Human Gene PITX2 (ENST00000644743.1) from GENCODE V43
  Description: Homo sapiens paired like homeodomain 2 (PITX2), transcript variant 3, mRNA. (from RefSeq NM_000325)
RefSeq Summary (NM_000325): This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. The encoded protein acts as a transcription factor and regulates procollagen lysyl hydroxylase gene expression. This protein plays a role in the terminal differentiation of somatotroph and lactotroph cell phenotypes, is involved in the development of the eye, tooth and abdominal organs, and acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin. Mutations in this gene are associated with Axenfeld-Rieger syndrome, iridogoniodysgenesis syndrome, and sporadic cases of Peters anomaly. A similar protein in other vertebrates is involved in the determination of left-right asymmetry during development. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008].
Gencode Transcript: ENST00000644743.1
Gencode Gene: ENSG00000164093.18
Transcript (Including UTRs)
   Position: hg38 chr4:110,617,423-110,623,077 Size: 5,655 Total Exon Count: 3 Strand: -
Coding Region
   Position: hg38 chr4:110,618,125-110,622,460 Size: 4,336 Coding Exon Count: 3 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-02-17 13:02:02

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr4:110,617,423-110,623,077)mRNA (may differ from genome)Protein (324 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSCGAPEnsemblEntrez GeneExonPrimerGencode
GeneCardsHGNCHPRDLynxMGImyGene2
neXtProtOMIMPubMedReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: PITX2_HUMAN
DESCRIPTION: RecName: Full=Pituitary homeobox 2; AltName: Full=ALL1-responsive protein ARP1; AltName: Full=Homeobox protein PITX2; AltName: Full=Paired-like homeodomain transcription factor 2; AltName: Full=RIEG bicoid-related homeobox transcription factor; AltName: Full=Solurshin;
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).
INTERACTION: Q12948:FOXC1; NbExp=6; IntAct=EBI-1175243, EBI-1175253;
SUBCELLULAR LOCATION: Nucleus.
PTM: Phosphorylation at Thr-90 impairs its association with the CCND1 mRNA-stabilizing complex thus shortening the half-life of CCND1 (By similarity).
DISEASE: Defects in PITX2 are the cause of Axenfeld-Rieger syndrome type 1 (RIEG1) [MIM:180500]; also known as Rieger syndrome type 1. RIEG1 is an autosomal dominant defect characterized by hypodontia (partial anodontia), anal stenosis, hypertelorism, mental deficiency, agenesis of the facial bones, with malformation of the anterior chamber of the eye.
DISEASE: Defects in PITX2 are the cause of iridogoniodysgenesis type 2 (IRID2) [MIM:137600]; also known as iridogoniodysgenesis syndrome 2 (IGDS2). It is an autosomal dominant inherited disease.
DISEASE: Defects in PITX2 are a cause of Peters anomaly (PAN) [MIM:604229]. It is a congenital defect of the anterior chamber of the eye.
DISEASE: Defects in PITX2 are associated with ring dermoid of cornea (RDC) [MIM:180550]. RDC is an autosomal dominantly inherited syndrome characterized by bilateral annular limbal dermoids with corneal and conjunctival extension.
SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily.
SIMILARITY: Contains 1 homeobox DNA-binding domain.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PITX2";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: PITX2
Diseases sorted by gene-association score: ring dermoid of cornea* (1679), axenfeld-rieger syndrome, type 1* (1329), anterior segment dysgenesis 4* (1247), axenfeld-rieger syndrome* (525), iris hypoplasia* (128), familial atrial fibrillation* (108), peters-plus syndrome* (65), aniridia (14), axenfeld-rieger syndrome, type 3 (12), cogan-reese syndrome (11), intestinal atresia (11), bardet-biedl syndrome 5 (9), autosomal dominant disease (8), anterior segment dysgenesis 1, multiple subtypes (8), fuchs' endothelial dystrophy (7), rieger syndrome, type 2 (7), early-onset glaucoma (7), juvenile glaucoma (7), hydrophthalmos (6), pigment dispersion syndrome (6), primary congenital glaucoma (6), tooth agenesis (5), glaucoma 3a, primary open angle, congenital, juvenile, or adult onset (5), transposition of the great arteries (5), iris disease (5), persistent hyperplastic primary vitreous (4), conotruncal heart malformations (4), visceral heterotaxy (4), heart disease (3), tetralogy of fallot (2), adamantinoma of long bones (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 9.84 RPKM in Bladder
Total median expression: 42.32 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -292.90617-0.475 Picture PostScript Text
3' UTR -165.20702-0.235 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR017970 - Homeobox_CS
IPR016233 - Homeobox_Pitx/unc30
IPR001356 - Homeodomain
IPR009057 - Homeodomain-like
IPR003654 - OAR_dom

