296943)
• Expression of collagen XVIII in tumor tissue is strongly associated with a poorer outcome in non-small-cell lung cancer and correlates with elevated levels of circulating serum endostatin. (PMID:15328173)
• Naked endostatin plasmid intratumoral injection can get a similar gene transfection efficiency to liposome-DNA complex when used in situ in inhibiting cell growth. (PMID:15334690)
• Hypoxia downregulates the concentration of endostatin in the culture media of human endometrial stromal cells. (PMID:15374730)
• Spatial and temporal expression of endostatin/collagen XVIII in cartilaginous tissue and its inactivation of VEGF signalling suggests that it is important for development and maintenance of avascular zones in cartilage and fibrocartilage. (PMID:15464359)
• Endostatin diminishes the levels of nitric oxide (NO) whereas NO donors enhanced VEGF expression and collagen XVIII expression. (PMID:15540202)
• Increased endostatin/collagen XVIII expression correlated with hepatoma progression and predicted poor prognosis for patients with hepatocellular carcinoma. (PMID:15605080)
• angiostatic function is heparan sulfate-dependent, and in situ-binding of endostatin to endothelial cells is increased by heparan sulfates (PMID:15694132)
• Biologically active endostatin, generated by matrix metalloproteases from collagen XVIII, may participate in the inhibition of endothelial cell proliferation, migration and angiogenesis. (PMID:15950618)
• results demonstrate that there is a direct connection between dependence of endostatin activity on heparin-like glycosaminoglycans and its ability to antagonize bFGF (PMID:15985216)
• Overexpression of endostatin effectively inhibits the growth of ovarian cancer. (PMID:16008891)
• Elevated serum levels of endostatin were observed in patients with idiopathic pulmonary fibrosis (PMID:16025479)
• Mechanically induced VEGF is involved in the destruction and endostatin in the maintenance of avascular tissues of the bone and joint system. (review) (PMID:16320826)
• Significantly higher serum concentrations of endostatin are associated with lung carcinoma (PMID:16358965)
• data show that inhibition of PI3K/protein kinase B (PKB) increased endostatin-induced apoptosis, and that endostatin-induced cell death is physiologically linked to PKB-mediated cell survival through caspase-8 (PMID:16466644)
• The results indicate that the antiangiogenic functions of endostatin(ES) critically depend on the mode of delivery and the site of expression. (PMID:16793908)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	col18a1a	ENSDARG00000036558
danio_rerio	col18a1b	ENSDARG00000095901
mus_musculus	Col18a1	ENSMUSG00000001435
rattus_norvegicus	Col18a1	ENSRNOG00000001229

Paralogs (37): COL9A2 (ENSG00000049089), COL23A1 (ENSG00000050767), COL11A1 (ENSG00000060718), COL17A1 (ENSG00000065618), COL5A3 (ENSG00000080573), COL4A4 (ENSG00000081052), COL16A1 (ENSG00000084636), COL9A3 (ENSG00000092758), COL20A1 (ENSG00000101203), COL1A1 (ENSG00000108821), COL9A1 (ENSG00000112280), COL7A1 (ENSG00000114270), COL21A1 (ENSG00000124749), COL5A1 (ENSG00000130635), COL4A2 (ENSG00000134871), COL2A1 (ENSG00000139219), COL6A1 (ENSG00000142156), COL6A2 (ENSG00000142173), EDA (ENSG00000158813), COL26A1 (ENSG00000160963), COL1A2 (ENSG00000164692), COL3A1 (ENSG00000168542), COL4A3 (ENSG00000169031), COL22A1 (ENSG00000169436), COL24A1 (ENSG00000171502), EMID1 (ENSG00000186998), COL4A1 (ENSG00000187498), COL4A5 (ENSG00000188153), COL25A1 (ENSG00000188517), COL27A1 (ENSG00000196739), COL13A1 (ENSG00000197467), COL4A6 (ENSG00000197565), COL11A2 (ENSG00000204248), COL5A2 (ENSG00000204262), COL15A1 (ENSG00000204291), COLQ (ENSG00000206561), COL28A1 (ENSG00000215018)

Protein

Protein identifiers

Collagen alpha-1(XVIII) chain — P39060 (reviewed: P39060)

