TISIDB

Summary
Symbol	COL18A1
Name	collagen, type XVIII, alpha 1
Aliases	KNO1; endostatin; KNO; Knobloch syndrome, type 1; antiangiogenic agent; multi-functional protein MFP; Collag ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Secreted, extracellular space, extracellular matrix Secreted, extracellular space, extracellular matrix, basement membrane ; SUBCELLULAR LOCATION: Non-collagenous domain 1: Secreted, extracellular space, extracellular matrix, basement membrane Secreted ; SUBCELLULAR LOCATION: Endostatin: Secreted Secreted, extracellular space, extracellular matrix, basement membrane
Domain	PF01391 Collagen triple helix repeat (20 copies) PF06121 Domain of Unknown Function (DUF959) PF06482 Collagenase NC10 and Endostatin PF01392 Fz domain
Function	Probably plays a major role in determining the retinal structure as well as in the closure of the neural tube. ; FUNCTION: Non-collagenous domain 1: May regulate extracellular matrix-dependent motility and morphogenesis of endothelial and non-endothelial cells; the function requires homotrimerization and implicates MAPK signaling. ; FUNCTION: Endostatin: Potently inhibits endothelial cell proliferation and angiogenesis (PubMed:9459295). May inhibit angiogenesis by binding to the heparan sulfate proteoglycans involved in growth factor signaling (By similarity). 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 (By similarity). May negatively regulate the activity of homotrimeric non-collagenous domain 1 (PubMed:11257123).

> Gene Ontology [ TOP ]
Biological Process	GO:0001101 response to acid chemical GO:0001525 angiogenesis GO:0001885 endothelial cell development GO:0001886 endothelial cell morphogenesis GO:0002064 epithelial cell development GO:0003158 endothelium development GO:0003382 epithelial cell morphogenesis GO:0007601 visual perception GO:0009415 response to water GO:0010035 response to inorganic substance GO:0030198 extracellular matrix organization GO:0030335 positive regulation of cell migration GO:0030574 collagen catabolic process GO:0032963 collagen metabolic process GO:0040017 positive regulation of locomotion GO:0042493 response to drug GO:0043062 extracellular structure organization GO:0044236 multicellular organism metabolic process GO:0044243 multicellular organism catabolic process GO:0044259 multicellular organismal macromolecule metabolic process GO:0045446 endothelial cell differentiation GO:0048514 blood vessel morphogenesis GO:0050953 sensory perception of light stimulus GO:0051272 positive regulation of cellular component movement GO:0051599 response to hydrostatic pressure GO:0072577 endothelial cell apoptotic process GO:1904019 epithelial cell apoptotic process GO:1904035 regulation of epithelial cell apoptotic process GO:1904037 positive regulation of epithelial cell apoptotic process GO:2000147 positive regulation of cell motility GO:2000351 regulation of endothelial cell apoptotic process GO:2000353 positive regulation of endothelial cell apoptotic process
Molecular Function	-
Cellular Component	GO:0005578 proteinaceous extracellular matrix GO:0005581 collagen trimer GO:0005604 basement membrane GO:0005788 endoplasmic reticulum lumen GO:0044420 extracellular matrix component

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04974 Protein digestion and absorption
Reactome	R-HSA-1592389: Activation of Matrix Metalloproteinases R-HSA-2022090: Assembly of collagen fibrils and other multimeric structures R-HSA-1650814: Collagen biosynthesis and modifying enzymes R-HSA-8948216: Collagen chain trimerization R-HSA-1442490: Collagen degradation R-HSA-1474290: Collagen formation R-HSA-1474228: Degradation of the extracellular matrix R-HSA-1474244: Extracellular matrix organization R-HSA-216083: Integrin cell surface interactions R-HSA-3000157: Laminin interactions

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04974 Protein digestion and absorption

Reactome

R-HSA-1592389: Activation of Matrix Metalloproteinases
R-HSA-2022090: Assembly of collagen fibrils and other multimeric structures
R-HSA-1650814: Collagen biosynthesis and modifying enzymes
R-HSA-8948216: Collagen chain trimerization
R-HSA-1442490: Collagen degradation
R-HSA-1474290: Collagen formation
R-HSA-1474228: Degradation of the extracellular matrix
R-HSA-1474244: Extracellular matrix organization
R-HSA-216083: Integrin cell surface interactions
R-HSA-3000157: Laminin interactions

Summary
Symbol	COL18A1
Name	collagen, type XVIII, alpha 1
Aliases	KNO1; endostatin; KNO; Knobloch syndrome, type 1; antiangiogenic agent; multi-functional protein MFP; Collag ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between COL18A1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between COL18A1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
17513560	Renal Cell Carcinoma	Promote immunity	Anti-tumor effect of endostatin mediated by retroviral gene transfer in mice bearing renal cell carcinoma. In conclusion, retroviral endostatin gene transfer led to secretion of functional endostatin that was sufficiently active to inhibit tumor angiogenesis and tumor growth.

Summary
Symbol	COL18A1
Name	collagen, type XVIII, alpha 1
Aliases	KNO1; endostatin; KNO; Knobloch syndrome, type 1; antiangiogenic agent; multi-functional protein MFP; Collag ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of COL18A1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	COL18A1
Name	collagen, type XVIII, alpha 1
Aliases	KNO1; endostatin; KNO; Knobloch syndrome, type 1; antiangiogenic agent; multi-functional protein MFP; Collag ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of COL18A1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.748	0.0642
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.741	0.517
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.02	0.992
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.14	0.764
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.357	0.91
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.138	0.972
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.583	0.322
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.345	0.847
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.742	0.727
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.082	0.97
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.616	0.842
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.376	0.00603

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of COL18A1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	6.8	-6.8	0.32
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	8.5	-8.5	0.32
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	16.7	-16.7	0.429
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	22.2	6.2	16	0.53
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	40	11.1	28.9	0.505
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	7.9	0	7.9	0.26
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	COL18A1
Name	collagen, type XVIII, alpha 1
Aliases	KNO1; endostatin; KNO; Knobloch syndrome, type 1; antiangiogenic agent; multi-functional protein MFP; Collag ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of COL18A1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	COL18A1
Name	collagen, type XVIII, alpha 1
Aliases	KNO1; endostatin; KNO; Knobloch syndrome, type 1; antiangiogenic agent; multi-functional protein MFP; Collag ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of COL18A1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by COL18A1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	COL18A1
Name	collagen, type XVIII, alpha 1
Aliases	KNO1; endostatin; KNO; Knobloch syndrome, type 1; antiangiogenic agent; multi-functional protein MFP; Collag ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of COL18A1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	COL18A1
Name	collagen, type XVIII, alpha 1
Aliases	KNO1; endostatin; KNO; Knobloch syndrome, type 1; antiangiogenic agent; multi-functional protein MFP; Collag ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of COL18A1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	COL18A1
Name	collagen, type XVIII, alpha 1
Aliases	KNO1; endostatin; KNO; Knobloch syndrome, type 1; antiangiogenic agent; multi-functional protein MFP; Collag ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between COL18A1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	COL18A1
Name	collagen, type XVIII, alpha 1
Aliases	KNO1; endostatin; KNO; Knobloch syndrome, type 1; antiangiogenic agent; multi-functional protein MFP; Collag ......
Chromosomal Location	21q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting COL18A1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

Browse COL18A1