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PHOX2A Gene

protein-coding GIFtS: 55
GCID: GC11M071950

Paired-Like Homeobox 2a

(Previous names: aristaless (Drosophila) homeobox, aristaless homeobox (Drosophila),...)
(Previous symbols: ARIX, FEOM2)

See related diseases
at

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Paired-Like Homeobox 2a¹ ² ³		Aristaless (Drosophila) Homeobox, Aristaless Homeobox (Drosophila), Fibrosis Of Extraocular Muscles, Congenital, 2, Autosomal Recessive¹
ARIX¹ ² ³ ⁵		Paired-Like (Aristaless) Homeobox 2a¹
FEOM2¹ ²		NCAM2²
Aristaless Homeobox Protein Homolog² ³		Aristaless Homeobox Homolog²
PMX2A² ³		Arix Homeodomain Protein²
ARIX1 Homeodomain Protein² ³		Paired Mesoderm Homeobox Protein 2A²
CFEOM2² ⁵

External Ids:	HGNC: 691¹	Entrez Gene: 401²	Ensembl: ENSG00000165462⁷	OMIM: 602753⁵	UniProtKB: O14813³

Export aliases for PHOX2A gene to outside databases

Previous GC identifers: GC11M073490 GC11M072172 GC11M071676 GC11M071627 GC11M068243

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for PHOX2A Gene:

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)

GeneCards Summary for PHOX2A Gene:

PHOX2A (paired-like homeobox 2a) is a protein-coding gene. Diseases associated with PHOX2A include congenital fibrosis of the extraocular muscles 2, and paralytic squint. GO annotations related to this gene include RNA polymerase II regulatory region sequence-specific DNA binding and sequence-specific DNA binding transcription factor activity. An important paralog of this gene is ALX1.

UniProtKB/Swiss-Prot: PHX2A_HUMAN, O14813

Function: May be involved in regulating the specificity of expression of the catecholamine biosynthetic genes.

Acts as a transcription activator/factor. Could maintain the noradrenergic phenotype

Gene Wiki entry for PHOX2A Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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Regulatory elements:

Regulatory transcription factor binding sites in the PHOX2A gene promoter:
GATA-3 Pax-5 AP-2alpha isoform 3 Nkx2-5 AP-2alpha isoform 2 GATA-2 GATA-1 AP-2alpha isoform 4 AP-2alpha AP-2alphaA
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: PHOX2A promoter sequence

Search Chromatin IP Primers for PHOX2A

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat PHOX2A

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 11q13.2 Ensembl cytogenetic band: 11q13.4 HGNC cytogenetic band: 11q13.4

PHOX2A Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
PHOX2A gene location

GeneLoc information about chromosome 11 GeneLoc Exon Structure

GeneLoc location for GC11M071950: view genomic region (about GC identifiers)

Start:	71,950,121 bp from pter	End:	71,956,708 bp from pter
Size:	6,588 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: PHX2A_HUMAN, O14813 (See protein sequence)

Recommended Name: Paired mesoderm homeobox protein 2A

Size: 284 amino acids; 29653 Da

Secondary accessions: A8K3N0 Q8IVZ2

Explore the universe of human proteins at neXtProt for PHOX2A: NX_O14813

Explore proteomics data for PHOX2A at MOPED

Post-translational modifications:

Modification sites at neXtProt

Modification sites at PhosphoSitePlus

See PHOX2A Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_005160.2

ENSEMBL proteins:

ENSP00000444845 ENSP00000298231

PHOX2A Human Recombinant Protein Products:

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	Cloud-Clone Corp. Proteins for PHOX2A

PHOX2A Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of PHOX2A
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	Novus Biologicals PHOX2A Antibodies
	Abcam antibodies for PHOX2A
	Cloud-Clone Corp. Antibodies for PHOX2A
	ThermoFisher Antibody for PHOX2A
	LSBio Antibodies in human, mouse, rat for PHOX2A

PHOX2A Assay Products:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Assay Services for PHOX2A
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	Cloud-Clone Corp. ELISAs for PHOX2A Cloud-Clone Corp. CLIAs for PHOX2A

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:

PRD: Homeoboxes / PRD class

3 InterPro protein domains:

IPR017970 Homeobox_CS

IPR001356 Homeobox_dom

IPR009057 Homeodomain-like

Graphical View of Domain Structure for InterPro Entry O14813

ProtoNet protein and cluster: O14813

1 Blocks protein domain: IPB000047 Lambda and other repressor helix-turn-helix signature

UniProtKB/Swiss-Prot: PHX2A_HUMAN, O14813

Similarity: Belongs to the paired homeobox family

Similarity: Contains 1 homeobox DNA-binding domain

PHOX2A for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: PHX2A_HUMAN, O14813

Function: May be involved in regulating the specificity of expression of the catecholamine biosynthetic genes.

