TISIDB

Summary
Symbol	CYBB
Name	cytochrome b-245, beta polypeptide
Aliases	GP91-PHOX; NOX2; CGD; chronic granulomatous disease; AMCBX2; GP91-1; GP91PHOX; IMD34; p91-PHOX; CGD91-phox; ......
Chromosomal Location	Xp21.1
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; Multi-pass membrane protein.
Domain	PF08022 FAD-binding domain PF01794 Ferric reductase like transmembrane component PF08030 Ferric reductase NAD binding domain
Function	Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. It is the terminal component of a respiratory chain that transfers single electrons from cytoplasmic NADPH across the plasma membrane to molecular oxygen on the exterior. Also functions as a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes. It participates in the regulation of cellular pH and is blocked by zinc.

> Gene Ontology [ TOP ]
Biological Process	GO:0000302 response to reactive oxygen species GO:0001101 response to acid chemical GO:0001525 angiogenesis GO:0001666 response to hypoxia GO:0001819 positive regulation of cytokine production GO:0002474 antigen processing and presentation of peptide antigen via MHC class I GO:0002478 antigen processing and presentation of exogenous peptide antigen GO:0002479 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent GO:0006801 superoxide metabolic process GO:0006979 response to oxidative stress GO:0007584 response to nutrient GO:0009991 response to extracellular stimulus GO:0010035 response to inorganic substance GO:0010038 response to metal ion GO:0019882 antigen processing and presentation GO:0019884 antigen processing and presentation of exogenous antigen GO:0031667 response to nutrient levels GO:0031960 response to corticosteroid GO:0032640 tumor necrosis factor production GO:0032680 regulation of tumor necrosis factor production GO:0032760 positive regulation of tumor necrosis factor production GO:0034762 regulation of transmembrane transport GO:0034765 regulation of ion transmembrane transport GO:0036293 response to decreased oxygen levels GO:0036294 cellular response to decreased oxygen levels GO:0042035 regulation of cytokine biosynthetic process GO:0042089 cytokine biosynthetic process GO:0042107 cytokine metabolic process GO:0042108 positive regulation of cytokine biosynthetic process GO:0042493 response to drug GO:0042533 tumor necrosis factor biosynthetic process GO:0042534 regulation of tumor necrosis factor biosynthetic process GO:0042535 positive regulation of tumor necrosis factor biosynthetic process GO:0042554 superoxide anion generation GO:0042590 antigen processing and presentation of exogenous peptide antigen via MHC class I GO:0042743 hydrogen peroxide metabolic process GO:0043200 response to amino acid GO:0043434 response to peptide hormone GO:0045454 cell redox homeostasis GO:0045471 response to ethanol GO:0045730 respiratory burst GO:0045765 regulation of angiogenesis GO:0045766 positive regulation of angiogenesis GO:0046686 response to cadmium ion GO:0048002 antigen processing and presentation of peptide antigen GO:0048010 vascular endothelial growth factor receptor signaling pathway GO:0048514 blood vessel morphogenesis GO:0048545 response to steroid hormone GO:0050665 hydrogen peroxide biosynthetic process GO:0051385 response to mineralocorticoid