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PHOX2A paired like homeobox 2A [ Homo sapiens (human) ]

Gene ID: 401, updated on 7-Apr-2025

Summary

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Official Symbol
PHOX2Aprovided by HGNC
Official Full Name
paired like homeobox 2Aprovided by HGNC
Primary source
HGNC:HGNC:691
See related
Ensembl:ENSG00000165462 MIM:602753; AllianceGenome:HGNC:691
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
ARIX; FEOM2; NCAM2; PMX2A; CFEOM2
Summary
The protein encoded by this gene contains a paired-like homeodomain most similar to that of the Drosophila aristaless gene product. The encoded protein plays a central role in development of the autonomic nervous system. It regulates the expression of tyrosine hydroxylase and dopamine beta-hydroxylase, two catecholaminergic biosynthetic enzymes essential for the differentiation and maintenance of the noradrenergic neurotransmitter phenotype. The encoded protein has also been shown to regulate transcription of the alpha3 nicotinic acetylcholine receptor gene. Mutations in this gene have been associated with autosomal recessive congenital fibrosis of the extraocular muscles. [provided by RefSeq, Jul 2008]
Expression
Biased expression in adrenal (RPKM 6.0) and appendix (RPKM 0.4) See more
Orthologs
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Genomic context

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See PHOX2A in Genome Data Viewer
Location:
11q13.4
Exon count:
3
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (72239077..72244176, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (72165694..72170794, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (71950121..71955220, complement)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene folate receptor alpha Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3714 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3715 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3716 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3717 Neighboring gene folate receptor beta Neighboring gene skeletal muscle cis-regulatory module in INPPL1 intron Neighboring gene inositol polyphosphate phosphatase like 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3718 Neighboring gene dedicator of cytokinesis 1 pseudogene Neighboring gene U2 small nuclear RNA auxiliary factor 1 like 4 pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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Related articles in PubMed

  1. A 5.5-Mb high-resolution integrated map of distal 11q13. Merscher S, et al. Genomics, 1997 Feb 1. PMID 9119371
  2. Phox2 genes - from patterning to connectivity. Brunet JF, et al. Curr Opin Genet Dev, 2002 Aug. PMID 12100889
  3. Congenital fibrosis of the extraocular muscles type 2, an inherited exotropic strabismus fixus, maps to distal 11q13. Wang SM, et al. Am J Hum Genet, 1998 Aug. PMID 9683611, Free PMC Article
  4. [Identification of a novel PHOX2A gene mutation in a Chinese family with congenital fibrosis of extraocular muscles type 2]. Dong JM, et al. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2012 Feb. PMID 22311481
  5. A novel PHOX2A/ARIX mutation in an Iranian family with congenital fibrosis of extraocular muscles type 2 (CFEOM2). Yazdani A, et al. Am J Ophthalmol, 2003 Nov. PMID 14597037

See all (39) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Outcomes of strabismus surgery in genetically confirmed congenital fibrosis of the extraocular muscles.
    Title: Outcomes of strabismus surgery in genetically confirmed congenital fibrosis of the extraocular muscles.
  2. PHOX2A expression is finely controlled during retinoic acid differentiation and this, together with PHOX2B down-regulation.
    Title: PHOX2A and PHOX2B are differentially regulated during retinoic acid-driven differentiation of SK-N-BE(2)C neuroblastoma cell line.
  3. Genetic linkage was found at 11q13 between D11S4151 and D11S1320 and the PHOX2A gene.
    Title: [Identification of a novel PHOX2A gene mutation in a Chinese family with congenital fibrosis of extraocular muscles type 2].
  4. Patients with ARIX and/or PHOX2B polymorphisms had less hypoplastic superior oblique muscles.
    Title: Phenotype-phenotype and genotype-phenotype correlations in patients with idiopathic superior oblique muscle palsy.
  5. Our 16-patient sample suggests that KIF21A and PHOX2A sequence variation does not have a role in common forms of congenital incomitant vertical strabismus.
    Title: Mutations in KIF21A and PHOX2A are absent in 16 patients with congenital vertical incomitant strabismus.
  6. Transfection of Phox2a cDNA significantly increases mRNA and protein levels of norepinephrine transporter and dopamine beta-hydroxylase.
    Title: Effects of transcription factors Phox2 on expression of norepinephrine transporter and dopamine beta-hydroxylase in SK-N-BE(2)C cells.
  7. PHOX2A gene, localized in a tumor suppressor candidate region at 11q, weas screened for mutations by DNA sequencing in 47 tumors of different stages.
    Title: The Phox2 pathway is differentially expressed in neuroblastoma tumors, but no mutations were found in the candidate tumor suppressor gene PHOX2A.
  8. PHOX2A and PHOX2B genes are highly co-expressed in human neuroblastoma.
    Title: PHOX2A and PHOX2B genes are highly co-expressed in human neuroblastoma.
  9. The ARIX 153G>A polymorphism might be a genetic risk factor for the development of congenital superior oblique muscle palsy
    Title: Clinical features, ARIX and PHOX2B nucleotide changes in three families with congenital superior oblique muscle palsy.
  10. Observational study of gene-disease association. (HuGE Navigator)
    Title: Sudden infant death syndrome: case-control frequency differences at genes pertinent to early autonomic nervous system embryologic development.
Submit: New GeneRIF Correction See all GeneRIFs (20)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

