TISIDB

Summary
Symbol	ROR1
Name	receptor tyrosine kinase-like orphan receptor 1
Aliases	NTRKR1; dJ537F10.1; neurotrophic tyrosine kinase, receptor-related 1; Inactive tyrosine-protein kinase trans ......
Chromosomal Location	1p31.3
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	Membrane Single-pass type I membrane protein. Cell projection, axon
Domain	PF01392 Fz domain PF07679 Immunoglobulin I-set domain PF00051 Kringle domain PF07714 Protein tyrosine kinase
Function	Has very low kinase activity in vitro and is unlikely to function as a tyrosine kinase in vivo (PubMed:25029443). Receptor for ligand WNT5A which activate downstream NFkB signaling pathway and may result in the inhibition of WNT3A-mediated signaling (PubMed:25029443, PubMed:27162350). In inner ear, crucial for spiral ganglion neurons to innervate auditory hair cells (PubMed:27162350).

> Gene Ontology [ TOP ]
Biological Process	GO:0001736 establishment of planar polarity GO:0001738 morphogenesis of a polarized epithelium GO:0007164 establishment of tissue polarity GO:0016055 Wnt signaling pathway GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0035567 non-canonical Wnt signaling pathway GO:0060071 Wnt signaling pathway, planar cell polarity pathway GO:0090175 regulation of establishment of planar polarity GO:0198738 cell-cell signaling by wnt GO:1905330 regulation of morphogenesis of an epithelium GO:2000027 regulation of organ morphogenesis
Molecular Function	GO:0004713 protein tyrosine kinase activity GO:0004714 transmembrane receptor protein tyrosine kinase activity GO:0015026 coreceptor activity GO:0017147 Wnt-protein binding GO:0019199 transmembrane receptor protein kinase activity GO:0071936 coreceptor activity involved in Wnt signaling pathway GO:1904929 coreceptor activity involved in Wnt signaling pathway, planar cell polarity pathway
Cellular Component	GO:0043235 receptor complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-3858494: Beta-catenin independent WNT signaling R-HSA-4086400: PCP/CE pathway R-HSA-162582: Signal Transduction R-HSA-195721: Signaling by Wnt R-HSA-5140745: WNT5A-dependent internalization of FZD2, FZD5 and ROR2

Summary
Symbol	ROR1
Name	receptor tyrosine kinase-like orphan receptor 1
Aliases	NTRKR1; dJ537F10.1; neurotrophic tyrosine kinase, receptor-related 1; Inactive tyrosine-protein kinase trans ......
Chromosomal Location	1p31.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ROR1 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 ROR1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
18287027	Chronic Lymphocytic Leukemia	Promote immunity (T cell function)	Antisera induced by infusions of autologous Ad-CD154-leukemia B cells identify ROR1 as an oncofetal antigen and receptor for Wnt5a Five patients made high-titer antibodies against adenovirus and three made IgG reactive with a leukemia-associated surface antigen, which we identified as ROR1.
28465528	Chronic Lymphocytic Leukemia	Inhibit immunity (T cell function); essential for immunotherapy	Wnt5a induces ROR1 to associate with 14-3-3ζ for enhanced chemotaxis and proliferation of chronic lymphocytic leukemia cells. Wnt5a can activate Rho GTPases in chronic lymphocytic leukemia (CLL) cells by inducing the recruitment of ARHGEF2 to ROR1. The capacity of Wnt5a to induce ROR1 to complex with 14-3-3ζ could be blocked in CLL cells by treatment with cirmtuzumab, a humanized mAb targeting ROR1.
22289919	Chronic Lymphocytic Leukemia	Inhibit immunity	A significantly higher frequency of ROR1 expression was found in patients with progressive versus non-progressive disease, and in those with unmutated versus mutated IgVH genes. Cross-linking of anti-ROR1 MAbs using the F(ab')(2) fragments of anti-Fc antibodies significantly augmented apoptosis. Two of the MAbs induced complement-dependent cytotoxicity (CDC) similar to that of rituximab and one anti-ROR1 MAb (KNG) (IgG1) showed killing activity by antibody-dependent cellular cytotoxicity.

Summary
Symbol	ROR1
Name	receptor tyrosine kinase-like orphan receptor 1
Aliases	NTRKR1; dJ537F10.1; neurotrophic tyrosine kinase, receptor-related 1; Inactive tyrosine-protein kinase trans ......
Chromosomal Location	1p31.3
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 ROR1 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	ROR1
Name	receptor tyrosine kinase-like orphan receptor 1
Aliases	NTRKR1; dJ537F10.1; neurotrophic tyrosine kinase, receptor-related 1; Inactive tyrosine-protein kinase trans ......
Chromosomal Location	1p31.3
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 ROR1 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	0.029	0.922
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.753	0.253
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.501	0.355
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.814	0.113
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.546	0.736
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-1.152	0.565
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.798	0.195
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.842	0.459
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.806	0.5
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.328	0.638
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	1.151	0.188
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.49	0.0131

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ROR1 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	2.7	-2.7	1
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	3.4	-3.4	1
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	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	9.1	-1.4	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
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	10.5	0	10.5	0.135
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	12.5	0	12.5	0.485
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	7.7	-7.7	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	100	-100	0.143
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	ROR1
Name	receptor tyrosine kinase-like orphan receptor 1
Aliases	NTRKR1; dJ537F10.1; neurotrophic tyrosine kinase, receptor-related 1; Inactive tyrosine-protein kinase trans ......
Chromosomal Location	1p31.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ROR1. 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	ROR1
Name	receptor tyrosine kinase-like orphan receptor 1
Aliases	NTRKR1; dJ537F10.1; neurotrophic tyrosine kinase, receptor-related 1; Inactive tyrosine-protein kinase trans ......
Chromosomal Location	1p31.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ROR1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ROR1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ROR1
Name	receptor tyrosine kinase-like orphan receptor 1
Aliases	NTRKR1; dJ537F10.1; neurotrophic tyrosine kinase, receptor-related 1; Inactive tyrosine-protein kinase trans ......
Chromosomal Location	1p31.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ROR1. 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	ROR1
Name	receptor tyrosine kinase-like orphan receptor 1
Aliases	NTRKR1; dJ537F10.1; neurotrophic tyrosine kinase, receptor-related 1; Inactive tyrosine-protein kinase trans ......
Chromosomal Location	1p31.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ROR1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ROR1
Name	receptor tyrosine kinase-like orphan receptor 1
Aliases	NTRKR1; dJ537F10.1; neurotrophic tyrosine kinase, receptor-related 1; Inactive tyrosine-protein kinase trans ......
Chromosomal Location	1p31.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ROR1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ROR1
Name	receptor tyrosine kinase-like orphan receptor 1
Aliases	NTRKR1; dJ537F10.1; neurotrophic tyrosine kinase, receptor-related 1; Inactive tyrosine-protein kinase trans ......
Chromosomal Location	1p31.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ROR1 collected from DrugBank database.

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

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