TISIDB

Summary
Symbol	PITX2
Name	paired-like homeodomain 2
Aliases	IGDS; Brx1; Otlx2; IRID2; IHG2; RIEG; RIEG1; RGS; paired-like homeodomain transcription factor 2; IDG2; IGDS ......
Chromosomal Location	4q25
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.
Domain	PF00046 Homeobox domain PF03826 OAR domain
Function	Controls cell proliferation in a tissue-specific manner and is involved in morphogenesis. During embryonic development, exerts a role in the expansion of muscle progenitors. May play a role in the proper localization of asymmetric organs such as the heart and stomach. Isoform PTX2C is involved in left-right asymmetry the developing embryo (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0000768 syncytium formation by plasma membrane fusion GO:0001501 skeletal system development GO:0001525 angiogenesis GO:0001569 patterning of blood vessels GO:0001570 vasculogenesis GO:0001654 eye development GO:0001667 ameboidal-type cell migration GO:0001701 in utero embryonic development GO:0001755 neural crest cell migration GO:0001763 morphogenesis of a branching structure GO:0001764 neuron migration GO:0002074 extraocular skeletal muscle development GO:0003002 regionalization GO:0003007 heart morphogenesis GO:0003151 outflow tract morphogenesis GO:0003170 heart valve development GO:0003171 atrioventricular valve development GO:0003205 cardiac chamber development GO:0003206 cardiac chamber morphogenesis GO:0003209 cardiac atrium morphogenesis GO:0003228 atrial cardiac muscle tissue development GO:0003230 cardiac atrium development GO:0003231 cardiac ventricle development GO:0003253 cardiac neural crest cell migration involved in outflow tract morphogenesis GO:0003279 cardiac septum development GO:0003281 ventricular septum development GO:0003350 pulmonary myocardium development GO:0006949 syncytium formation GO:0007368 determination of left/right symmetry GO:0007389 pattern specification process GO:0007423 sensory organ development GO:0007507 heart development GO:0007517 muscle organ development GO:0007519 skeletal muscle tissue development GO:0007520 myoblast fusion GO:0007548 sex differentiation GO:0007584 response to nutrient GO:0008406 gonad development GO:0008544 epidermis development GO:0008584 male gonad development GO:0008585 female gonad development GO:0009798 axis specification GO:0009799 specification of symmetry GO:0009855 determination of bilateral symmetry GO:0009913 epidermal cell differentiation GO:0009991 response to extracellular stimulus GO:0014031 mesenchymal cell development GO:0014032 neural crest cell development GO:0014033 neural crest cell differentiation GO:0014706 striated muscle tissue development GO:0014902 myotube differentiation GO:0016055 Wnt signaling pathway GO:0021536 diencephalon development GO:0021539 subthalamus development GO:0021761 limbic system development GO:0021763 subthalamic nucleus development GO:0021854 hypothalamus development GO:0021855 hypothalamus cell migration GO:0021983 pituitary gland development GO:0021984 adenohypophysis development GO:0030323 respiratory tube development GO:0030324 lung development GO:0030326 embryonic limb morphogenesis GO:0030900 forebrain development GO:0031076 embryonic camera-type eye development GO:0031667 response to nutrient levels GO:0033189 response to vitamin A GO:0033273 response to vitamin GO:0035051 cardiocyte differentiation GO:0035107 appendage morphogenesis GO:0035108 limb morphogenesis GO:0035113 embryonic appendage morphogenesis GO:0035116 embryonic hindlimb morphogenesis GO:0035137 hindlimb morphogenesis GO:0035239 tube morphogenesis GO:0035270 endocrine system development GO:0035315 hair cell differentiation GO:0035886 vascular smooth muscle cell differentiation GO:0035993 deltoid tuberosity development GO:0042475 odontogenesis of dentin-containing tooth GO:0042476 odontogenesis GO:0042692 muscle cell differentiation GO:0043010 camera-type eye development GO:0043388 positive regulation of DNA binding GO:0045137 development of primary sexual characteristics GO:0046545 development of primary female sexual characteristics GO:0046546 development of primary male sexual characteristics GO:0046660 female sex differentiation GO:0046661 male sex differentiation GO:0048514 blood vessel morphogenesis GO:0048536 spleen development GO:0048546 digestive tract morphogenesis GO:0048557 embryonic digestive tract morphogenesis GO:0048562 embryonic organ morphogenesis GO:0048565 digestive tract development GO:0048566 embryonic digestive tract development GO:0048568 embryonic organ development GO:0048592 eye morphogenesis GO:0048593 camera-type eye morphogenesis GO:0048608 reproductive structure development GO:0048644 muscle organ morphogenesis GO:0048732 gland development GO:0048736 appendage development GO:0048738 cardiac muscle tissue development GO:0048754 branching morphogenesis of an epithelial tube GO:0048762 mesenchymal cell differentiation GO:0048845 venous blood vessel morphogenesis GO:0048857 neural nucleus development GO:0048863 stem cell differentiation GO:0048864 stem cell development GO:0051098 regulation of binding GO:0051099 positive regulation of binding GO:0051101 regulation of DNA binding GO:0051145 smooth muscle cell differentiation GO:0051146 striated muscle cell differentiation GO:0051450 myoblast proliferation GO:0055001 muscle cell development GO:0055002 striated muscle cell development GO:0055006 cardiac cell development GO:0055007 cardiac muscle cell differentiation GO:0055008 cardiac muscle tissue morphogenesis GO:0055009 atrial cardiac muscle tissue morphogenesis GO:0055012 ventricular cardiac muscle cell differentiation GO:0055013 cardiac muscle cell development GO:0055015 ventricular cardiac muscle cell development GO:0055123 digestive system development GO:0060126 somatotropin secreting cell differentiation GO:0060127 prolactin secreting cell differentiation GO:0060173 limb development GO:0060348 bone development GO:0060411 cardiac septum morphogenesis GO:0060412 ventricular septum morphogenesis GO:0060415 muscle tissue morphogenesis GO:0060425 lung morphogenesis GO:0060459 left lung development GO:0060460 left lung morphogenesis GO:0060485 mesenchyme development GO:0060537 muscle tissue development GO:0060538 skeletal muscle organ development GO:0060541 respiratory system development GO:0060562 epithelial tube morphogenesis GO:0060577 pulmonary vein morphogenesis GO:0060578 superior vena cava morphogenesis GO:0060841 venous blood vessel development GO:0060972 left/right pattern formation GO:0060973 cell migration involved in heart development GO:0061031 endodermal digestive tract morphogenesis GO:0061072 iris morphogenesis GO:0061138 morphogenesis of a branching epithelium GO:0061307 cardiac neural crest cell differentiation involved in heart development GO:0061308 cardiac neural crest cell development involved in heart development GO:0061309 cardiac neural crest cell development involved in outflow tract morphogenesis GO:0061323 cell proliferation involved in heart morphogenesis GO:0061325 cell proliferation involved in outflow tract morphogenesis GO:0061458 reproductive system development GO:0070986 left/right axis specification GO:0090596 sensory organ morphogenesis GO:0198738 cell-cell signaling by wnt GO:2000288 positive regulation of myoblast proliferation GO:2000291 regulation of myoblast proliferation
Molecular Function	GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0000987 core promoter proximal region sequence-specific DNA binding GO:0001076 transcription factor activity, RNA polymerase II transcription factor binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001085 RNA polymerase II transcription factor binding GO:0001102 RNA polymerase II activating transcription factor binding GO:0001104 RNA polymerase II transcription cofactor activity GO:0001105 RNA polymerase II transcription coactivator activity GO:0001159 core promoter proximal region DNA binding GO:0001190 transcriptional activator activity, RNA polymerase II transcription factor binding GO:0001191 transcriptional repressor activity, RNA polymerase II transcription factor binding GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0003682 chromatin binding GO:0003713 transcription coactivator activity GO:0008134 transcription factor binding GO:0031490 chromatin DNA binding GO:0033613 activating transcription factor binding GO:0043566 structure-specific DNA binding GO:0098811 transcriptional repressor activity, RNA polymerase II activating transcription factor binding
Cellular Component	GO:0005667 transcription factor complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04350 TGF-beta signaling pathway
Reactome	R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-8866906: TFAP2 (AP-2) family regulates transcription of other transcription factors R-HSA-8864260: Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors

Summary
Symbol	PITX2
Name	paired-like homeodomain 2
Aliases	IGDS; Brx1; Otlx2; IRID2; IHG2; RIEG; RIEG1; RGS; paired-like homeodomain transcription factor 2; IDG2; IGDS ......
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PITX2 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	PITX2
Name	paired-like homeodomain 2
Aliases	IGDS; Brx1; Otlx2; IRID2; IHG2; RIEG; RIEG1; RGS; paired-like homeodomain transcription factor 2; IDG2; IGDS ......
Chromosomal Location	4q25
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

[ TOP ]

Statistical results of PITX2 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	logFC: -2.56; FDR: 0.04180	Resistant to T cell-mediated killing
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	PITX2
Name	paired-like homeodomain 2
Aliases	IGDS; Brx1; Otlx2; IRID2; IHG2; RIEG; RIEG1; RGS; paired-like homeodomain transcription factor 2; IDG2; IGDS ......
Chromosomal Location	4q25
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

[ TOP ]

Points in the above scatter plot represent the expression difference of PITX2 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	0.05	0.906
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.621	0.369
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.528	0.417
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.797	0.115
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.964	0.499
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.582	0.723
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.717	0.461
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.599	0.244
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.23	0.875
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.224	0.807
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	-1.328	0.277
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.526	0.127

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of PITX2 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	3.7	1.4	2.3	0.469
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	3.7	1.7	2	0.532
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	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	1
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	11.1	-11.1	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	PITX2
Name	paired-like homeodomain 2
Aliases	IGDS; Brx1; Otlx2; IRID2; IHG2; RIEG; RIEG1; RGS; paired-like homeodomain transcription factor 2; IDG2; IGDS ......
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PITX2. 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	PITX2
Name	paired-like homeodomain 2
Aliases	IGDS; Brx1; Otlx2; IRID2; IHG2; RIEG; RIEG1; RGS; paired-like homeodomain transcription factor 2; IDG2; IGDS ......
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PITX2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PITX2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PITX2
Name	paired-like homeodomain 2
Aliases	IGDS; Brx1; Otlx2; IRID2; IHG2; RIEG; RIEG1; RGS; paired-like homeodomain transcription factor 2; IDG2; IGDS ......
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PITX2. 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	PITX2
Name	paired-like homeodomain 2
Aliases	IGDS; Brx1; Otlx2; IRID2; IHG2; RIEG; RIEG1; RGS; paired-like homeodomain transcription factor 2; IDG2; IGDS ......
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PITX2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PITX2
Name	paired-like homeodomain 2
Aliases	IGDS; Brx1; Otlx2; IRID2; IHG2; RIEG; RIEG1; RGS; paired-like homeodomain transcription factor 2; IDG2; IGDS ......
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PITX2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PITX2
Name	paired-like homeodomain 2
Aliases	IGDS; Brx1; Otlx2; IRID2; IHG2; RIEG; RIEG1; RGS; paired-like homeodomain transcription factor 2; IDG2; IGDS ......
Chromosomal Location	4q25
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PITX2 collected from DrugBank database.

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

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