All UniProt accessions (3): P39060, H7BXV5, H7C457

UniProt curated annotations — full annotation on UniProt →

Function. Probably plays a major role in determining the retinal structure as well as in the closure of the neural tube. May regulate extracellular matrix-dependent motility and morphogenesis of endothelial and non-endothelial cells; the function requires homotrimerization and implicates MAPK signaling. Potently inhibits endothelial cell proliferation and angiogenesis. May inhibit angiogenesis by binding to the heparan sulfate proteoglycans involved in growth factor signaling. Inhibits VEGFA-induced endothelial cell proliferation and migration. Seems to inhibit VEGFA-mediated signaling by blocking the interaction of VEGFA to its receptor KDR/VEGFR2. Modulates endothelial cell migration in an integrin-dependent manner implicating integrin ITGA5:ITGB1 and to a lesser extent ITGAV:ITGB3 and ITGAV:ITGB5. May negatively regulate the activity of homotrimeric non-collagenous domain 1.

Subunit / interactions. Forms homotrimers. Recombinant non-collagenous domain 1 has stronger affinity to NID1, HSPG2 and laminin-1:NID1 complex and lower affinity to FBLN1 and FBLN2 than endostatin. Monomeric. Interacts with KDR/VEGFR2. Interacts with the ITGA5:ITGB1 complex. Interacts with NID1, HSPG2, laminin-1:NID1 complex, FBLN1 and FBLN2.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Basement membrane Secreted. Basement membrane. Secreted Secreted.

Tissue specificity. Detected in placenta (at protein level). Present in multiple organs with highest levels in liver, lung and kidney.

Post-translational modifications. Prolines at the third position of the tripeptide repeating unit (G-X-Y) of the triple-helical regions are hydroxylated. Circulating endostatins are found as sialoglycoprotein and asialoglycoprotein structures. Undergoes proteolytic processing by CTSL/cathepsin-L and elastase-like proteases to generate both non-collagenous domain 1 trimers and endostatin monomers. In tissue extracts (brain, skeletal muscle, heart, kidney, testis and liver) predominantly bands of approximately 38 kDa are detected; recombinant non-collagenous domain 1 shows similar mobility. In vitro, several proteolytic cleavage sites in the non-collagenous domain 1 hinge region generating different endostatin-like peptides are reported.

Disease relevance. Knobloch syndrome 1 (KNO1) [MIM:267750] A developmental disorder primarily characterized by typical eye abnormalities, including high myopia, cataracts, dislocated lens, vitreoretinal degeneration, and retinal detachment, with occipital skull defects, which can range from occipital encephalocele to occult cutis aplasia. The disease is caused by variants affecting the gene represented in this entry. Glaucoma, primary closed-angle (GLCC) [MIM:618880] An autosomal dominant form of primary glaucoma, an ocular disease characterized by a marked increase of intraocular pressure causing damage to eye structures and function. GLCC is characterized by elevated intraocular pressure due to iridocorneal angle closure with retention of the aqueous humor in the anterior chamber. Iridocorneal angle changes are apparent in the fourth to fifth decade of life, and patients manifest age-related variation in the severity of glaucomatous damage. The disease may be caused by variants affecting the gene represented in this entry.

Polymorphism. There is an association between a polymorphism in position 1675 and prostate cancer. Heterozygous Asn-1675 individuals have a 2.5 times increased chance of developing prostate cancer as compared with homozygous Asp-1675 individuals.

Miscellaneous. Produced by alternative promoter usage. Produced by alternative splicing of isoform 1. Produced by alternative promoter usage.

Similarity. Belongs to the multiplexin collagen family.

Isoforms (3)

UniProt ID	Names	Canonical?
P39060-3	1, NC1-728	yes
P39060-1	2, Long, NC-493
P39060-2	3, Short, NC1-303

RefSeq proteins (3): NP_001366429, NP_085059, NP_569711 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008160	Collagen	Repeat
IPR010363	DUF959_COL18_N	Domain
IPR010515	Collagenase_NC10/endostatin	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR020067	Frizzled_dom	Domain
IPR035523	Collagen_XVIII_Fz	Domain
IPR036790	Frizzled_dom_sf	Homologous_superfamily
IPR045463	XV/XVIII_trimerization_dom	Domain
IPR048287	TSPN-like_N	Domain
IPR050149	Collagen_superfamily	Family