Pfam Domains:
PF00046 - Homeobox domain
PF03826 - OAR domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2L7F - NMR MuPIT 2L7M - NMR MuPIT 2LKX - NMR MuPIT


ModBase Predicted Comparative 3D Structure on Q99697
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000976 transcription regulatory region sequence-specific DNA binding
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0001078 transcriptional repressor 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:0001105 RNA polymerase II transcription coactivator activity
GO:0001191 transcriptional repressor activity, RNA polymerase II transcription factor binding
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0031490 chromatin DNA binding
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0043021 ribonucleoprotein complex binding
GO:0043565 sequence-specific DNA binding
GO:0051219 phosphoprotein binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001569 branching involved in blood vessel morphogenesis
GO:0001570 vasculogenesis
GO:0001701 in utero embryonic development
GO:0001764 neuron migration
GO:0002074 extraocular skeletal muscle development
GO:0003171 atrioventricular valve development
GO:0003253 cardiac neural crest cell migration involved in outflow tract morphogenesis
GO:0003350 pulmonary myocardium development
GO:0006355 regulation of transcription, DNA-templated
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006366 transcription from RNA polymerase II promoter
GO:0007275 multicellular organism development
GO:0007368 determination of left/right symmetry
GO:0007420 brain development
GO:0007507 heart development
GO:0007519 skeletal muscle tissue development
GO:0007520 myoblast fusion
GO:0008584 male gonad development
GO:0008585 female gonad development
GO:0009653 anatomical structure morphogenesis
GO:0009725 response to hormone
GO:0009887 animal organ morphogenesis
GO:0016055 Wnt signaling pathway
GO:0021763 subthalamic nucleus development
GO:0021855 hypothalamus cell migration
GO:0021983 pituitary gland development
GO:0030182 neuron differentiation
GO:0030324 lung development
GO:0030334 regulation of cell migration
GO:0031076 embryonic camera-type eye development
GO:0033189 response to vitamin A
GO:0035116 embryonic hindlimb morphogenesis
GO:0035315 hair cell differentiation
GO:0035886 vascular smooth muscle cell differentiation
GO:0035993 deltoid tuberosity development
GO:0042127 regulation of cell proliferation
GO:0042475 odontogenesis of dentin-containing tooth
GO:0042476 odontogenesis
GO:0043010 camera-type eye development
GO:0043388 positive regulation of DNA binding
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048536 spleen development
GO:0048557 embryonic digestive tract morphogenesis
GO:0048738 cardiac muscle tissue development
GO:0055007 cardiac muscle cell differentiation
GO:0055009 atrial cardiac muscle tissue morphogenesis
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:0060412 ventricular septum morphogenesis
GO:0060460 left lung morphogenesis
GO:0060577 pulmonary vein morphogenesis
GO:0060578 superior vena cava morphogenesis
GO:0061031 endodermal digestive tract morphogenesis
GO:0061072 iris morphogenesis
GO:0061325 cell proliferation involved in outflow tract morphogenesis
GO:0070986 left/right axis specification
GO:2000288 positive regulation of myoblast proliferation

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005667 transcription factor complex
GO:0005737 cytoplasm