GO:0070482 response to oxygen levels GO:0071229 cellular response to acid chemical GO:0071230 cellular response to amino acid stimulus GO:0071241 cellular response to inorganic substance GO:0071248 cellular response to metal ion GO:0071276 cellular response to cadmium ion GO:0071361 cellular response to ethanol GO:0071417 cellular response to organonitrogen compound GO:0071453 cellular response to oxygen levels GO:0071456 cellular response to hypoxia GO:0071706 tumor necrosis factor superfamily cytokine production GO:0072593 reactive oxygen species metabolic process GO:0097305 response to alcohol GO:0097306 cellular response to alcohol GO:0097411 hypoxia-inducible factor-1alpha signaling pathway GO:1901342 regulation of vasculature development GO:1901652 response to peptide GO:1901654 response to ketone GO:1903409 reactive oxygen species biosynthetic process GO:1903555 regulation of tumor necrosis factor superfamily cytokine production GO:1903557 positive regulation of tumor necrosis factor superfamily cytokine production GO:1904018 positive regulation of vasculature development GO:1904044 response to aldosterone GO:1904844 response to L-glutamine GO:1904845 cellular response to L-glutamine GO:1990776 response to angiotensin
Molecular Function	GO:0005216 ion channel activity GO:0005244 voltage-gated ion channel activity GO:0009055 electron carrier activity GO:0015267 channel activity GO:0016175 superoxide-generating NADPH oxidase activity GO:0016651 oxidoreductase activity, acting on NAD(P)H GO:0020037 heme binding GO:0022803 passive transmembrane transporter activity GO:0022832 voltage-gated channel activity GO:0022836 gated channel activity GO:0022838 substrate-specific channel activity GO:0046906 tetrapyrrole binding GO:0046982 protein heterodimerization activity GO:0048037 cofactor binding GO:0050660 flavin adenine dinucleotide binding GO:0050662 coenzyme binding GO:0050664 oxidoreductase activity, acting on NAD(P)H, oxygen as acceptor
Cellular Component	GO:0005635 nuclear envelope GO:0005791 rough endoplasmic reticulum GO:0030139 endocytic vesicle GO:0030425 dendrite GO:0030659 cytoplasmic vesicle membrane GO:0030666 endocytic vesicle membrane GO:0030670 phagocytic vesicle membrane GO:0043020 NADPH oxidase complex GO:0043025 neuronal cell body GO:0044297 cell body GO:0045335 phagocytic vesicle GO:1990204 oxidoreductase complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04066 HIF-1 signaling pathway hsa04145 Phagosome hsa04621 NOD-like receptor signaling pathway hsa04670 Leukocyte transendothelial migration
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-1236975: Antigen processing-Cross presentation R-HSA-2262752: Cellular responses to stress R-HSA-983169: Class I MHC mediated antigen processing & presentation R-HSA-1236973: Cross-presentation of particulate exogenous antigens (phagosomes) R-HSA-3299685: Detoxification of Reactive Oxygen Species R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-6798695: Neutrophil degranulation R-HSA-195258: RHO GTPase Effectors R-HSA-5668599: RHO GTPases Activate NADPH Oxidases R-HSA-1222556: ROS, RNS production in phagocytes R-HSA-162582: Signal Transduction R-HSA-194315: Signaling by Rho GTPases R-HSA-194138: Signaling by VEGF R-HSA-4420097: VEGFA-VEGFR2 Pathway

