TISIDB

Summary
Symbol	PIK3C3
Name	phosphatidylinositol 3-kinase, catalytic subunit type 3
Aliases	Vps34; phosphoinositide-3-kinase, class 3; hVps34; PI3-kinase type 3; PI3K type 3; PtdIns-3-kinase type 3; p ......
Chromosomal Location	18q12.3
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	Midbody Late endosome Cytoplasmic vesicle, autophagosome Note=As component of the PI3K complex I localized to pre-autophagosome structures. As component of the PI3K complex II localized predominantly to endosomes (Probable). Localizes also to discrete punctae along the ciliary axoneme and to the base of the ciliary axoneme (By similarity).
Domain	PF00454 Phosphatidylinositol 3- and 4-kinase PF00792 Phosphoinositide 3-kinase C2 PF00613 Phosphoinositide 3-kinase family
Function	Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123, PubMed:20208530). Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for transport from early to late endosomes (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0000045 autophagosome assembly GO:0000910 cytokinesis GO:0001101 response to acid chemical GO:0002218 activation of innate immune response GO:0002221 pattern recognition receptor signaling pathway GO:0002224 toll-like receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0006497 protein lipidation GO:0006644 phospholipid metabolic process GO:0006650 glycerophospholipid metabolic process GO:0006661 phosphatidylinositol biosynthetic process GO:0006914 autophagy GO:0007032 endosome organization GO:0007033 vacuole organization GO:0007034 vacuolar transport GO:0008654 phospholipid biosynthetic process GO:0009267 cellular response to starvation GO:0009306 protein secretion GO:0009991 response to extracellular stimulus GO:0016197 endosomal transport GO:0016236 macroautophagy GO:0016482 cytosolic transport GO:0016485 protein processing GO:0030258 lipid modification GO:0031349 positive regulation of defense response GO:0031667 response to nutrient levels GO:0031668 cellular response to extracellular stimulus GO:0031669 cellular response to nutrient levels GO:0032465 regulation of cytokinesis GO:0034162 toll-like receptor 9 signaling pathway GO:0034497 protein localization to pre-autophagosomal structure GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process GO:0042149 cellular response to glucose starvation GO:0042157 lipoprotein metabolic process GO:0042158 lipoprotein biosynthetic process GO:0042594 response to starvation GO:0043200 response to amino acid GO:0043201 response to leucine GO:0045017 glycerolipid biosynthetic process GO:0045022 early endosome to late endosome transport GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0046474 glycerophospholipid biosynthetic process GO:0046486 glycerolipid metabolic process GO:0046488 phosphatidylinositol metabolic process GO:0046834 lipid phosphorylation GO:0046854 phosphatidylinositol phosphorylation GO:0048015 phosphatidylinositol-mediated signaling GO:0048017 inositol lipid-mediated signaling GO:0050708 regulation of protein secretion GO:0051302 regulation of cell division GO:0051604 protein maturation GO:0071496 cellular response to external stimulus GO:0098927 vesicle-mediated transport between endosomal compartments GO:1905037 autophagosome organization
Molecular Function	GO:0016303 1-phosphatidylinositol-3-kinase activity GO:0035004 phosphatidylinositol 3-kinase activity GO:0052742 phosphatidylinositol kinase activity
Cellular Component	GO:0005767 secondary lysosome GO:0005770 late endosome GO:0005776 autophagosome GO:0005929 cilium GO:0005930 axoneme GO:0005942 phosphatidylinositol 3-kinase complex GO:0019898 extrinsic component of membrane GO:0030139 endocytic vesicle GO:0030496 midbody GO:0030659 cytoplasmic vesicle membrane GO:0030666 endocytic vesicle membrane GO:0030670 phagocytic vesicle membrane GO:0035032 phosphatidylinositol 3-kinase complex, class III GO:0044441 ciliary part GO:0044754 autolysosome GO:0045335 phagocytic vesicle GO:0061695 transferase complex, transferring phosphorus-containing groups GO:0097014 ciliary plasm

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04070 Phosphatidylinositol signaling system hsa04140 Regulation of autophagy hsa04145 Phagosome hsa00562 Inositol phosphate metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-2262752: Cellular responses to stress 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-1632852: Macroautophagy R-HSA-1430728: Metabolism R-HSA-556833: Metabolism of lipids and lipoproteins R-HSA-1483255: PI Metabolism R-HSA-109704: PI3K Cascade R-HSA-1483257: Phospholipid metabolism R-HSA-195258: RHO GTPase Effectors R-HSA-5668599: RHO GTPases Activate NADPH Oxidases R-HSA-162582: Signal Transduction R-HSA-74752: Signaling by Insulin receptor R-HSA-194315: Signaling by Rho GTPases R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) R-HSA-1660514: Synthesis of PIPs at the Golgi membrane R-HSA-1660516: Synthesis of PIPs at the early endosome membrane R-HSA-1660517: Synthesis of PIPs at the late endosome membrane R-HSA-168138: Toll Like Receptor 9 (TLR9) Cascade R-HSA-168898: Toll-Like Receptors Cascades

