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

Gene ID: 5308, updated on 2-Nov-2024

Summary

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Official Symbol
PITX2provided by HGNC
Official Full Name
paired like homeodomain 2provided by HGNC
Primary source
HGNC:HGNC:9005
See related
Ensembl:ENSG00000164093 MIM:601542; AllianceGenome:HGNC:9005
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; ASGD4; 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]
Expression
Biased expression in placenta (RPKM 15.1), urinary bladder (RPKM 3.5) and 6 other tissues See more
Orthologs
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Genomic context

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See PITX2 in Genome Data Viewer
Location:
4q25
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (110617423..110642123, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (113919284..113943981, complement)
RS_2024_09 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 ATAC-STARR-seq lymphoblastoid active region 21817 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_72001 Neighboring gene glutamyl aminopeptidase Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_72004 Neighboring gene Sharpr-MPRA regulatory region 9284 Neighboring gene uncharacterized LOC105377363 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:111537217-111537875 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:111540229-111540882 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:111540883-111541534 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:111542189-111542841 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15630 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:111547605-111548106 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:111548107-111548606 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr4:111549504-111550355 Neighboring gene PITX2 adjacent non-coding RNA Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:111553473-111553985 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:111559017-111559517 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:111560253-111560848 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr4:111562143-111562646 Neighboring gene uncharacterized LOC124900857 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:111614011-111614566 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_72035 Neighboring gene VISTA enhancer hs930 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:111715278-111715811 Neighboring gene microRNA 297

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. PITX2 DNA Methylation as Biomarker for Individualized Risk Assessment of Prostate Cancer in Core Biopsies. Uhl B, et al. J Mol Diagn, 2017 Jan. PMID 27939865
  2. Usefulness of single nucleotide polymorphism in chromosome 4q25 to predict in-hospital and long-term development of atrial fibrillation and survival in patients undergoing coronary artery bypass grafting. Virani SS, et al. Am J Cardiol, 2011 May 15. PMID 21414601, Free PMC Article
  3. PITX2 Loss-of-Function Mutation Contributes to Congenital Endocardial Cushion Defect and Axenfeld-Rieger Syndrome. Zhao CM, et al. PLoS One, 2015. PMID 25893250, Free PMC Article
  4. Truncation of PITX2 differentially affects its activity on physiological targets. Quentien MH, et al. J Mol Endocrinol, 2011 Feb. PMID 20978111
  5. Paired-like Homeodomain Transcription factor 2 expression by breast cancer bone marrow disseminated tumor cells is associated with early recurrent disease development. Pillai SG, et al. Breast Cancer Res Treat, 2015 Oct. PMID 26400846, Free PMC Article

