TISIDB

Summary
Symbol	IKZF1
Name	IKAROS family zinc finger 1 (Ikaros)
Aliases	hIk-1; LyF-1; Hs.54452; IKAROS; PPP1R92; protein phosphatase 1, regulatory subunit 92; ZNFN1A1; zinc finger ......
Chromosomal Location	7p12.2
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	Nucleus Note=In resting lymphocytes, distributed diffusely throughout the nucleus. Localizes to pericentromeric heterochromatin in proliferating cells. This localization requires DNA binding which is regulated by phosphorylation / dephosphorylation events. ; SUBCELLULAR LOCATION: Isoform Ik2: Nucleus. Note=In resting lymphocytes, distributed diffusely throughout the nucleus. Localizes to pericentromeric heterochromatin in proliferating cells. This localization requires DNA binding which is regulated by phosphorylation / dephosphorylation events (By similarity). ; SUBCELLULAR LOCATION: Isoform Ik6: Cytoplasm
Domain	-
Function	Transcription regulator of hematopoietic cell differentiation (PubMed:17934067). Binds gamma-satellite DNA (PubMed:17135265, PubMed:19141594). Plays a role in the development of lymphocytes, B- and T-cells. Binds and activates the enhancer (delta-A element) of the CD3-delta gene. Repressor of the TDT (fikzfterminal deoxynucleotidyltransferase) gene during thymocyte differentiation. Regulates transcription through association with both HDAC-dependent and HDAC-independent complexes. Targets the 2 chromatin-remodeling complexes, NuRD and BAF (SWI/SNF), in a single complex (PYR complex), to the beta-globin locus in adult erythrocytes. Increases normal apoptosis in adult erythroid cells. Confers early temporal competence to retinal progenitor cells (RPCs) (By similarity). Function is isoform-specific and is modulated by dominant-negative inactive isoforms (PubMed:17135265, PubMed:17934067).

> Gene Ontology [ TOP ]
Biological Process	GO:0002262 myeloid cell homeostasis GO:0002521 leukocyte differentiation GO:0007498 mesoderm development GO:0030098 lymphocyte differentiation GO:0030099 myeloid cell differentiation GO:0030218 erythrocyte differentiation GO:0034101 erythrocyte homeostasis GO:0048872 homeostasis of number of cells
Molecular Function	-
Cellular Component	GO:0000775 chromosome, centromeric region GO:0000785 chromatin GO:0000790 nuclear chromatin GO:0000792 heterochromatin GO:0005720 nuclear heterochromatin GO:0005721 pericentric heterochromatin GO:0031618 nuclear pericentric heterochromatin GO:0044454 nuclear chromosome part GO:0098687 chromosomal region

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

Summary
Symbol	IKZF1
Name	IKAROS family zinc finger 1 (Ikaros)
Aliases	hIk-1; LyF-1; Hs.54452; IKAROS; PPP1R92; protein phosphatase 1, regulatory subunit 92; ZNFN1A1; zinc finger ......
Chromosomal Location	7p12.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between IKZF1 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 IKZF1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
24778448	Melanoma	Inhibit immunity (T cell function)	Naive murine CD8 T cells haplo-insufficient for Ikzf1 failed to upregulate Ikaros, produced autocrine IL-2, and differentiated in an IL-2-dependent manner into IFN-γ-producing CTLs in response to TCR/CD28 stimulation alone. Furthermore, Ikzf1 haplo-insufficient CD8(+) T cells were more effective at controlling Listeria infection and B16 melanoma growth in vivo, and they could provide help to neighboring, non-IL-2-producing cells to differentiate into IFN-γ-producing effectors.

Summary
Symbol	IKZF1
Name	IKAROS family zinc finger 1 (Ikaros)
Aliases	hIk-1; LyF-1; Hs.54452; IKAROS; PPP1R92; protein phosphatase 1, regulatory subunit 92; ZNFN1A1; zinc finger ......
Chromosomal Location	7p12.2
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 IKZF1 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	IKZF1
Name	IKAROS family zinc finger 1 (Ikaros)
Aliases	hIk-1; LyF-1; Hs.54452; IKAROS; PPP1R92; protein phosphatase 1, regulatory subunit 92; ZNFN1A1; zinc finger ......
Chromosomal Location	7p12.2
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 IKZF1 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	-0.033	0.944
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.618	0.582
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.508	0.563
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.253	0.595
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.418	0.656
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.11	0.372
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.659	0.207
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.042	0.442
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.241	0.873
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.717	0.0821
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	1.512	0.329
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.233	0.262

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of IKZF1 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	2.7	-2.7	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	3.4	-3.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	5.9	3.6	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	16.7	-16.7	0.429
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	15.4	0	15.4	0.482
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	5.3	0	5.3	0.507
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	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	IKZF1
Name	IKAROS family zinc finger 1 (Ikaros)
Aliases	hIk-1; LyF-1; Hs.54452; IKAROS; PPP1R92; protein phosphatase 1, regulatory subunit 92; ZNFN1A1; zinc finger ......
Chromosomal Location	7p12.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of IKZF1. 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	IKZF1
Name	IKAROS family zinc finger 1 (Ikaros)
Aliases	hIk-1; LyF-1; Hs.54452; IKAROS; PPP1R92; protein phosphatase 1, regulatory subunit 92; ZNFN1A1; zinc finger ......
Chromosomal Location	7p12.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of IKZF1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by IKZF1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	IKZF1
Name	IKAROS family zinc finger 1 (Ikaros)
Aliases	hIk-1; LyF-1; Hs.54452; IKAROS; PPP1R92; protein phosphatase 1, regulatory subunit 92; ZNFN1A1; zinc finger ......
Chromosomal Location	7p12.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of IKZF1. 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	IKZF1
Name	IKAROS family zinc finger 1 (Ikaros)
Aliases	hIk-1; LyF-1; Hs.54452; IKAROS; PPP1R92; protein phosphatase 1, regulatory subunit 92; ZNFN1A1; zinc finger ......
Chromosomal Location	7p12.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of IKZF1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	IKZF1
Name	IKAROS family zinc finger 1 (Ikaros)
Aliases	hIk-1; LyF-1; Hs.54452; IKAROS; PPP1R92; protein phosphatase 1, regulatory subunit 92; ZNFN1A1; zinc finger ......
Chromosomal Location	7p12.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between IKZF1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	IKZF1
Name	IKAROS family zinc finger 1 (Ikaros)
Aliases	hIk-1; LyF-1; Hs.54452; IKAROS; PPP1R92; protein phosphatase 1, regulatory subunit 92; ZNFN1A1; zinc finger ......
Chromosomal Location	7p12.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting IKZF1 collected from DrugBank database.

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

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