Pfam: PF01391, PF01392, PF06121, PF06482, PF20010

UniProt features (132 total): region of interest 27, compositionally biased region 26, sequence conflict 19, strand 13, helix 9, sequence variant 9, disulfide bond 7, glycosylation site 6, binding site 4, chain 3, splice variant 3, domain 2, signal peptide 1, turn 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
9BNC	X-RAY DIFFRACTION	1.4
9BNB	X-RAY DIFFRACTION	1.5
3HSH	X-RAY DIFFRACTION	1.8
1BNL	X-RAY DIFFRACTION	2.9
3HON	X-RAY DIFFRACTION	3
9BND	ELECTRON MICROSCOPY	3.19
9BNF	ELECTRON MICROSCOPY	3.33
9BNE	ELECTRON MICROSCOPY	3.43
9BNG	ELECTRON MICROSCOPY	3.73

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P39060-F1	51.77	0.16

Functional residue map

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

Ligand- & substrate-binding residues (4): 1572; 1574; 1582; 1647

Post-translational modifications (1): 696

Disulfide bonds (7): 334–397, 344–390, 381–419, 408–443, 412–432, 1604–1744, 1706–1736

Glycosylation sites (6): 68, 129, 164, 889, 926, 1567

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1442490	Collagen degradation
R-HSA-1592389	Activation of Matrix Metalloproteinases
R-HSA-1650814	Collagen biosynthesis and modifying enzymes
R-HSA-2022090	Assembly of collagen fibrils and other multimeric structures
R-HSA-216083	Integrin cell surface interactions
R-HSA-3000157	Laminin interactions
R-HSA-8948216	Collagen chain trimerization

MSigDB gene sets: 421 (showing top): GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, AGGAAGC_MIR5163P, GOBP_EPITHELIUM_DEVELOPMENT, WANG_CLIM2_TARGETS_UP, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOCC_COLLAGEN_TRIMER, PEREZ_TP63_TARGETS, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, HUMMERICH_MALIGNANT_SKIN_TUMOR_UP, KANNAN_TP53_TARGETS_DN, LIEN_BREAST_CARCINOMA_METAPLASTIC

GO Biological Process (11): skeletal system development (GO:0001501), angiogenesis (GO:0001525), endothelial cell morphogenesis (GO:0001886), cell adhesion (GO:0007155), visual perception (GO:0007601), negative regulation of cell population proliferation (GO:0008285), response to xenobiotic stimulus (GO:0009410), animal organ morphogenesis (GO:0009887), response to hydrostatic pressure (GO:0051599), anatomical structure morphogenesis (GO:0009653), regulation of cell population proliferation (GO:0042127)

GO Molecular Function (3): extracellular matrix structural constituent conferring tensile strength (GO:0030020), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), collagen trimer (GO:0005581), basement membrane (GO:0005604), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Degradation of the extracellular matrix	2
Collagen formation	2
Extracellular matrix organization	2
Collagen biosynthesis and modifying enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell population proliferation	2
system development	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
endothelial cell development	1
epithelial cell morphogenesis	1
cellular process	1
sensory perception of light stimulus	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
response to chemical	1
anatomical structure morphogenesis	1
animal organ development	1
response to stress	1
response to water	1
developmental process	1
anatomical structure development	1
regulation of cellular process	1
extracellular matrix structural constituent	1
cation binding	1
binding	1
cellular anatomical structure	1
protein-containing complex	1
extracellular matrix	1
endoplasmic reticulum	1
intracellular organelle lumen	1
external encapsulating structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

2112 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COL18A1	GPC1	P35052	965
COL18A1	DR1	Q01658	959
COL18A1	KDR	P35968	945
COL18A1	NUCLEOLIN	P19338	914
COL18A1	PLG	P00747	889
COL18A1	HSPG2	P98160	865
COL18A1	GPC4	O75487	840
COL18A1	THBS1	P07996	824
COL18A1	FN1	P02751	815
COL18A1	CERT1	Q9Y5P4	797
COL18A1	ADAMTS8	Q9UP79	789
COL18A1	FLT4	P35916	772
COL18A1	VTN	P01141	745
COL18A1	FLT1	P16057	739
COL18A1	FGF7	P21781	693

