TISIDB

Summary
Symbol	GFRA2
Name	GDNF family receptor alpha 2
Aliases	RETL2; GDNFRB; NTNRA; TRNR2; NRTNR-ALPHA; GDNF receptor beta; GDNFR-alpha-2; GDNFR-beta; GFR-alpha 2; NTNR-a ......
Chromosomal Location	8p21.3
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	Cell membrane Lipid-anchor, GPI-anchor
Domain	PF02351 GDNF/GAS1 domain
Function	Receptor for neurturin. Mediates the NRTN-induced autophosphorylation and activation of the RET receptor. Also able to mediate GDNF signaling through the RET tyrosine kinase receptor.; FUNCTION: Isoform 2: participates in NRTN-induced 'Ser-727' phosphorylation of STAT3.

> Gene Ontology [ TOP ]
Biological Process	GO:0001933 negative regulation of protein phosphorylation GO:0007259 JAK-STAT cascade GO:0018105 peptidyl-serine phosphorylation GO:0018209 peptidyl-serine modification GO:0031952 regulation of protein autophosphorylation GO:0031953 negative regulation of protein autophosphorylation GO:0033135 regulation of peptidyl-serine phosphorylation GO:0033136 serine phosphorylation of STAT3 protein GO:0033138 positive regulation of peptidyl-serine phosphorylation GO:0033139 regulation of peptidyl-serine phosphorylation of STAT protein GO:0033141 positive regulation of peptidyl-serine phosphorylation of STAT protein GO:0035860 glial cell-derived neurotrophic factor receptor signaling pathway GO:0042326 negative regulation of phosphorylation GO:0042501 serine phosphorylation of STAT protein GO:0046425 regulation of JAK-STAT cascade GO:0046777 protein autophosphorylation GO:0097696 STAT cascade GO:1903261 regulation of serine phosphorylation of STAT3 protein GO:1903263 positive regulation of serine phosphorylation of STAT3 protein GO:1904892 regulation of STAT cascade
Molecular Function	GO:0004896 cytokine receptor activity GO:0005085 guanyl-nucleotide exchange factor activity GO:0005088 Ras guanyl-nucleotide exchange factor activity GO:0016167 glial cell-derived neurotrophic factor receptor activity
Cellular Component	GO:0019898 extrinsic component of membrane GO:0031225 anchored component of membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-170984: ARMS-mediated activation R-HSA-422475: Axon guidance R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-2172127: DAP12 interactions R-HSA-2424491: DAP12 signaling R-HSA-1266738: Developmental Biology R-HSA-186763: Downstream signal transduction R-HSA-2871796: FCERI mediated MAPK activation R-HSA-2454202: Fc epsilon receptor (FCERI) signaling R-HSA-170968: Frs2-mediated activation R-HSA-179812: GRB2 events in EGFR signaling R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK R-HSA-2428924: IGF1R signaling cascade R-HSA-112399: IRS-mediated signalling R-HSA-2428928: IRS-related events triggered by IGF1R R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-74751: Insulin receptor signalling cascade R-HSA-912526: Interleukin receptor SHC signaling R-HSA-451927: Interleukin-2 signaling R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling R-HSA-5683057: MAPK family signaling cascades R-HSA-5684996: MAPK1/MAPK3 signaling R-HSA-375165: NCAM signaling for neurite out-growth R-HSA-419037: NCAM1 interactions R-HSA-187037: NGF signalling via TRKA from the plasma membrane R-HSA-169893: Prolonged ERK activation events R-HSA-5673001: RAF/MAP kinase cascade R-HSA-8853659: RET signaling R-HSA-180336: SHC1 events in EGFR signaling R-HSA-112412: SOS-mediated signalling R-HSA-162582: Signal Transduction R-HSA-177929: Signaling by EGFR R-HSA-372790: Signaling by GPCR R-HSA-74752: Signaling by Insulin receptor R-HSA-449147: Signaling by Interleukins R-HSA-2586552: Signaling by Leptin R-HSA-186797: Signaling by PDGF R-HSA-1433557: Signaling by SCF-KIT R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) R-HSA-194138: Signaling by VEGF R-HSA-166520: Signalling by NGF R-HSA-187687: Signalling to ERKs R-HSA-167044: Signalling to RAS R-HSA-187706: Signalling to p38 via RIT and RIN R-HSA-4420097: VEGFA-VEGFR2 Pathway R-HSA-5218921: VEGFR2 mediated cell proliferation

> KEGG and Reactome Pathway

[ TOP ]