Acts as a transcription activator/factor. Could maintain the noradrenergic phenotype

Gene Ontology (GO): 4 molecular function terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000977	RNA polymerase II regulatory region sequence-specific DNA binding	IDA	16280598
GO:0003677	DNA binding	--	--
GO:0003700	sequence-specific DNA binding transcription factor activity	IEA	--
GO:0043565	sequence-specific DNA binding	--	--

PHOX2A for ontologies About GeneDecksing

Phenotypes:
8 MGI mutant phenotypes (inferred from 6 alleles) (MGI details for Phox2a):

behavior/neurological	cellular	growth/size/body	homeostasis/metabolism	mortality/aging
nervous system	no phenotypic analysis	respiratory system

PHOX2A for phenotypes About GeneDecksing

Animal Models:
MGI mouse knock-outs for PHOX2A: Phox2a^tm1Jbr Phox2a/Inppl1^{Phox2a/tm1Ssch}

inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for PHOX2A

inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for PHOX2A

genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for PHOX2A

genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for PHOX2A

Transcription Factor Targeting:

Targeting motifs: HOMER Transcription Factor Regulatory Elements motif viewer

Consensus sequence: YTAATYNRATTA

miRNA Products:		miRTarBase miRNAs that target PHOX2A: hsa-mir-181a-5p (MIRT025054), hsa-mir-122-5p (MIRT023218)

		Block miRNA regulation of human, mouse, rat PHOX2A using miScript Target Protectors
		7 qRT-PCR Assays for microRNAs that regulate PHOX2A:
		hsa-miR-607 hsa-miR-4254 hsa-miR-330-5p hsa-miR-326 hsa-miR-486-3p hsa-miR-1224-5p hsa-miR-1305
		SwitchGear 3'UTR luciferase reporter plasmid: PHOX2A 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for PHOX2A
		Predesigned siRNA for gene silencing in human, mouse, rat PHOX2A

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for PHOX2A

Clone Products:		OriGene clones in human, mouse for PHOX2A (see all 5) OriGene ORF clones in mouse, rat for PHOX2A OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: PHOX2A (NM_005169)
		Browse Sino Biological Human cDNA Clones
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for PHOX2A
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PHOX2A

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for PHOX2A
		Browse ESI BIO Cell Lines and PureStem Progenitors for PHOX2A

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for PHOX2A

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

PHX2A_HUMAN, O14813: Nucleus (By similarity)

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
nucleus	4

About this image

Gene Ontology (GO): 2 cellular component terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000790	nuclear chromatin	IDA	16280598
GO:0005634	nucleus	--	--

PHOX2A for ontologies About GeneDecksing

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for PHOX2A About

See pathways by source

SuperPath

Contained pathways About

SIDS Susceptibility Pathways

SIDS Susceptibility Pathways

1 BioSystems Pathway for PHOX2A

SIDS Susceptibility Pathways

Custom Pathway & Disease-focused RT² Profiler PCR Arrays for PHOX2A
Interactions:

GeneGlobe Interaction Network for PHOX2A

STRING Interaction Network Preview (showing 5 interactants - click image to see 10)

Selected Interacting proteins for PHOX2A (O14813³ ENSP00000298231⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 13)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
ATF6B	Q99941³, ENSP00000364349⁴	I2D: score=1 STRING: ENSP00000364349
ENSG00000168468	Q99941³	I2D: score=1
ENSG00000228628	Q99941³	I2D: score=1
ENSG00000234539	Q99941³	I2D: score=1
HAND2	P61296³, ENSP00000352565⁴	I2D: score=2 STRING: ENSP00000352565

About this table

Gene Ontology (GO): Selected biological process terms (see all 13): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003357	noradrenergic neuron differentiation	NAS	16280598
GO:0006351	transcription, DNA-templated	IEA	--
GO:0006355	regulation of transcription, DNA-templated	--	--
GO:0021523	somatic motor neuron differentiation	IEA	--
GO:0021623	oculomotor nerve formation	IEA	--