IntAct

85 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
P4HA2	P4HB	psi-mi:“MI:0914”(association)	0.740
MMP9	TIMP1	psi-mi:“MI:0914”(association)	0.640
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
MMP2	COL4A1	psi-mi:“MI:0914”(association)	0.640
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
C1QTNF9B	PLOD3	psi-mi:“MI:0914”(association)	0.530
ADIPOQ	C1QL1	psi-mi:“MI:0914”(association)	0.530
PLOD3	COL4A1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
PLOD3	PLOD2	psi-mi:“MI:0914”(association)	0.530
OS9	AGRN	psi-mi:“MI:0914”(association)	0.530
LAIR2	LAMA5	psi-mi:“MI:0914”(association)	0.530
COL18A1	COL18A1	psi-mi:“MI:0407”(direct interaction)	0.440
APP	COL18A1	psi-mi:“MI:0407”(direct interaction)	0.440
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
L1TD1	MYO1C	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
	CCN1	psi-mi:“MI:0914”(association)	0.350
TECPR1	PLOD3	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (119): COL18A1 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS)

ESM2 similar proteins: A0A060WQA3, A0MSJ1, A5PN28, A6NHN0, A8WGB1, C7DZK3, O35206, O60279, O88207, O89103, P07897, P13608, P13942, P16112, P20908, P20909, P25940, P39059, P39060, P39061, P55068, P83371, Q07092, Q14767, Q17RW2, Q28019, Q28062, Q28343, Q28670, Q29011, Q30D77, Q32S24, Q3MI99, Q4ZJM7, Q5QNQ9, Q60467, Q61245, Q61282, Q64739, Q6UXH8

Diamond homologs: O35206, P39059, P39060, P39061, P97401, Q5RF67, Q92765, Q95117, Q9IA95, Q80YN4, Q9Y5Q5, Q9Z319, A0A0K3AWM6, B3DIG4, G5ECQ2, O00144, O42579, O57328, O57329, O60353, O70421, O75084, O77438, O93274, P18537, P58421, Q08463, Q08464, Q13467, Q14332, Q24760, Q498S8, Q5BL72, Q5RCN4, Q61086, Q61088, Q61089, Q61090, Q61091, Q6FHJ7

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
COL18A1	up-regulates	ECM_synthesis
COL18A1	up-regulates	“A5/b1 integrin”	binding
COL18A1	down-regulates	Angiogenesis

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 93 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Collagen biosynthesis and modifying enzymes	10	25.8×	2e-09
Collagen degradation	5	13.3×	4e-03
Extra-nuclear estrogen signaling	5	12.9×	4e-03
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	7	9.2×	2e-03
Post-translational protein phosphorylation	6	9.1×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
collagen fibril organization	7	18.9×	3e-05
extracellular matrix organization	7	10.3×	1e-03
positive regulation of cell migration	8	6.0×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

3099 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	137
Likely pathogenic	62
Uncertain significance	1176
Likely benign	1257
Benign	253

