TISIDB

Summary
Symbol	ITIH4
Name	inter-alpha-trypsin inhibitor heavy chain family, member 4
Aliases	IHRP; H4P; plasma Kallikrein-sensitive glycoprotein; ITIHL1; inter-alpha (globulin) inhibitor H4 (plasma Kal ......
Chromosomal Location	3p21.1
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	Secreted.
Domain	PF06668 Inter-alpha-trypsin inhibitor heavy chain C-terminus PF08487 Vault protein inter-alpha-trypsin domain PF00092 von Willebrand factor type A domain
Function	Type II acute-phase protein (APP) involved in inflammatory responses to trauma. May also play a role in liver development or regeneration.

> Gene Ontology [ TOP ]
Biological Process	GO:0002526 acute inflammatory response GO:0002576 platelet degranulation GO:0006022 aminoglycan metabolic process GO:0006887 exocytosis GO:0006953 acute-phase response GO:0010466 negative regulation of peptidase activity GO:0010951 negative regulation of endopeptidase activity GO:0030203 glycosaminoglycan metabolic process GO:0030212 hyaluronan metabolic process GO:0045055 regulated exocytosis GO:0045861 negative regulation of proteolysis GO:0051346 negative regulation of hydrolase activity GO:0052547 regulation of peptidase activity GO:0052548 regulation of endopeptidase activity GO:1903510 mucopolysaccharide metabolic process
Molecular Function	GO:0004857 enzyme inhibitor activity GO:0004866 endopeptidase inhibitor activity GO:0004867 serine-type endopeptidase inhibitor activity GO:0030414 peptidase inhibitor activity GO:0061134 peptidase regulator activity GO:0061135 endopeptidase regulator activity
Cellular Component	GO:0030141 secretory granule GO:0031089 platelet dense granule lumen GO:0031983 vesicle lumen GO:0034774 secretory granule lumen GO:0042827 platelet dense granule GO:0060205 cytoplasmic membrane-bounded vesicle lumen GO:0072562 blood microparticle GO:0099503 secretory vesicle

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-109582: Hemostasis R-HSA-76002: Platelet activation, signaling and aggregation R-HSA-114608: Platelet degranulation R-HSA-76005: Response to elevated platelet cytosolic Ca2+

Summary
Symbol	ITIH4
Name	inter-alpha-trypsin inhibitor heavy chain family, member 4
Aliases	IHRP; H4P; plasma Kallikrein-sensitive glycoprotein; ITIHL1; inter-alpha (globulin) inhibitor H4 (plasma Kal ......
Chromosomal Location	3p21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ITIH4 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	ITIH4
Name	inter-alpha-trypsin inhibitor heavy chain family, member 4
Aliases	IHRP; H4P; plasma Kallikrein-sensitive glycoprotein; ITIHL1; inter-alpha (globulin) inhibitor H4 (plasma Kal ......
Chromosomal Location	3p21.1
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 ITIH4 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	ITIH4
Name	inter-alpha-trypsin inhibitor heavy chain family, member 4
Aliases	IHRP; H4P; plasma Kallikrein-sensitive glycoprotein; ITIHL1; inter-alpha (globulin) inhibitor H4 (plasma Kal ......
Chromosomal Location	3p21.1
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 ITIH4 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	0.897	0.225
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.31	0.803
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	1.802	0.0584
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.401	0.411
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.484	0.745
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.527	0.46
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.031	0.964
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.715	0.472
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.987	0.416
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.091	0.96
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	2.189	0.322
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.334	0.0602

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ITIH4 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	11.1	0	11.1	0.0181
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	11.1	0	11.1	0.0286
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	11.1	6.2	4.9	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	11.1	8.9	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	0	0	0	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	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	ITIH4
Name	inter-alpha-trypsin inhibitor heavy chain family, member 4
Aliases	IHRP; H4P; plasma Kallikrein-sensitive glycoprotein; ITIHL1; inter-alpha (globulin) inhibitor H4 (plasma Kal ......
Chromosomal Location	3p21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ITIH4. 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	ITIH4
Name	inter-alpha-trypsin inhibitor heavy chain family, member 4
Aliases	IHRP; H4P; plasma Kallikrein-sensitive glycoprotein; ITIHL1; inter-alpha (globulin) inhibitor H4 (plasma Kal ......
Chromosomal Location	3p21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ITIH4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ITIH4. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ITIH4
Name	inter-alpha-trypsin inhibitor heavy chain family, member 4
Aliases	IHRP; H4P; plasma Kallikrein-sensitive glycoprotein; ITIHL1; inter-alpha (globulin) inhibitor H4 (plasma Kal ......
Chromosomal Location	3p21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ITIH4. 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	ITIH4
Name	inter-alpha-trypsin inhibitor heavy chain family, member 4
Aliases	IHRP; H4P; plasma Kallikrein-sensitive glycoprotein; ITIHL1; inter-alpha (globulin) inhibitor H4 (plasma Kal ......
Chromosomal Location	3p21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ITIH4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ITIH4
Name	inter-alpha-trypsin inhibitor heavy chain family, member 4
Aliases	IHRP; H4P; plasma Kallikrein-sensitive glycoprotein; ITIHL1; inter-alpha (globulin) inhibitor H4 (plasma Kal ......
Chromosomal Location	3p21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ITIH4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ITIH4
Name	inter-alpha-trypsin inhibitor heavy chain family, member 4
Aliases	IHRP; H4P; plasma Kallikrein-sensitive glycoprotein; ITIHL1; inter-alpha (globulin) inhibitor H4 (plasma Kal ......
Chromosomal Location	3p21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ITIH4 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting ITIH4.

ID	Name	Drug Type	Targets	#Targets
DB01593	Zinc	Small Molecule	A1BG, A2M, AGT, AHSG, ALDOA, APCS, APLP1, APLP2, APOA1, APOA2, APO ......	119

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