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PITX2 paired-like homeodomain 2 [ Homo sapiens (human) ]

Gene ID: 5308, updated on 15-Sep-2014
Official Symbol
PITX2provided by HGNC
Official Full Name
paired-like homeodomain 2provided by HGNC
Primary source
HGNC:HGNC:9005
See related
Ensembl:ENSG00000164093; HPRD:03328; MIM:601542; Vega:OTTHUMG00000132837
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
RS; RGS; ARP1; Brx1; IDG2; IGDS; IHG2; PTX2; RIEG; IGDS2; IRID2; Otlx2; RIEG1
Summary
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]
See PITX2 in Epigenomics, MapViewer
Location:
4q25
Exon count:
9
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 4 NC_000004.12 (110617423..110642123, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (111538579..111563279, complement)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene zinc finger protein 969, pseudogene Neighboring gene glutamyl aminopeptidase (aminopeptidase A) Neighboring gene microRNA 297 Neighboring gene lysophospholipase I pseudogene 2

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Anophthalmia/Microphthalmia Compare labs
Axenfeld-Rieger syndrome type 1
MedGen: CN029264 OMIM: 180500 GeneReviews: Not available
Compare labs
Irido-corneo-trabecular dysgenesis
MedGen: C0344559 OMIM: 604229 GeneReviews: Not available
Compare labs
Iridogoniodysgenesis, dominant type
MedGen: C1842031 OMIM: 137600 GeneReviews: Not available
Compare labs
Ring dermoid of cornea
MedGen: C1867155 OMIM: 180550 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated (2012-07-06)

ISCA Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated (2012-07-06)

ISCA Genome Curation PagePubMed

NHGRI GWAS Catalog

Description
Common variants in KCNN3 are associated with lone atrial fibrillation.
NHGRI GWA Catalog
Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies.
NHGRI GWA Catalog
Meta-analysis identifies six new susceptibility loci for atrial fibrillation.
NHGRI GWA Catalog
Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.
NHGRI GWA Catalog
Variants conferring risk of atrial fibrillation on chromosome 4q25.
NHGRI GWA Catalog
Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry.
NHGRI GWA Catalog
  • Heart Development, organism-specific biosystem (from WikiPathways)
    Heart Development, organism-specific biosystemThis pathway has been largely adapted from an article by Deepak Srivastava, Cell. 2006 Sep 22;126(6):1037-48. In this pathway are known transcription factors, miRNAs and regulatory proteins that impa...
  • Integrated Pancreatic Cancer Pathway, organism-specific biosystem (from WikiPathways)
    Integrated Pancreatic Cancer Pathway, organism-specific biosystemAn integrated pathway model which displays the protein-protein interactions (PPIs) among the relevant proteins for pancreatic cancer. This pathway is a collection of different mechanistic protein pat...
  • Regulation of Wnt-mediated beta catenin signaling and target gene transcription, organism-specific biosystem (from Pathway Interaction Database)
    Regulation of Wnt-mediated beta catenin signaling and target gene transcription, organism-specific biosystem
    Regulation of Wnt-mediated beta catenin signaling and target gene transcription
  • TGF-beta signaling pathway, organism-specific biosystem (from KEGG)
    TGF-beta signaling pathway, organism-specific biosystemThe transforming growth factor-beta (TGF-beta) family members, which include TGF-betas, activins and bone morphogenetic proteins (BMPs), are structurally related secreted cytokines found in species r...
  • TGF-beta signaling pathway, conserved biosystem (from KEGG)
    TGF-beta signaling pathway, conserved biosystemThe transforming growth factor-beta (TGF-beta) family members, which include TGF-betas, activins and bone morphogenetic proteins (BMPs), are structurally related secreted cytokines found in species r...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • MGC20144, MGC111022

Gene Ontology Provided by GOA

Function Evidence Code Pubs
RNA polymerase II activating transcription factor binding IPI
Inferred from Physical Interaction
more info
PubMed 
RNA polymerase II core promoter proximal region sequence-specific DNA binding IEA
Inferred from Electronic Annotation
more info
 
RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription IDA
Inferred from Direct Assay
more info
PubMed 
RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription IEA
Inferred from Electronic Annotation
more info
 