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1013194	NM_001379500.1(COL18A1):c.2917C>T (p.Gln973Ter)	Pathogenic
1322108	NM_001379500.1(COL18A1):c.1924-2_1924del	Pathogenic
1354320	NM_001379500.1(COL18A1):c.1488del (p.Gly497fs)	Pathogenic
1356160	NM_001379500.1(COL18A1):c.2102dup (p.Leu702fs)	Pathogenic
1362146	NM_001379500.1(COL18A1):c.394del (p.His132fs)	Pathogenic
1364335	NC_000021.9:g.45490838del	Pathogenic
1366287	NM_001379500.1(COL18A1):c.1187_1200dup (p.Pro401fs)	Pathogenic
1366539	NM_001379500.1(COL18A1):c.367del (p.Gly122_Val123insTer)	Pathogenic
1367951	NM_001379500.1(COL18A1):c.2969_2978dup (p.Gly994fs)	Pathogenic
1381645	NM_001379500.1(COL18A1):c.1459C>T (p.Arg487Ter)	Pathogenic
1387227	NM_001379500.1(COL18A1):c.1790dup (p.Gly598fs)	Pathogenic
1395721	NM_001379500.1(COL18A1):c.2558dup (p.Pro854fs)	Pathogenic
1406673	NM_001379500.1(COL18A1):c.3279del (p.Val1094fs)	Pathogenic
1411374	NM_001379500.1(COL18A1):c.481C>T (p.Gln161Ter)	Pathogenic
1416390	NM_001379500.1(COL18A1):c.2927_2978del (p.Pro976fs)	Pathogenic
1416901	NM_001379500.1(COL18A1):c.2118del (p.Gly707fs)	Pathogenic
1417839	NM_001379500.1(COL18A1):c.3044_3062del (p.Pro1015fs)	Pathogenic
1424228	NM_001379500.1(COL18A1):c.2786dup (p.Gly930fs)	Pathogenic
1426630	NM_001379500.1(COL18A1):c.2781dup (p.Gly928fs)	Pathogenic
1429000	NM_001379500.1(COL18A1):c.2111del (p.Gly704fs)	Pathogenic
1429645	NM_001379500.1(COL18A1):c.2707C>T (p.Gln903Ter)	Pathogenic
1430023	NM_001379500.1(COL18A1):c.2979_2988dup (p.Ser997fs)	Pathogenic
1430381	NM_001379500.1(COL18A1):c.2958_2985del (p.Pro987fs)	Pathogenic
1432778	NM_001379500.1(COL18A1):c.2669_2670insT (p.Gly892fs)	Pathogenic
1440746	NM_001379500.1(COL18A1):c.3306dup (p.Tyr1103fs)	Pathogenic
1442812	NM_001379500.1(COL18A1):c.1070del (p.Pro357fs)	Pathogenic
1444038	NM_001379500.1(COL18A1):c.2525del (p.Pro842fs)	Pathogenic
1451864	NM_001379500.1(COL18A1):c.3048dup (p.Pro1017fs)	Pathogenic
1452039	NM_001379500.1(COL18A1):c.2824_2840del (p.Gly942fs)	Pathogenic
1452623	NM_001379500.1(COL18A1):c.3053dup (p.Gly1019fs)	Pathogenic

SpliceAI

6648 predictions. Top by Δscore:

Variant	Effect	Δscore
21:45468238:GCA:G	acceptor_loss	1.0000
21:45468239:CAG:C	acceptor_gain	1.0000
21:45468240:A:AC	acceptor_loss	1.0000
21:45468240:A:AG	acceptor_gain	1.0000
21:45468240:AGA:A	acceptor_gain	1.0000
21:45468240:AGAGC:A	acceptor_gain	1.0000
21:45468241:G:A	acceptor_loss	1.0000
21:45468241:G:GC	acceptor_gain	1.0000
21:45468241:GA:G	acceptor_gain	1.0000
21:45468241:GAG:G	acceptor_gain	1.0000
21:45468241:GAGC:G	acceptor_gain	1.0000
21:45468241:GAGCG:G	acceptor_gain	1.0000
21:45473893:AGGG:A	acceptor_gain	1.0000
21:45473894:GGGG:G	acceptor_gain	1.0000
21:45476345:CTCCA:C	acceptor_loss	1.0000
21:45476346:TCCA:T	acceptor_loss	1.0000
21:45476347:CCAGG:C	acceptor_loss	1.0000
21:45476349:AG:A	acceptor_gain	1.0000
21:45476350:G:A	acceptor_loss	1.0000
21:45476350:GG:G	acceptor_gain	1.0000
21:45476350:GGGC:G	acceptor_gain	1.0000
21:45476477:GGAG:G	donor_gain	1.0000
21:45476478:G:GT	donor_gain	1.0000
21:45476478:GAG:G	donor_gain	1.0000
21:45476478:GAGG:G	donor_loss	1.0000
21:45476479:AGG:A	donor_loss	1.0000
21:45476480:GGTAA:G	donor_loss	1.0000
21:45476481:G:GG	donor_gain	1.0000
21:45477409:A:AG	acceptor_gain	1.0000
21:45477410:G:GG	acceptor_gain	1.0000