-  Descriptions from all associated GenBank mRNAs
  LF206336 - JP 2014500723-A/13839: Polycomb-Associated Non-Coding RNAs.
MA441913 - JP 2018138019-A/13839: Polycomb-Associated Non-Coding RNAs.
BC106010 - Homo sapiens paired-like homeodomain 2, mRNA (cDNA clone MGC:111022 IMAGE:3914727), complete cds.
AF048720 - Homo sapiens ALL1 responsive protein ARP1a (ARP1) mRNA, complete cds.
AF048721 - Homo sapiens ALL1 responsive protein ARP1b (ARP1) mRNA, complete cds.
U69961 - Homo sapiens solurshin (RGS) mRNA, complete cds.
AK127829 - Homo sapiens cDNA FLJ45932 fis, clone PLACE7002303, highly similar to Pituitary homeobox 2.
AK291591 - Homo sapiens cDNA FLJ77320 complete cds, highly similar to Homo sapiens paired-like homeodomain transcription factor 2 (PITX2), transcript variant 1, mRNA.
AF048722 - Homo sapiens ALL1 responsive protein ARP1c (ARP1) mRNA, complete cds.
BC013998 - Homo sapiens paired-like homeodomain 2, mRNA (cDNA clone MGC:20144 IMAGE:3937807), complete cds.
JD093947 - Sequence 74971 from Patent EP1572962.
JD363335 - Sequence 344359 from Patent EP1572962.
JD269367 - Sequence 250391 from Patent EP1572962.
JD310685 - Sequence 291709 from Patent EP1572962.
JD062498 - Sequence 43522 from Patent EP1572962.
JD058560 - Sequence 39584 from Patent EP1572962.
LF353290 - JP 2014500723-A/160793: Polycomb-Associated Non-Coding RNAs.
MA588867 - JP 2018138019-A/160793: Polycomb-Associated Non-Coding RNAs.
JD241540 - Sequence 222564 from Patent EP1572962.
DQ896741 - Synthetic construct Homo sapiens clone IMAGE:100011201; FLH199420.01L; RZPDo839F1081D paired-like homeodomain transcription factor 2 (PITX2) gene, encodes complete protein.
AK313987 - Homo sapiens cDNA, FLJ94639, Homo sapiens paired-like homeodomain transcription factor 2(PITX2), transcript variant 3, mRNA.
KJ891816 - Synthetic construct Homo sapiens clone ccsbBroadEn_01210 PITX2 gene, encodes complete protein.
KR710426 - Synthetic construct Homo sapiens clone CCSBHm_00012480 PITX2 (PITX2) mRNA, encodes complete protein.
KR710427 - Synthetic construct Homo sapiens clone CCSBHm_00012484 PITX2 (PITX2) mRNA, encodes complete protein.
KR710428 - Synthetic construct Homo sapiens clone CCSBHm_00012488 PITX2 (PITX2) mRNA, encodes complete protein.
KR710429 - Synthetic construct Homo sapiens clone CCSBHm_00012499 PITX2 (PITX2) mRNA, encodes complete protein.
DQ893426 - Synthetic construct clone IMAGE:100006056; FLH199514.01X; RZPDo839F1082D paired-like homeodomain transcription factor 2 (PITX2) gene, encodes complete protein.
AB528392 - Synthetic construct DNA, clone: pF1KB7984, Homo sapiens PITX2 gene for paired-like homeodomain 2, without stop codon, in Flexi system.
CU680732 - Synthetic construct Homo sapiens gateway clone IMAGE:100018932 5' read PITX2 mRNA.
BC007987 - Homo sapiens protein phosphatase 1, regulatory (inhibitor) subunit 15A, mRNA (cDNA clone IMAGE:3028779), **** WARNING: chimeric clone ****.
LF211934 - JP 2014500723-A/19437: Polycomb-Associated Non-Coding RNAs.
MA447511 - JP 2018138019-A/19437: Polycomb-Associated Non-Coding RNAs.
JD555273 - Sequence 536297 from Patent EP1572962.
JD540718 - Sequence 521742 from Patent EP1572962.
JD219860 - Sequence 200884 from Patent EP1572962.
JD343265 - Sequence 324289 from Patent EP1572962.
JD092634 - Sequence 73658 from Patent EP1572962.
JD194528 - Sequence 175552 from Patent EP1572962.
JD406478 - Sequence 387502 from Patent EP1572962.
JD396586 - Sequence 377610 from Patent EP1572962.
JD545892 - Sequence 526916 from Patent EP1572962.
JD310535 - Sequence 291559 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04350 - TGF-beta signaling pathway

BioCarta from NCI Cancer Genome Anatomy Project
h_pitx2Pathway - Multi-step Regulation of Transcription by Pitx2

Reactome (by CSHL, EBI, and GO)

Protein Q99697 (Reactome details) participates in the following event(s):

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
R-HSA-212436 Generic Transcription Pathway
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: ARP1, B2RA02, B3KXS0, NM_000325, O60578, O60579, O60580, PITX2_HUMAN, Q3KQX9, Q99697, Q9BY17, RGS, RIEG, RIEG1, uc003iac.1, uc003iac.2, uc003iac.3, uc003iac.4, uc003iac.5
UCSC ID: ENST00000644743.1
RefSeq Accession: NM_000325
Protein: Q99697 (aka PITX2_HUMAN)
CCDS: CCDS3694.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.