  • MGC52227

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA binding IEA
Inferred from Electronic Annotation
more info
  
enables DNA-binding transcription activator activity, RNA polymerase II-specific IDA
Inferred from Direct Assay
more info
 PubMed 
enables DNA-binding transcription activator activity, RNA polymerase II-specific IEA
Inferred from Electronic Annotation
more info
  
enables DNA-binding transcription factor activity NAS
Non-traceable Author Statement
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 IEA
Inferred from Electronic Annotation
more info
  
enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
Inferred from Sequence Alignment
more info
  
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding IDA
Inferred from Direct Assay
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 sequence-specific double-stranded DNA binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in dopaminergic neuron differentiation IC
Inferred by Curator
more info
 PubMed 
acts_upstream_of_or_within locus ceruleus development IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within midbrain development IEA
Inferred from Electronic Annotation
more info
  
involved_in noradrenergic neuron differentiation IC
Inferred by Curator
more info
 PubMed 
acts_upstream_of_or_within noradrenergic neuron differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in noradrenergic neuron differentiation NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in oculomotor nerve formation IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within parasympathetic nervous system development IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of DNA-templated transcription IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within regulation of respiratory gaseous exchange IEA
Inferred from Electronic Annotation
more info
  
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 
acts_upstream_of_or_within regulation of transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within somatic motor neuron differentiation IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within sympathetic nervous system development IEA
Inferred from Electronic Annotation
more info
  
involved_in trochlear nerve formation IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in chromatin IDA
Inferred from Direct Assay
more info
 PubMed 
located_in chromatin ISA
Inferred from Sequence Alignment
more info
  
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
paired mesoderm homeobox protein 2A
Names
ARIX1 homeodomain protein
aristaless homeobox homolog
aristaless homeobox protein homolog
arix homeodomain protein

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

  1. NG_008169.1 RefSeqGene

    Range
    5001..10100
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001425096.1 → NP_001412025.1  paired mesoderm homeobox protein 2A isoform 2

    Status: REVIEWED

    Source sequence(s)
    AP000593

  2. NM_001425097.1 → NP_001412026.1  paired mesoderm homeobox protein 2A isoform 3

    Status: REVIEWED

    Source sequence(s)
    AP000593

  3. NM_001425098.1 → NP_001412027.1  paired mesoderm homeobox protein 2A isoform 4

    Status: REVIEWED

    Source sequence(s)
    AP000593

  4. NM_005169.4 → NP_005160.2  paired mesoderm homeobox protein 2A isoform 1

    See identical proteins and their annotated locations for NP_005160.2

    Status: REVIEWED

    Source sequence(s)
    AK290645, BC041564
    Consensus CDS
    CCDS8214.1
    UniProtKB/Swiss-Prot
    A8K3N0, O14813, Q8IVZ2
    Related
    ENSP00000298231.5, ENST00000298231.5
    Conserved Domains (1) summary
    pfam00046
    Location:94 → 147
    Homeobox; Homeobox 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_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    72239077..72244176 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    72165694..72170794 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O14813.2 GenPept UniProtKB/Swiss-Prot:O14813

Gene LinkOut

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Chemical Information
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