AlphaMissense

8469 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:45510133:T:A	C1604S	0.999
21:45510133:T:C	C1604R	0.999
21:45510134:G:C	C1604S	0.999
21:45510135:C:G	C1604W	0.999
21:45512363:T:C	C1744R	0.999
21:45512364:G:A	C1744Y	0.999
21:45512365:C:G	C1744W	0.999
21:45510124:G:C	D1601H	0.998
21:45510134:G:A	C1604Y	0.998
21:45510134:G:T	C1604F	0.998
21:45511134:G:C	W1654C	0.998
21:45511134:G:T	W1654C	0.998
21:45512204:T:A	W1691R	0.998
21:45512204:T:C	W1691R	0.998
21:45512206:G:C	W1691C	0.998
21:45512206:G:T	W1691C	0.998
21:45512363:T:A	C1744S	0.998
21:45512364:G:C	C1744S	0.998
21:45510071:T:C	L1583P	0.997
21:45510125:A:T	D1601V	0.997
21:45510255:C:A	N1644K	0.997
21:45510255:C:G	N1644K	0.997
21:45511132:T:A	W1654R	0.997
21:45511132:T:C	W1654R	0.997
21:45512364:G:T	C1744F	0.997
21:45512370:A:T	E1746V	0.997
21:45512374:C:A	N1747K	0.997
21:45512374:C:G	N1747K	0.997
21:45510077:C:A	A1585E	0.996
21:45510175:C:A	R1618S	0.996

dbSNP variants (sampled 300 via entrez): RS1000021366 (21:45469869 T>C), RS1000048687 (21:45479436 A>G), RS1000063134 (21:45495392 A>C), RS1000074584 (21:45443531 T>A,C,G), RS1000099247 (21:45496904 CCT>C), RS1000100726 (21:45499221 T>A,C), RS1000106408 (21:45493127 AGCC>A), RS1000124397 (21:45433729 A>G), RS1000130961 (21:45474397 G>A), RS1000147406 (21:45415338 A>G), RS1000177591 (21:45447031 G>A), RS1000179253 (21:45405005 G>A,C,T), RS1000179804 (21:45508647 G>A), RS1000183639 (21:45474127 G>A), RS1000192775 (21:45439244 C>T)

Disease associations

OMIM: gene MIM:120328 | disease phenotypes: MIM:267750, MIM:618880, MIM:116200, MIM:268000, MIM:602482, MIM:158350

GenCC curated gene-disease

Disease	Classification	Inheritance
Knobloch syndrome 1	Definitive	Autosomal recessive
Knobloch syndrome	Strong	Autosomal recessive
hereditary glaucoma, primary closed-angle	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Knobloch syndrome 1	Definitive	AR

Mondo (12): Knobloch syndrome (MONDO:0800166), hereditary glaucoma, primary closed-angle (MONDO:0030038), Knobloch syndrome 1 (MONDO:0800167), ocular motility disease (MONDO:0001584), pathologic nystagmus (MONDO:0004843), cataract (MONDO:0005129), inherited retinal dystrophy (MONDO:0019118), retinal disorder (MONDO:0005283), retinitis pigmentosa (MONDO:0019200), Axenfeld-Rieger syndrome type 3 (MONDO:0011233), Cowden syndrome 1 (MONDO:0008021), (MONDO:0009977)

Orphanet (4): Knobloch syndrome (Orphanet:1571), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791), Axenfeld-Rieger syndrome (Orphanet:782)

HPO phenotypes

75 total (30 of 75 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000075	Renal duplication
HP:0000076	Vesicoureteral reflux
HP:0000081	Duplicated collecting system
HP:0000126	Hydronephrosis
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000286	Epicanthus
HP:0000341	Narrow forehead
HP:0000414	Bulbous nose
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000506	Telecanthus
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000529	Progressive visual loss
HP:0000533	Chorioretinal atrophy
HP:0000541	Retinal detachment
HP:0000543	Optic disc pallor
HP:0000545	Myopia
HP:0000572	Visual loss
HP:0000585	Band keratopathy
HP:0000608	Macular degeneration
HP:0000639	Nystagmus
HP:0000640	Gaze-evoked nystagmus
HP:0000666	Horizontal nystagmus
HP:0000667	Phthisis bulbi

