TISIDB

Summary
Symbol	GCN1
Name	GCN1 eIF2 alpha kinase activator homolog
Aliases	KIAA0219; GCN1L; GCN1L1; GCN1 (general control of amino-acid synthesis 1, yeast)-like 1; GCN1 general contro ......
Chromosomal Location	12q24.23
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	Cytoplasm Note=Associates with ribosomes in undifferentiated neuroblastoma cells and increases after neuronal differentiation.
Domain	-
Function	Acts as a positive activator of the EIF2AK4/GCN2 protein kinase activity in response to amino acid starvation. Forms a complex with EIF2AK4/GCN2 on translating ribosomes; during this process, GCN1 seems to act as a chaperone to facilitate delivery of uncharged tRNAs that enter the A site of ribosomes to the tRNA-binding domain of EIF2AK4/GCN2, and hence stimulating EIF2AK4/GCN2 kinase activity. Participates in the repression of global protein synthesis and in gene-specific mRNA translation activation, such as the transcriptional activator ATF4, by promoting the EIF2AK4/GCN2-mediated phosphorylation of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52', and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion.

> Gene Ontology [ TOP ]
Biological Process	GO:0006417 regulation of translation GO:0009267 cellular response to starvation GO:0009991 response to extracellular stimulus GO:0010608 posttranscriptional regulation of gene expression GO:0031667 response to nutrient levels GO:0031668 cellular response to extracellular stimulus GO:0031669 cellular response to nutrient levels GO:0033674 positive regulation of kinase activity GO:0034198 cellular response to amino acid starvation GO:0034248 regulation of cellular amide metabolic process GO:0036003 positive regulation of transcription from RNA polymerase II promoter in response to stress GO:0042594 response to starvation GO:0043618 regulation of transcription from RNA polymerase II promoter in response to stress GO:0043620 regulation of DNA-templated transcription in response to stress GO:0071496 cellular response to external stimulus GO:1990253 cellular response to leucine starvation
Molecular Function	GO:0008135 translation factor activity, RNA binding GO:0019207 kinase regulator activity GO:0019887 protein kinase regulator activity GO:0043021 ribonucleoprotein complex binding GO:0043022 ribosome binding GO:0045296 cadherin binding GO:0050839 cell adhesion molecule binding GO:0098631 protein binding involved in cell adhesion GO:0098632 protein binding involved in cell-cell adhesion GO:0098641 cadherin binding involved in cell-cell adhesion
Cellular Component	GO:0005840 ribosome GO:0005844 polysome GO:0005913 cell-cell adherens junction

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	-

Summary
Symbol	GCN1
Name	GCN1 eIF2 alpha kinase activator homolog
Aliases	KIAA0219; GCN1L; GCN1L1; GCN1 (general control of amino-acid synthesis 1, yeast)-like 1; GCN1 general contro ......
Chromosomal Location	12q24.23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between GCN1 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	GCN1
Name	GCN1 eIF2 alpha kinase activator homolog
Aliases	KIAA0219; GCN1L; GCN1L1; GCN1 (general control of amino-acid synthesis 1, yeast)-like 1; GCN1 general contro ......
Chromosomal Location	12q24.23
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 GCN1 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	GCN1
Name	GCN1 eIF2 alpha kinase activator homolog
Aliases	KIAA0219; GCN1L; GCN1L1; GCN1 (general control of amino-acid synthesis 1, yeast)-like 1; GCN1 general contro ......
Chromosomal Location	12q24.23
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 GCN1 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	1
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0	1
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0	1
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	1
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	1
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	1
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0	1
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0	1
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0	1
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.264	0.85
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	1.071	0.579
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.099	0.203

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of GCN1 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	21.4	0	21.4	0.081
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	30	0	30	0.528
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	18.5	2.7	15.8	0.0147
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	18.5	3.4	15.1	0.0291
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	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
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	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	3.7	1.6	1
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	0	7.1	-7.1	0.467
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	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	8.3	-8.3	1

Summary
Symbol	GCN1
Name	GCN1 eIF2 alpha kinase activator homolog
Aliases	KIAA0219; GCN1L; GCN1L1; GCN1 (general control of amino-acid synthesis 1, yeast)-like 1; GCN1 general contro ......
Chromosomal Location	12q24.23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of GCN1. 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	GCN1
Name	GCN1 eIF2 alpha kinase activator homolog
Aliases	KIAA0219; GCN1L; GCN1L1; GCN1 (general control of amino-acid synthesis 1, yeast)-like 1; GCN1 general contro ......
Chromosomal Location	12q24.23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of GCN1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by GCN1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	GCN1
Name	GCN1 eIF2 alpha kinase activator homolog
Aliases	KIAA0219; GCN1L; GCN1L1; GCN1 (general control of amino-acid synthesis 1, yeast)-like 1; GCN1 general contro ......
Chromosomal Location	12q24.23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of GCN1. 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	GCN1
Name	GCN1 eIF2 alpha kinase activator homolog
Aliases	KIAA0219; GCN1L; GCN1L1; GCN1 (general control of amino-acid synthesis 1, yeast)-like 1; GCN1 general contro ......
Chromosomal Location	12q24.23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of GCN1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	GCN1
Name	GCN1 eIF2 alpha kinase activator homolog
Aliases	KIAA0219; GCN1L; GCN1L1; GCN1 (general control of amino-acid synthesis 1, yeast)-like 1; GCN1 general contro ......
Chromosomal Location	12q24.23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between GCN1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	GCN1
Name	GCN1 eIF2 alpha kinase activator homolog
Aliases	KIAA0219; GCN1L; GCN1L1; GCN1 (general control of amino-acid synthesis 1, yeast)-like 1; GCN1 general contro ......
Chromosomal Location	12q24.23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting GCN1 collected from DrugBank database.

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

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