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

Summary

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: mouse all
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Genomic context

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_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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].
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.
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.
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.
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.
PHOX2A and PHOX2B genes are highly co-expressed in human neuroblastoma.
Title: PHOX2A and PHOX2B genes are highly co-expressed in human neuroblastoma.
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.
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

Associated conditions

Description	Tests
Fibrosis of extraocular muscles, congenital, 2 MedGen: C1865915 OMIM: 602078 GeneReviews: Congenital Fibrosis of the Extraocular Muscles Overview	not available

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

RH67903 (e-PCR)
- UniSTS:79363

PHOX2A_8209 (e-PCR)
- UniSTS:467830

RH48230 (e-PCR)
- UniSTS:37541

RH70700 (e-PCR)
- UniSTS:66799

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
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	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

Process	Evidence Code	Pubs
involved_in dopaminergic neuron differentiation	IC Inferred by Curator more info	PubMed
involved_in locus ceruleus development	IEA Inferred from Electronic Annotation more info
involved_in midbrain development	IEA Inferred from Electronic Annotation more info
involved_in noradrenergic neuron differentiation	IC Inferred by Curator more info	PubMed
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
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 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
involved_in somatic motor neuron differentiation	IEA Inferred from Electronic Annotation more info
involved_in 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

NG_008169.1 RefSeqGene

Range

5001..10100

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

Status: REVIEWED

Source sequence(s)

AP000593
NM_001425097.1 → NP_001412026.1 paired mesoderm homeobox protein 2A isoform 3

Status: REVIEWED

Source sequence(s)

AP000593
NM_001425098.1 → NP_001412027.1 paired mesoderm homeobox protein 2A isoform 4

Status: REVIEWED

Source sequence(s)

AP000593
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