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001530_12	Hippocampal atrophy	8.000000e-07
GCST004138_1	Early-onset Parkinson’s disease	8.000000e-240
GCST004952_39	Ankle injury	4.000000e-08
GCST005024_90	Pursuit maintenance gain	2.000000e-06
GCST006143_14	Bone mineral density (total hip)	8.000000e-06
GCST006585_1716	Blood protein levels	6.000000e-10
GCST006613_1	Triglycerides	1.000000e-28
GCST006614_100	Total cholesterol levels	4.000000e-09
GCST007849_2	Triglycerides	2.000000e-11
GCST007849_4	Triglycerides	2.000000e-16
GCST010241_75	Apolipoprotein A1 levels	8.000000e-14
GCST010242_167	HDL cholesterol levels	1.000000e-11
GCST010573_3	Cardiorespiratory fitness (800m run time)	1.000000e-08
GCST010703_141	Brain morphology (MOSTest)	5.000000e-08
GCST90002401_341	Platelet distribution width	1.000000e-11
GCST90010427_27	Left–right brain asymmetry	8.000000e-10

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0005039	hippocampal atrophy
EFO:1002021	ankle injury
EFO:0008433	pursuit maintenance gain measurement
EFO:0007702	hip bone mineral density
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004328	exercise test
EFO:0004346	neuroimaging measurement
EFO:0007984	platelet component distribution width

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D002386	Cataract	C11.510.245
D009759	Nystagmus, Pathologic	C10.292.562.675; C11.590.400
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C537209	Knobloch syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2364188 (PROTEIN COMPLEX GROUP)