PHOX2A for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Browse Tocris compounds for PHOX2A (PHX2A)

3 Novoseek inferred chemical compound relationships for PHOX2A gene About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
dopamine	45.9	4	16280598 (1), 14506227 (1), 18572378 (1)
norepinephrine	44.2	2	14512028 (1), 16280598 (1)
tyrosine	26.1	2	8613746 (1), 10624949 (1)

PHOX2A for compounds About GeneDecksing

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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REFSEQ mRNAs for PHOX2A gene:

NM_005169.3

3 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000546310 ENST00000298231(uc001osh.4) ENST00000544057

miRNA Products:		Block miRNA regulation of human, mouse, rat PHOX2A using miScript Target Protectors
		7 qRT-PCR Assays for microRNAs that regulate PHOX2A:
		hsa-miR-607 hsa-miR-4254 hsa-miR-330-5p hsa-miR-326 hsa-miR-486-3p hsa-miR-1224-5p hsa-miR-1305
		SwitchGear 3'UTR luciferase reporter plasmid: PHOX2A 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for PHOX2A
		Predesigned siRNA for gene silencing in human, mouse, rat PHOX2A

Clone Products:		OriGene clones in human, mouse for PHOX2A (see all 5) OriGene ORF clones in mouse, rat for PHOX2A OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: PHOX2A (NM_005169)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for PHOX2A
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PHOX2A

Primer Products:		OriGene qPCR primer pairs and template standards for PHOX2A OriGene qSTAR qPCR primer pairs in human, mouse for PHOX2A
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat PHOX2A
		QuantiTect SYBR Green Assays in human, mouse, rat PHOX2A
		QuantiFast Probe-based Assays in human, mouse, rat PHOX2A

Selected AceView cDNA sequences (see all 28):

CR621077 BQ899131 CR593042 BC041564 CR590341 CR607218 CR596068 CR600761

CR604478 CR607262 BU151137 NM_005169 BE383103 BX375756 AL522064 AL529571

BQ881657 BQ890461 BI196975 BX376662 BF310680 BF311651 BE313749 BQ070957

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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PHOX2A expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: AGGCCTGTCC

About this image

PHOX2A expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 2) fully expand


Neural Tube (Nervous System)
Metencephalon

Brain (Nervous System)
Cerebellum

PHOX2A Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

PHOX2A Protein Expression

Custom PCR Arrays for PHOX2A

Primer Products:		OriGene qPCR primer pairs and template standards for PHOX2A OriGene qSTAR qPCR primer pairs in human, mouse for PHOX2A
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat PHOX2A
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		QuantiFast Probe-based Assays in human, mouse, rat PHOX2A

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for PHOX2A

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of animals.

Orthologs for PHOX2A gene from Selected species (see all 12) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Phox2a^{1 , 5}	paired-like homeobox 2a^{1, 5}	91.19(n)¹ 97.86(a)¹		7 (54.66 cM)⁵ 11859¹ NM_008887.2¹ NP_032913.1¹ 101818313⁵
lizard (Anolis carolinensis)	Reptilia	--	Uncharacterized protein	35(a)	many ↔ many	6(80382567-80417205)
tropical clawed frog (Xenopus tropicalis)	Amphibia	phox2a¹	paired-like homeobox 2a	67.64(n) 69.09(a)		100486496 NM_001252199.1 NP_001239128.1
zebrafish (Danio rerio)	Actinopterygii	phox2a¹	paired-like homeobox 2a	70.16(n) 67.87(a)		404602 NM_207070.1 NP_996953.1
fruit fly (Drosophila melanogaster)	Insecta	PHDP⁶	Putative homeodomain protein	34(a)	1 → many	2R(19770708-19771835)
worm (Caenorhabditis elegans)	Secernentea	ceh-17⁶	Protein CEH-17 (ceh-17) mRNA, complete cds	34(a)	1 → many	I(4568962-4570027) WBGene00000440

ENSEMBL Gene Tree for PHOX2A (if available)
TreeFam Gene Tree for PHOX2A (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for PHOX2A gene