See all (224) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. PITX2 functions as a transcription factor for GPX4 and protects pancreatic cancer cells from ferroptosis.
    Title: PITX2 functions as a transcription factor for GPX4 and protects pancreatic cancer cells from ferroptosis.
  2. Intergenic sequences harboring potential enhancer elements contribute to Axenfeld-Rieger syndrome by regulating PITX2.
    Title: Intergenic sequences harboring potential enhancer elements contribute to Axenfeld-Rieger syndrome by regulating PITX2.
  3. Exploring the association between PITX2, third molars agenesis and sella turcica morphology : PITX2, third molars agenesis and sella turcica morphology.
    Title: Exploring the association between PITX2, third molars agenesis and sella turcica morphology : PITX2, third molars agenesis and sella turcica morphology.
  4. Enamel defects of Axenfeld-Rieger syndrome and the role of PITX2 in its pathogenesis.
    Title: Enamel defects of Axenfeld-Rieger syndrome and the role of PITX2 in its pathogenesis.
  5. Pulmonary Vein Myocardial Sleeve Length and its Association With Sex and 4q25/PITX2 Genotype.
    Title: Pulmonary Vein Myocardial Sleeve Length and its Association With Sex and 4q25/PITX2 Genotype.
  6. PITX2 Knockout Induces Key Findings of Electrical Remodeling as Seen in Persistent Atrial Fibrillation.
    Title: PITX2 Knockout Induces Key Findings of Electrical Remodeling as Seen in Persistent Atrial Fibrillation.
  7. PITX2 induction leads to impaired cardiomyocyte function in arrhythmogenic cardiomyopathy.
    Title: PITX2 induction leads to impaired cardiomyocyte function in arrhythmogenic cardiomyopathy.
  8. Association Between rs2200733 Polymorphism of PITX2 Gene and the Risk of Atrial Fibrillation.
    Title: Association Between rs2200733 Polymorphism of PITX2 Gene and the Risk of Atrial Fibrillation.
  9. Genotype-phenotype association of PITX2 and FOXC1 in Axenfeld-Rieger syndrome.
    Title: Genotype-phenotype association of PITX2 and FOXC1 in Axenfeld-Rieger syndrome.
  10. Comparison of Anterior Segment Abnormalities in Individuals With FOXC1 and PITX2 Variants.
    Title: Comparison of Anterior Segment Abnormalities in Individuals With FOXC1 and PITX2 Variants.
Submit: New GeneRIF Correction See all GeneRIFs (171)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Anophthalmia-microphthalmia syndrome
MedGen: C5680330 GeneReviews: Not available
not available
Anterior segment dysgenesis 4
MedGen: C1842031 OMIM: 137600 GeneReviews: Not available
not available
Axenfeld-Rieger syndrome type 1
MedGen: C3714873 OMIM: 180500 GeneReviews: Not available
not available
Ring dermoid of cornea
MedGen: C1867155 OMIM: 180550 GeneReviews: Not available
not available

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2022-10-24)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated 2022-10-24)

ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Common variants in KCNN3 are associated with lone atrial fibrillation.
EBI GWAS Catalog
Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies.
EBI GWAS Catalog
Meta-analysis identifies six new susceptibility loci for atrial fibrillation.
EBI GWAS Catalog
Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.
EBI GWAS Catalog
Variants conferring risk of atrial fibrillation on chromosome 4q25.
EBI GWAS Catalog
Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry.
EBI GWAS Catalog

Variation

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See Variation Viewer (GRCh37.p13)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC20144, MGC111022

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA-binding transcription factor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
Inferred from Biological aspect of Ancestor
more info
  
enables DNA-binding transcription factor activity, RNA polymerase II-specific IDA
Inferred from Direct Assay
more info
 PubMed 
enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
Inferred from Sequence Alignment
more info
  
enables DNA-binding transcription factor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables DNA-binding transcription repressor activity, RNA polymerase II-specific IDA
Inferred from Direct Assay
more info
 PubMed 
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables RNA polymerase II-specific DNA-binding transcription factor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables phosphoprotein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ribonucleoprotein complex binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables sequence-specific double-stranded DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables transcription cis-regulatory region binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in anatomical structure morphogenesis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in camera-type eye development IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cardiac neural crest cell migration involved in outflow tract morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in deltoid tuberosity development IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in determination of left/right symmetry ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in embryonic heart tube left/right pattern formation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in hair cell differentiation IC
Inferred by Curator
more info
 PubMed 
involved_in iris morphogenesis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in left/right axis specification ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
  
involved_in odontogenesis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in outflow tract morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of cell population proliferation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in prolactin secreting cell differentiation TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of DNA-templated transcription IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in somatotropin secreting cell differentiation TAS
Traceable Author Statement
more info
 PubMed 
involved_in spleen development ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
located_in chromatin ISA
Inferred from Sequence Alignment
more info
  
located_in cytoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
part_of transcription regulator complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
pituitary homeobox 2
Names
ALL1-responsive protein ARP1
all1-responsive gene 1
homeobox protein PITX2
paired-like homeodomain transcription factor 2
rieg bicoid-related homeobox transcription factor 1
solurshin

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

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 RefSeqGene

    Range
    19276..24930
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000325.6 → NP_000316.2  pituitary homeobox 2 isoform c