KEGG

Reactome

R-HSA-170984: ARMS-mediated activation
R-HSA-422475: Axon guidance
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-1266738: Developmental Biology
R-HSA-186763: Downstream signal transduction
R-HSA-2871796: FCERI mediated MAPK activation
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-170968: Frs2-mediated activation
R-HSA-179812: GRB2 events in EGFR signaling
R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-2428924: IGF1R signaling cascade
R-HSA-112399: IRS-mediated signalling
R-HSA-2428928: IRS-related events triggered by IGF1R
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-74751: Insulin receptor signalling cascade
R-HSA-912526: Interleukin receptor SHC signaling
R-HSA-451927: Interleukin-2 signaling
R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling
R-HSA-5683057: MAPK family signaling cascades
R-HSA-5684996: MAPK1/MAPK3 signaling
R-HSA-375165: NCAM signaling for neurite out-growth
R-HSA-419037: NCAM1 interactions
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-169893: Prolonged ERK activation events
R-HSA-5673001: RAF/MAP kinase cascade
R-HSA-8853659: RET signaling
R-HSA-180336: SHC1 events in EGFR signaling
R-HSA-112412: SOS-mediated signalling
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-372790: Signaling by GPCR
R-HSA-74752: Signaling by Insulin receptor
R-HSA-449147: Signaling by Interleukins
R-HSA-2586552: Signaling by Leptin
R-HSA-186797: Signaling by PDGF
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-194138: Signaling by VEGF
R-HSA-166520: Signalling by NGF
R-HSA-187687: Signalling to ERKs
R-HSA-167044: Signalling to RAS
R-HSA-187706: Signalling to p38 via RIT and RIN
R-HSA-4420097: VEGFA-VEGFR2 Pathway
R-HSA-5218921: VEGFR2 mediated cell proliferation

Summary
Symbol	GFRA2
Name	GDNF family receptor alpha 2
Aliases	RETL2; GDNFRB; NTNRA; TRNR2; NRTNR-ALPHA; GDNF receptor beta; GDNFR-alpha-2; GDNFR-beta; GFR-alpha 2; NTNR-a ......
Chromosomal Location	8p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between GFRA2 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 [ TOP ]
There is no record.

Summary
Symbol	GFRA2
Name	GDNF family receptor alpha 2
Aliases	RETL2; GDNFRB; NTNRA; TRNR2; NRTNR-ALPHA; GDNF receptor beta; GDNFR-alpha-2; GDNFR-beta; GFR-alpha 2; NTNR-a ......
Chromosomal Location	8p21.3
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

[ TOP ]

Statistical results of GFRA2 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	GFRA2
Name	GDNF family receptor alpha 2
Aliases	RETL2; GDNFRB; NTNRA; TRNR2; NRTNR-ALPHA; GDNF receptor beta; GDNFR-alpha-2; GDNFR-beta; GFR-alpha 2; NTNR-a ......
Chromosomal Location	8p21.3
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

[ TOP ]

Points in the above scatter plot represent the expression difference of GFRA2 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	-0.592	0.166
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.373	0.596
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.74	0.212
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.497	0.375
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.114	0.926
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.977	0.527
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.252	0.652
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.096	0.908
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.687	0.437
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.277	0.672
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	-0.896	0.279
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.642	0.00162

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of GFRA2 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	1.4	-1.4	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	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	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	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	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	GFRA2
Name	GDNF family receptor alpha 2
Aliases	RETL2; GDNFRB; NTNRA; TRNR2; NRTNR-ALPHA; GDNF receptor beta; GDNFR-alpha-2; GDNFR-beta; GFR-alpha 2; NTNR-a ......
Chromosomal Location	8p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of GFRA2. 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	GFRA2
Name	GDNF family receptor alpha 2
Aliases	RETL2; GDNFRB; NTNRA; TRNR2; NRTNR-ALPHA; GDNF receptor beta; GDNFR-alpha-2; GDNFR-beta; GFR-alpha 2; NTNR-a ......
Chromosomal Location	8p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of GFRA2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by GFRA2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	GFRA2
Name	GDNF family receptor alpha 2
Aliases	RETL2; GDNFRB; NTNRA; TRNR2; NRTNR-ALPHA; GDNF receptor beta; GDNFR-alpha-2; GDNFR-beta; GFR-alpha 2; NTNR-a ......
Chromosomal Location	8p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of GFRA2. 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	GFRA2
Name	GDNF family receptor alpha 2
Aliases	RETL2; GDNFRB; NTNRA; TRNR2; NRTNR-ALPHA; GDNF receptor beta; GDNFR-alpha-2; GDNFR-beta; GFR-alpha 2; NTNR-a ......
Chromosomal Location	8p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of GFRA2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	GFRA2
Name	GDNF family receptor alpha 2
Aliases	RETL2; GDNFRB; NTNRA; TRNR2; NRTNR-ALPHA; GDNF receptor beta; GDNFR-alpha-2; GDNFR-beta; GFR-alpha 2; NTNR-a ......
Chromosomal Location	8p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between GFRA2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	GFRA2
Name	GDNF family receptor alpha 2
Aliases	RETL2; GDNFRB; NTNRA; TRNR2; NRTNR-ALPHA; GDNF receptor beta; GDNFR-alpha-2; GDNFR-beta; GFR-alpha 2; NTNR-a ......
Chromosomal Location	8p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting GFRA2 collected from DrugBank database.

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

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