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04066 HIF-1 signaling pathway
hsa04145 Phagosome
hsa04621 NOD-like receptor signaling pathway
hsa04670 Leukocyte transendothelial migration

Reactome

R-HSA-1280218: Adaptive Immune System
R-HSA-1236975: Antigen processing-Cross presentation
R-HSA-2262752: Cellular responses to stress
R-HSA-983169: Class I MHC mediated antigen processing & presentation
R-HSA-1236973: Cross-presentation of particulate exogenous antigens (phagosomes)
R-HSA-3299685: Detoxification of Reactive Oxygen Species
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-6798695: Neutrophil degranulation
R-HSA-195258: RHO GTPase Effectors
R-HSA-5668599: RHO GTPases Activate NADPH Oxidases
R-HSA-1222556: ROS, RNS production in phagocytes
R-HSA-162582: Signal Transduction
R-HSA-194315: Signaling by Rho GTPases
R-HSA-194138: Signaling by VEGF
R-HSA-4420097: VEGFA-VEGFR2 Pathway

Summary
Symbol	CYBB
Name	cytochrome b-245, beta polypeptide
Aliases	GP91-PHOX; NOX2; CGD; chronic granulomatous disease; AMCBX2; GP91-1; GP91PHOX; IMD34; p91-PHOX; CGD91-phox; ......
Chromosomal Location	Xp21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CYBB 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 CYBB and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
19380816	Head and neck squamous cell carcinoma	Inhibit immunity (T cell function)	The increased ROS production by MDSC is mediated by up-regulated activity of NADPH oxidase (NOX2). MDSC from tumor-bearing mice had significantly higher expression of NOX2 subunits, primarily p47(phox) and gp91(phox), compared with immature myeloid cells from tumor-free mice. Expression of NOX2 subunits in MDSC was controlled by the STAT3 transcription factor. In the absence of NOX2 activity, MDSC lost the ability to suppress T cell responses and quickly differentiated into mature macrophages and dendritic cells.
28292946	Chronic Myelomonocytic Leukemia	Inhibit immunity (T cell function)	The dominant population of primary human CMML cells was found to express membrane-bound NOX2 and to release ROS, which, in turn, triggered extensive PARP-1-dependent cell death in cocultured NK cells, CD8+ T effector memory cells, and CD8+ T effector cells. Inhibitors of ROS formation and scavengers of extracellular ROS prevented CMML cell-induced lymphocyte death and facilitated NK cell degranulation toward Ab-coated, primary CMML cells. In patients with CMML, elevation of immature cell counts (CD34+) in blood was associated with reduced expression of several NK cell-activating receptors.
29602801	mesothelioma	Inhibit immunity (T cell function)	Culture of healthy-donor granulocytes with human mesothelioma cells showed that GM-CSF upregulates NOX2 expression and the release of reactive oxygen species (ROS) from granulocytes, resulting in T-cell suppression.

Summary
Symbol	CYBB
Name	cytochrome b-245, beta polypeptide
Aliases	GP91-PHOX; NOX2; CGD; chronic granulomatous disease; AMCBX2; GP91-1; GP91PHOX; IMD34; p91-PHOX; CGD91-phox; ......
Chromosomal Location	Xp21.1
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 CYBB 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	CYBB
Name	cytochrome b-245, beta polypeptide
Aliases	GP91-PHOX; NOX2; CGD; chronic granulomatous disease; AMCBX2; GP91-1; GP91PHOX; IMD34; p91-PHOX; CGD91-phox; ......
Chromosomal Location	Xp21.1
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 CYBB 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	-0.094	0.86
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.213	0.915
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.324	0.838
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.967	0.225
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.166	0.917
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	2.418	0.304
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.327	0.54
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.769	0.695
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.168	0.939
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.405	0.397
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	1.776	0.504
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.007	0.968

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CYBB 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	4.1	-4.1	0.561
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	5.1	-5.1	0.549
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	14.3	5.9	8.4	0.613
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	15.4	9.1	6.3	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	0	0	0	1
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	CYBB
Name	cytochrome b-245, beta polypeptide
Aliases	GP91-PHOX; NOX2; CGD; chronic granulomatous disease; AMCBX2; GP91-1; GP91PHOX; IMD34; p91-PHOX; CGD91-phox; ......
Chromosomal Location	Xp21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CYBB. 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	CYBB
Name	cytochrome b-245, beta polypeptide
Aliases	GP91-PHOX; NOX2; CGD; chronic granulomatous disease; AMCBX2; GP91-1; GP91PHOX; IMD34; p91-PHOX; CGD91-phox; ......
Chromosomal Location	Xp21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CYBB. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CYBB. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CYBB
Name	cytochrome b-245, beta polypeptide
Aliases	GP91-PHOX; NOX2; CGD; chronic granulomatous disease; AMCBX2; GP91-1; GP91PHOX; IMD34; p91-PHOX; CGD91-phox; ......
Chromosomal Location	Xp21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CYBB. 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	CYBB
Name	cytochrome b-245, beta polypeptide
Aliases	GP91-PHOX; NOX2; CGD; chronic granulomatous disease; AMCBX2; GP91-1; GP91PHOX; IMD34; p91-PHOX; CGD91-phox; ......
Chromosomal Location	Xp21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CYBB expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CYBB
Name	cytochrome b-245, beta polypeptide
Aliases	GP91-PHOX; NOX2; CGD; chronic granulomatous disease; AMCBX2; GP91-1; GP91PHOX; IMD34; p91-PHOX; CGD91-phox; ......
Chromosomal Location	Xp21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CYBB and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CYBB
Name	cytochrome b-245, beta polypeptide
Aliases	GP91-PHOX; NOX2; CGD; chronic granulomatous disease; AMCBX2; GP91-1; GP91PHOX; IMD34; p91-PHOX; CGD91-phox; ......
Chromosomal Location	Xp21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CYBB collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CYBB.

ID	Name	Drug Type	Targets	#Targets
DB00514	Dextromethorphan	Small Molecule	CHRNA2, CHRNA3, CHRNA4, CHRNA7, CHRNB2, CHRNB4, CYBA, CYBB, GRIN3A ......	21

Browse CYBB