RNA polymerase II transcription coactivator activity IDA
Inferred from Direct Assay
more info
PubMed 
RNA polymerase II transcription factor binding IPI
Inferred from Physical Interaction
more info
PubMed 
RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription IDA
Inferred from Direct Assay
more info
PubMed 
chromatin DNA binding IEA
Inferred from Electronic Annotation
more info
 
phosphoprotein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IPI
Inferred from Physical Interaction
more info
PubMed 
ribonucleoprotein complex binding IC
Inferred by Curator
more info
PubMed 
sequence-specific DNA binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
transcription factor binding IPI
Inferred from Physical Interaction
more info
PubMed 
transcription regulatory region sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
Wnt signaling pathway IEA
Inferred from Electronic Annotation
more info
 
atrial cardiac muscle tissue morphogenesis IEA
Inferred from Electronic Annotation
more info
 
atrioventricular valve development IEA
Inferred from Electronic Annotation
more info
 
camera-type eye development IMP
Inferred from Mutant Phenotype
more info
PubMed 
cardiac neural crest cell migration involved in outflow tract morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
cell proliferation involved in outflow tract morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
deltoid tuberosity development IMP
Inferred from Mutant Phenotype
more info
PubMed 
determination of left/right symmetry ISS
Inferred from Sequence or Structural Similarity
more info
 
embryonic camera-type eye development IEA
Inferred from Electronic Annotation
more info
 
embryonic digestive tract morphogenesis IEA
Inferred from Electronic Annotation
more info
 
embryonic hindlimb morphogenesis IEA
Inferred from Electronic Annotation
more info
 
endodermal digestive tract morphogenesis IEA
Inferred from Electronic Annotation
more info
 
extraocular skeletal muscle development IEA
Inferred from Electronic Annotation
more info
 
female gonad development IEA
Inferred from Electronic Annotation
more info
 
hair cell differentiation IC
Inferred by Curator
more info
PubMed 
hypothalamus cell migration IEA
Inferred from Electronic Annotation
more info
 
in utero embryonic development IEA
Inferred from Electronic Annotation
more info
 
iris morphogenesis IMP
Inferred from Mutant Phenotype
more info
PubMed 
left lung morphogenesis IEA
Inferred from Electronic Annotation
more info
 
left/right axis specification ISS
Inferred from Sequence or Structural Similarity
more info
 
male gonad development IEA
Inferred from Electronic Annotation
more info
 
myoblast fusion IEA
Inferred from Electronic Annotation
more info
 
negative regulation of transcription from RNA polymerase II promoter IDA
Inferred from Direct Assay
more info
PubMed 
neuron migration IEA
Inferred from Electronic Annotation
more info
 
odontogenesis IMP
Inferred from Mutant Phenotype
more info
PubMed 
odontogenesis of dentin-containing tooth IEA
Inferred from Electronic Annotation
more info
 
patterning of blood vessels IEA
Inferred from Electronic Annotation
more info
 
positive regulation of DNA binding IEA
Inferred from Electronic Annotation
more info
 
positive regulation of myoblast proliferation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of transcription from RNA polymerase II promoter IDA
Inferred from Direct Assay
more info
PubMed 
prolactin secreting cell differentiation TAS
Traceable Author Statement
more info
PubMed 
pulmonary myocardium development IEA
Inferred from Electronic Annotation
more info
 
pulmonary vein morphogenesis IEA
Inferred from Electronic Annotation
more info
 
regulation of cell migration IEA
Inferred from Electronic Annotation
more info
 
regulation of transcription from RNA polymerase II promoter IDA
Inferred from Direct Assay
more info
 
regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
response to hormone IEA
Inferred from Electronic Annotation
more info
 
response to vitamin A IEA
Inferred from Electronic Annotation
more info
 
somatotropin secreting cell differentiation TAS
Traceable Author Statement
more info
PubMed 
spleen development ISS
Inferred from Sequence or Structural Similarity
more info
 
subthalamic nucleus development IEA
Inferred from Electronic Annotation
more info
 
superior vena cava morphogenesis IEA
Inferred from Electronic Annotation
more info
 
transcription from RNA polymerase II promoter IEA
Inferred from Electronic Annotation
more info
 
vascular smooth muscle cell differentiation IEA
Inferred from Electronic Annotation
more info
 
vasculogenesis IEA
Inferred from Electronic Annotation
more info
 
ventricular cardiac muscle cell development IEA
Inferred from Electronic Annotation
more info
 
ventricular septum morphogenesis IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytoplasm IEA
Inferred from Electronic Annotation
more info
 
nucleus IDA
Inferred from Direct Assay
more info
 
transcription factor complex IDA
Inferred from Direct Assay
more info
PubMed 
Preferred Names
pituitary homeobox 2
Names
pituitary homeobox 2
solurshin
all1-responsive gene 1
homeobox protein PITX2
ALL1-responsive protein ARP1
paired-like homeodomain transcription factor 2
rieg bicoid-related homeobox transcription factor 1

