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

Summary

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: mouse all
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Genomic context

Location:: 4q25

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (110617423..110642123, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (113919284..113943981, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (111538579..111563279, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
PITX2 induction leads to impaired cardiomyocyte function in arrhythmogenic cardiomyopathy.
Title: PITX2 induction leads to impaired cardiomyocyte function in arrhythmogenic cardiomyopathy.
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.
Genotype-phenotype association of PITX2 and FOXC1 in Axenfeld-Rieger syndrome.
Title: Genotype-phenotype association of PITX2 and FOXC1 in Axenfeld-Rieger syndrome.
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.
Decoding the PITX2-controlled genetic network in atrial fibrillation.
Title: Decoding the PITX2-controlled genetic network in atrial fibrillation.
Effect of PITX2 genetic variants on the susceptibility to stroke in the Chinese Han population.
Title: Effect of PITX2 genetic variants on the susceptibility to stroke in the Chinese Han population.

Submit: New GeneRIF Correction See all GeneRIFs (169)

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	Compare labs
Anterior segment dysgenesis 4 MedGen: C1842031 OMIM: 137600 GeneReviews: Not available	Compare labs
Axenfeld-Rieger syndrome type 1 MedGen: C3714873 OMIM: 180500 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 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 EBI GWAS CatalogPubMed
Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies six new susceptibility loci for atrial fibrillation. EBI GWAS Catalog EBI GWAS CatalogPubMed
Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants. EBI GWAS Catalog EBI GWAS CatalogPubMed
Variants conferring risk of atrial fibrillation on chromosome 4q25. EBI GWAS Catalog EBI GWAS CatalogPubMed
Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Pitx2 (e-PCR), detects polymorphism
- UniSTS:507415

PITX2_380 (e-PCR)
- UniSTS:277586

D4S3305 (e-PCR)
- UniSTS:47798

SHGC-50188 (e-PCR)
- UniSTS:81619

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 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 protein binding	IPI Inferred from Physical Interaction 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 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 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
part_of 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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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

NG_007120.1 RefSeqGene

Range

19276..24930

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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
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
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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

110617423..110642123 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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