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

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7499	COL18A1, SLC19A1		0.00	0
rs2274808	COL18A1		0.00	0
rs7279445	COL18A1, SLC19A1		0.00	0
rs9977268	COL18A1, SLC19A1	3	0.00	1	methotrexate
rs11702425	COL18A1, SLC19A1		0.00	0
rs17004785	COL18A1, SLC19A1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases expression	4
Aflatoxin B1	affects expression, decreases expression, increases methylation	4
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases methylation	3
Valproic Acid	decreases expression, increases expression	3
Cyclosporine	decreases expression, decreases methylation	3
Resveratrol	decreases expression, affects cotreatment	2
Vehicle Emissions	decreases expression, decreases reaction, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Genistein	increases expression, decreases expression	2
Particulate Matter	decreases expression, decreases reaction, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	decreases expression, affects cotreatment	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
deoxynivalenol	decreases expression	1
titanium dioxide	increases expression, affects binding	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	decreases methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression, decreases reaction, increases chemical synthesis	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation, decreases methylation	1
aflatoxin B2	decreases methylation	1
triacsin C	decreases expression	1
nivalenol	decreases expression	1
di-n-butylphosphoric acid	affects expression	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D0QH	ZSZOCi001-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00273221	PHASE4	UNKNOWN	Combined Phacotube vs Phacotrabeculectomy:A Randomized Controlled Trial
NCT00312299	PHASE4	COMPLETED	Posterior Capsule Opacification Study
NCT00345046	PHASE4	COMPLETED	A Comparison of Three Different Formulations of Prednisolone Acetate 1%
NCT00347243	PHASE4	COMPLETED	Wavefront Analisys and Contrast Sensitivity of Spherical and Aspherical Intraocular Lenses
NCT00347503	PHASE4	COMPLETED	Aqueous Concentrations and PGE2 Inhibition of Ketorolac 0.4% vs. Bromfenac 0.09% in Cataract Patients
NCT00348244	PHASE4	COMPLETED	Ketorolac vs. Steroid in the Prevention of CME
NCT00348270	PHASE4	COMPLETED	Comparison of the Quality of Vision Provided by AMO Tecnis Z9000 and Alcon Laboratories MA60 Acrysof Posterior Chamber Intraocular Lenses
NCT00348582	PHASE4	COMPLETED	Acular LS vs. Nevanac in Post op Inflammation Following Cataract Surgery
NCT00348621	PHASE4	COMPLETED	A Study of Interventions to Reduce Disability From Visual Loss in Nursing Home Residents
NCT00349583	PHASE4	COMPLETED	Efficacy of Topical Cyclosporine Versus Tears for Improving Visual Outcomes Following Multifocal IOL Implantation
NCT00355446	PHASE4	COMPLETED	Bioavailability of Bimatoprost Ophthalmic Solution in Human Aqueous.
NCT00386438	PHASE4	COMPLETED	Efficacy of Honan Balloon in Intraocular Pressure Reduction Before Phacoemulsification
NCT00392275	PHASE4	COMPLETED	Penetrance of Third Generation Fluoroquinolones in Eyes With Functioning Filtering Blebs
NCT00428363	PHASE4	COMPLETED	Effect of Optic Edge Design in a Silicone Intraocular Lens on Posterior Capsule Opacification
NCT00449267	PHASE4	COMPLETED	Aurolab Hydrophobic Foldable Intraocular Lens Study
NCT00459303	PHASE4	COMPLETED	Comparison of Functional Vision Provided by AMO Tecnis Z9000 and Alcon SA60AT Acrysof
NCT00469690	PHASE4	COMPLETED	Aqueous Concentrations and PGE2 Inhibition of Ketorolac 0.4% vs. Bromfenac 0.09% in Cataract Patients: Trough Drug Effects
NCT00576485	PHASE4	COMPLETED	Spherical Aberration and Contrast Sensitivity in IOLs
NCT00612729	PHASE4	COMPLETED	Light Filters in Intraocular Lenses (IOLs) and Its Influence on Colour and Contrast Vision.
NCT00612781	PHASE4	COMPLETED	Yellow Versus White Study
NCT00630019	PHASE4	COMPLETED	Ocular Tissue Levels of 1.5% Levofloxacin Ophthalmic Solution Compared to an Active Comparator
NCT00673803	PHASE4	COMPLETED	Influence of Two Different Preloaded Intraocular Lens (IOLs) on Posterior Capsule Opacification
NCT00684138	PHASE4	COMPLETED	ACRYSOF® ReSTOR® Aspheric +3.0 D Add Power Intraocular Lens (IOL)
NCT00698724	PHASE4	COMPLETED	Comparing Optical Coherence Tomography (OCT) and Visual Acuity Outcomes in Subjects Undergoing Cataract Surgery, Who Receive Xibrom Ophthalmic Solution and Standard Presurgical Care vs. Xibrom Ophthalmic Solution Plus Prednisolone Acetate 1% and Standard Presurgical Care
NCT00710905	PHASE4	TERMINATED	Visual Function With Contralateral AcrySof® ReSTOR® Aspheric SN6AD1 and SN6AD3
NCT00710931	PHASE4	COMPLETED	Visual Function With Bilateral AcrySof® ReSTOR® Aspheric SN6AD1
NCT00711347	PHASE4	COMPLETED	Intraoperative Floppy Iris Syndrome
NCT00712244	PHASE4	COMPLETED	DisCoVisc Versus DuoVisc, Healon5 and AmVisc Plus
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00719732	PHASE4	COMPLETED	Visual Function After Implantation of Bilateral AcrySof ReSTOR Aspheric +3
NCT00721253	PHASE4	COMPLETED	Visual Outcomes of Subjects Bilaterally Implanted With ReSTOR Aspheric +4 vs. Tecnis or Acri.LISA
NCT00731640	PHASE4	COMPLETED	Contralateral ReSTOR / Monofocal or Phakic Eye
NCT00732030	PHASE4	COMPLETED	Low Cylinder Toric
NCT00758199	PHASE4	COMPLETED	Determination of Optimum Duration of Treatment With Bromfenac (Xibrom) Eyedrops Following Cataract Surgery
NCT00760058	PHASE4	WITHDRAWN	Visual Outcome and Visual Quality After Bilateral Implantation of the AcrySof® IQ IOL Compared to MI60® and Tecnis® IOL
NCT00760487	PHASE4	COMPLETED	Visual Function After Implantation of Bilateral AcrySof® Toric Natural Intraocular Lens
NCT00761488	PHASE4	WITHDRAWN	Recommendations for Monitoring Clinical Experience Following Implantation of the AcrySof® Toric
NCT00763360	PHASE4	COMPLETED	To Compare the Ability of DiscoVisc® OVD to Protect the Corneal Endothelium and Maintain Anterior Chamber Space With Healon® and Amvisc® PLUS During Cataract Surgery.
NCT00786370	PHASE4	COMPLETED	Dexmedetomidine vs. Propofol for Cataract Surgery
NCT00786565	PHASE4	COMPLETED	Clinical Evaluation of a New Aspheric Intraocular Lens.