    See identical proteins and their annotated locations for 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/TrEMBL
    A0A8J9C2I7
    Related
    ENSP00000495061.1, ENST00000644743.1
    Conserved Domains (3) summary
    COG5576
    Location:40 → 149
    COG5576; Homeodomain-containing transcription factor [Transcription]
    pfam00046
    Location:96 → 149
    Homeobox; Homeobox domain
    pfam03826
    Location:282 → 299
    OAR; OAR domain

  2. NM_001204397.2 → NP_001191326.1  pituitary homeobox 2 isoform b

    See identical proteins and their annotated locations for 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)
    AC017068
    Consensus CDS
    CCDS3692.1
    UniProtKB/Swiss-Prot
    A8K6C6, B2RA02, B3KXS0, O60578, O60579, O60580, Q3KQX9, Q99697, Q9BY17
    UniProtKB/TrEMBL
    D6RFI4
    Related
    ENSP00000347004.2, ENST00000354925.6
    Conserved Domains (2) summary
    pfam00046
    Location:89 → 142
    Homeobox; Homeobox domain
    pfam03826
    Location:275 → 292
    OAR; OAR domain

  3. NM_001204398.1 → NP_001191327.1  pituitary homeobox 2 isoform b

    See identical proteins and their annotated locations for 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
    A8K6C6, B2RA02, B3KXS0, O60578, O60579, O60580, Q3KQX9, Q99697, Q9BY17
    UniProtKB/TrEMBL
    D6RFI4
    Related
    ENSP00000421454.1, ENST00000511837.5
    Conserved Domains (2) summary
    pfam00046
    Location:89 → 142
    Homeobox; Homeobox domain
    pfam03826
    Location:275 → 292
    OAR; OAR domain

  4. NM_001204399.1 → NP_001191328.1  pituitary homeobox 2 isoform a

    See identical proteins and their annotated locations for 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/TrEMBL
    A0A8J9C2I7
    Conserved Domains (2) summary
    pfam00046
    Location:43 → 96
    Homeobox; Homeobox domain
    pfam03826
    Location:229 → 246
    OAR; OAR domain

  5. NM_153426.3 → NP_700475.1  pituitary homeobox 2 isoform b

    See identical proteins and their annotated locations for NP_700475.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2), also known as ARP1b, encodes the predominant isoform (b).
    Source sequence(s)
    AC017068
    Consensus CDS
    CCDS3692.1
    UniProtKB/Swiss-Prot
    A8K6C6, B2RA02, B3KXS0, O60578, O60579, O60580, Q3KQX9, Q99697, Q9BY17
    UniProtKB/TrEMBL
    D6RFI4
    Related
    ENSP00000378095.4, ENST00000394595.8
    Conserved Domains (2) summary
    pfam00046
    Location:89 → 142
    Homeobox; Homeobox domain
    pfam03826
    Location:275 → 292
    OAR; OAR domain

  6. NM_153427.3 → NP_700476.1  pituitary homeobox 2 isoform a

    See identical proteins and their annotated locations for 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)
    AC017068
    Consensus CDS
    CCDS3693.1
    UniProtKB/TrEMBL
    A0A8J9C2I7
    Related
    ENSP00000347192.5, ENST00000355080.9
    Conserved Domains (2) summary
    pfam00046
    Location:43 → 96
    Homeobox; Homeobox domain
    pfam03826
    Location:229 → 246
    OAR; OAR domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

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

mRNA and Protein(s)

  1. XM_024454090.2 → XP_024309858.1  pituitary homeobox 2 isoform X1

    Related
    ENST00000645131.1
    Conserved Domains (2) summary
    pfam00046
    Location:2 → 31
    Homeobox; Homeobox domain
    pfam03826
    Location:164 → 181
    OAR; OAR domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    113919284..113943981 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054350186.1 → XP_054206161.1  pituitary homeobox 2 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q99697.2 GenPept UniProtKB/Swiss-Prot:Q99697

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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