ALX1² PHOX2B² ARX² RAX² DRGX² SHOX2² PRRX1² ALX4²

ISX² RAX2² ALX3² SHOX² OTP² PRRX2²

6 SIMAP similar genes for PHOX2A using alignment to 3 protein entries: PHX2A_HUMAN (see all proteins):

PRRX1 PHOX2B PRRX2 DRGX ARX OTP

PHOX2A for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr 11 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
VAR_019014⁴		Congenital fibrosis of extraocular muscles 2 (CFEOM2)⁴	--	see VAR_019014	2	A V	mis⁴		0	--	--	--	--
rs104894269^1,2	C	pathogenic¹	71818464(-)	`CTCGGC/TAGGTG`	2	A V	mis¹		0	--	--	--	--
rs145380401^1,2	C	--	71815908(+)	`ATGCGC/TCGCTG`	2	R	syn¹		0	--	--	--	--
rs200316334^1,2	C	--	71815970(+)	`TGCGGA/GTGTGT`	1	--	int¹		0	--	--	--	--
rs201136687^1,2		--	71815976(+)	`TGTGTG/TCAGGG`	1	--	int¹		0	--	--	--	--
rs187290180^1,2		--	71816390(+)	`CTGTCA/CGGTCT`	1	--	int¹		0	--	--	--	--
rs34220595^1,2	C	--	71816429(+)	`CAGTTC/ATGGGC`	1	--	int¹		2		NA	4
rs117476547^1,2	C,F	--	71816627(+)	`CTCTTC/ACTAAT`	1	--	int¹		1		NA	120
rs147658512^1,2		--	71816864(+)	`CCCCAC/TAGGTA`	1	--	int¹		0	--	--	--	--
rs141460435^1,2	C	--	71817017(+)	`ATCTTC/TGTCAT`	1	--	int¹		0	--	--	--	--
rs190931065^1,2		--	71817057(+)	`CGCCTC/GATACT`	1	--	int¹		0	--	--	--	--
rs146997548^1,2		--	71817070(+)	`TCTCTA/TTCTCC`	1	--	int¹		0	--	--	--	--
rs11601523^1,2	C,H	--	71817102(+)	`TCCTAG/TGATTT`	1	--	int¹		1		NA	2
rs35803854^1,2	C,F,H	--	71817308(+)	`CCAGCC/TTAGGG`	1	--	int¹		3		NS NA	282
rs199834841^1,2	C	--	71817334(+)	`CTTCT-/TCTTC TTTTT`	1	--	int¹		0	--	--	--	--
rs141537121^1,2		--	71817335(+)	`TTCTT-/CTTC TTTTT`	1	--	int¹		0	--	--	--	--
rs182636514^1,2		--	71817458(+)	`CCCAAA/GTAGCT`	1	--	int¹		0	--	--	--	--
rs33910008^1,2	C	--	71817498(+)	`GCTAA-/T/TT TTTTT`	1	--	int¹		2		NA CSA	4
rs186351901^1,2		--	71817633(+)	`ACCGCA/GCCTGG`	1	--	int¹		0	--	--	--	--
rs189989605^1,2	C	--	71817884(+)	`AAAACC/TCGGGC`	1	--	int¹		0	--	--	--	--
rs71477720^1,2	C,F	--	71818117(+)	`CTGGGG/AGCCTT`	1	--	int¹		2		NA	4
rs117774231^1,2	C,F	--	71818154(+)	`TTTAGT/CGGTCA`	1	--	int¹		1		NA	120
rs78268306^1,2	C,F	--	71818172(+)	`CAGGTG/CGTGAG`	1	--	int¹		2		WA EA	238
rs182932220^1,2	C	--	71818523(+)	`GAGCCA/GAGCGC`	2	L	syn¹		0	--	--	--	--
rs12418533^1,2	C,F,H	--	71819332(+)	`GAAGGG/AGGATG`	1	--	us2k¹ trp³		16		NS EA NA CSA WA	2220
rs187486053^1,2		--	71819346(+)	`ACCGGA/GAAGAG`	1	--	us2k¹		0	--	--	--	--
rs117191780^1,2	C,F	--	71819408(+)	`GAGACC/AGGGAG`	1	--	us2k¹		1		NA	120