> KEGG and Reactome Pathway

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KEGG

hsa04070 Phosphatidylinositol signaling system
hsa04140 Regulation of autophagy
hsa04145 Phagosome
hsa00562 Inositol phosphate metabolism
hsa01100 Metabolic pathways

Reactome

R-HSA-2262752: Cellular responses to stress
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-1632852: Macroautophagy
R-HSA-1430728: Metabolism
R-HSA-556833: Metabolism of lipids and lipoproteins
R-HSA-1483255: PI Metabolism
R-HSA-109704: PI3K Cascade
R-HSA-1483257: Phospholipid metabolism
R-HSA-195258: RHO GTPase Effectors
R-HSA-5668599: RHO GTPases Activate NADPH Oxidases
R-HSA-162582: Signal Transduction
R-HSA-74752: Signaling by Insulin receptor
R-HSA-194315: Signaling by Rho GTPases
R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-1660514: Synthesis of PIPs at the Golgi membrane
R-HSA-1660516: Synthesis of PIPs at the early endosome membrane
R-HSA-1660517: Synthesis of PIPs at the late endosome membrane
R-HSA-168138: Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168898: Toll-Like Receptors Cascades

Summary
Symbol	PIK3C3
Name	phosphatidylinositol 3-kinase, catalytic subunit type 3
Aliases	Vps34; phosphoinositide-3-kinase, class 3; hVps34; PI3-kinase type 3; PI3K type 3; PtdIns-3-kinase type 3; p ......
Chromosomal Location	18q12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PIK3C3 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	PIK3C3
Name	phosphatidylinositol 3-kinase, catalytic subunit type 3
Aliases	Vps34; phosphoinositide-3-kinase, class 3; hVps34; PI3-kinase type 3; PI3K type 3; PtdIns-3-kinase type 3; p ......
Chromosomal Location	18q12.3
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 PIK3C3 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	Total # shRNA with >= 4-fold: 1	Resistant to T-cell proliferation
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	PIK3C3
Name	phosphatidylinositol 3-kinase, catalytic subunit type 3
Aliases	Vps34; phosphoinositide-3-kinase, class 3; hVps34; PI3-kinase type 3; PI3K type 3; PtdIns-3-kinase type 3; p ......
Chromosomal Location	18q12.3
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 PIK3C3 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	0.111	0.735
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.169	0.92
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.068	0.957
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.209	0.544
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.43	0.818
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.07	0.977
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.148	0.68
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.041	0.979
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.287	0.867
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.035	0.981
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	0.181	0.933
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.089	0.1

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PIK3C3 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	7.4	2.7	4.7	0.294
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	7.4	3.4	4	0.587
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	3.7	-1.1	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	7.1	-7.1	0.467
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	PIK3C3
Name	phosphatidylinositol 3-kinase, catalytic subunit type 3
Aliases	Vps34; phosphoinositide-3-kinase, class 3; hVps34; PI3-kinase type 3; PI3K type 3; PtdIns-3-kinase type 3; p ......
Chromosomal Location	18q12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PIK3C3. 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	PIK3C3
Name	phosphatidylinositol 3-kinase, catalytic subunit type 3
Aliases	Vps34; phosphoinositide-3-kinase, class 3; hVps34; PI3-kinase type 3; PI3K type 3; PtdIns-3-kinase type 3; p ......
Chromosomal Location	18q12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PIK3C3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PIK3C3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PIK3C3
Name	phosphatidylinositol 3-kinase, catalytic subunit type 3
Aliases	Vps34; phosphoinositide-3-kinase, class 3; hVps34; PI3-kinase type 3; PI3K type 3; PtdIns-3-kinase type 3; p ......
Chromosomal Location	18q12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PIK3C3. 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	PIK3C3
Name	phosphatidylinositol 3-kinase, catalytic subunit type 3
Aliases	Vps34; phosphoinositide-3-kinase, class 3; hVps34; PI3-kinase type 3; PI3K type 3; PtdIns-3-kinase type 3; p ......
Chromosomal Location	18q12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PIK3C3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PIK3C3
Name	phosphatidylinositol 3-kinase, catalytic subunit type 3
Aliases	Vps34; phosphoinositide-3-kinase, class 3; hVps34; PI3-kinase type 3; PI3K type 3; PtdIns-3-kinase type 3; p ......
Chromosomal Location	18q12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PIK3C3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PIK3C3
Name	phosphatidylinositol 3-kinase, catalytic subunit type 3
Aliases	Vps34; phosphoinositide-3-kinase, class 3; hVps34; PI3-kinase type 3; PI3K type 3; PtdIns-3-kinase type 3; p ......
Chromosomal Location	18q12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PIK3C3 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting PIK3C3.

ID	Name	Drug Type	Targets	#Targets
DB06836	N-(5-{4-Chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl}-4-methyl-1,3-thiazol-2-yl)acetamide	Small Molecule	PIK3C3, PIK3CG	2

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