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_007120.1 

    Range
    230..24930
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000325.5NP_000316.2  pituitary homeobox 2 isoform c

    See proteins identical to NP_000316.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3), also known as ARP1c, lacks several exons at the 5' end and has an alternate 5' exon, as compared to variant 2. The resulting isoform (c) has a longer and distinct N-terminus, as compared to isoform b.
    Source sequence(s)
    AC017068, BC013998
    Consensus CDS
    CCDS3694.1
    UniProtKB/Swiss-Prot
    Q99697
    Related
    ENSP00000304169, OTTHUMP00000163738, ENST00000306732, OTTHUMT00000256310
    Conserved Domains (2) summary
    cd00086
    Location:93151
    homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.
    pfam03826
    Location:281299
    OAR; OAR domain
  2. NM_001204397.1NP_001191326.1  pituitary homeobox 2 isoform b

    See proteins identical to NP_001191326.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) has an additional exon in the 5' UTR, as compared to variant 2. Variants 2, 4 and 5 encode the same isoform b.
    Source sequence(s)
    AK127829, BC106010, BP372081, BX380370, U69961
    Consensus CDS
    CCDS3692.1
    UniProtKB/Swiss-Prot
    Q99697
    Related
    ENSP00000347004, OTTHUMP00000163736, ENST00000354925, OTTHUMT00000256308
    Conserved Domains (2) summary
    cd00086
    Location:86144
    homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.
    pfam03826
    Location:274292
    OAR; OAR domain
  3. NM_001204398.1NP_001191327.1  pituitary homeobox 2 isoform b

    See proteins identical to NP_001191327.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks an exon in the 5' UTR, as compared to variant 2. Variants 2, 4 and 5 encode the same isoform b.
    Source sequence(s)
    BC106010, BP372081
    Consensus CDS
    CCDS3692.1
    UniProtKB/Swiss-Prot
    Q99697
    Related
    ENSP00000481951, ENST00000614423
    Conserved Domains (2) summary
    cd00086
    Location:86144
    homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.
    pfam03826
    Location:274292
    OAR; OAR domain
  4. NM_001204399.1NP_001191328.1  pituitary homeobox 2 isoform a

    See proteins identical to NP_001191328.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) lacks an exon in the 5' UTR and an in-frame exon in the 5' CDS, as compared to variant 2. The resulting isoform (a) lacks an internal segment, as compared to isoform b. Variants 1 and 6 encode the same isoform a.
    Source sequence(s)
    BC106010, BP372081
    Consensus CDS
    CCDS3693.1
    UniProtKB/Swiss-Prot
    Q99697
    Conserved Domains (2) summary
    cd00086
    Location:4098
    homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.
    pfam03826
    Location:228246
    OAR; OAR domain
  5. NM_153426.2NP_700475.1  pituitary homeobox 2 isoform b

    See proteins identical to NP_700475.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2), also known as ARP1b, encodes the predominant isoform (b).
    Source sequence(s)
    AK127829, BC013998, BC106010, BP372081, BX380370, U69961
    Consensus CDS
    CCDS3692.1
    UniProtKB/Swiss-Prot
    Q99697
    Related
    ENSP00000484763, ENST00000613094
    Conserved Domains (2) summary
    cd00086
    Location:86144
    homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.
    pfam03826
    Location:274292
    OAR; OAR domain
  6. NM_153427.2NP_700476.1  pituitary homeobox 2 isoform a

    See proteins identical to NP_700476.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1), also known as ARP1a, lacks an in-frame exon in the 5' region, as compared to variant 2. The resulting isoform (a) lacks an internal segment, as compared to isoform b. Variants 1 and 6 encode the same isoform a.
    Source sequence(s)
    AK127829, BC106010, BP372081, BX380370, U69961
    Consensus CDS
    CCDS3693.1
    UniProtKB/Swiss-Prot
    Q99697
    Related
    ENSP00000484909, ENST00000616641
    Conserved Domains (2) summary
    cd00086
    Location:4098
    homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.
    pfam03826
    Location:228246
    OAR; OAR domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000004.12 

    Range
    110617423..110642123
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006714235.1XP_006714298.1  

    See proteins identical to XP_006714298.1

    UniProtKB/Swiss-Prot
    Q99697
    Related
    ENSP00000378097, OTTHUMP00000163734, ENST00000394598, OTTHUMT00000256306
    Conserved Domains (2) summary
    cd00086
    Location:86144
    homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.
    pfam03826
    Location:274292
    OAR; OAR domain

Alternate HuRef

Genomic

  1. AC_000136.1 

    Range
    107270120..107294817
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018915.2 

    Range
    111515486..111540182
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)