rs139959739^1,2	C	--	71819604(+)	`GAGAC-/AAGAGGA`	1	--	us2k¹		0	--	--	--	--
rs76331746^1,2	F	--	71819838(+)	`GAAAAC/TGCCTC`	1	--	us2k¹		1		WA	118
rs3132788^1,2	C,F,H	--	71819956(+)	`CAGGTC/TCCTCT`	1	--	us2k¹		9		NS EA WA NA	924
rs150139052^1,2		--	71820158(+)	`CAGGGC/TCCCCC`	1	--	us2k¹		0	--	--	--	--
rs7110260^1,2	C,F,A,H	--	71820244(+)	`AGCTCC/TCTCGT`	1	--	us2k¹		17		NS EA NA WA	2338
rs138133808^1,2	C	--	71820350(+)	`TCAAC-/CCCCAG CCCCA`	1	--	cds¹		0	--	--	--	--
rs138500249^1,2		--	71820521(+)	`CCTCTC/TCTCAG`	1	--	us2k¹		0	--	--	--	--
rs78580101^1,2	F	--	71820538(+)	`CTTCCC/GCCATC`	1	--	us2k¹		1		WA	118
rs12802737^1,2	C	--	71820551(+)	`CCGTTC/TTGGGC`	1	--	us2k¹		1		NA	2
rs677685^1,2	C,F,A,H	--	71820560(-)	`TCCTGC/GGAAGC`	1	--	us2k¹		16		NS EA NA WA CSA	963
rs76222828^1,2	C,F	--	71820582(+)	`CCCCAA/GTCTCC`	1	--	us2k¹		1		NA	120
rs191996718^1,2		--	71820613(+)	`GATTTC/TTTTGA`	1	--	us2k¹		0	--	--	--	--
rs184084377^1,2		--	71820679(+)	`ATAAAA/GTTTAC`	1	--	us2k¹		0	--	--	--	--
rs12807696^1,2	C,F,H	--	71820783(+)	`aaaatC/Taaaac`	1	--	us2k¹		11		NS EA NA	1306
rs200556921^1,2		--	71951160(+)	`TTTTG-/GCG CCCGCCGCGCC`	1	--	cds¹		0	--	--	--	--
rs117423657^1,2	C,F	--	71951312(+)	`CGCAAG/AGCTCG`	1	--	int¹		1		EA	120
rs139842297^1,2	C	--	71951328(+)	`GATCCC/TGGTTC`	1	--	int¹		0	--	--	--	--
rs182039003^1,2		--	71951510(+)	`GGGGAA/CCCTGC`	1	--	int¹		0	--	--	--	--
rs149822880^1,2	C	--	71951692(+)	`ACAAAC/TAGACA`	1	--	int¹		0	--	--	--	--
rs72968872^1,2	C,F	--	71951999(+)	`CCTGCT/GGCCTC`	1	--	int¹		1		WA	118
rs145786343^1,2	C	--	71952035(+)	`CCGCGC/GCCTGC`	1	--	int¹		0	--	--	--	--
rs79908580^1,2	F	--	71952045(+)	`CCTTCG/CGGCTG`	1	--	int¹		1		WA	118
rs148949510^1,2		--	71952077(+)	`CCCCAA/GGTGTT`	1	--	int¹		0	--	--	--	--
rs140850664^1,2	C	--	71955067(+)	`GGGGGC/TGGGGG`	1	--	ut5¹		0	--	--	--	--
rs200284055^1,2		--	71955098(+)	`GTCGGA/GGTCCG`	1	--	ut5¹		0	--	--	--	--
rs71062759^1,2	C	--	71957208(-)	`CTGAAA/-AAAAA`	1	--	us2k¹		1		NA	2
VAR_019016⁴		--	--	see VAR_019016	2	P Q	mis⁴		0	--	--	--	--
rs201580701^1,2	--	--	71951878(+)	`CCTCGG/TCCTCC`	1	--	int¹		0	--	--	--	--
rs369751238^1,2	--	--	71950765(+)	`GGGGGC/TAGGCT`	1	--	ut3¹		0	--	--	--	--
rs374141512^1,2	--	--	71819988(+)	`CACACA/GACCTT`	1	--	us2k¹		0	--	--	--	--
rs374500870^1,2	--	--	71815992(+)	`GGGGGC/GGGGGC`	1	--	int¹		0	--	--	--	--
rs148937033^1,2	--	--	71815928(+)	`CTCGTG/ACAGGC`	2	/H /Y	mis¹		1		NA	4534
rs374198327^1,2	--	--	71950799(+)	`TAGAAC/GAGATT`	2	L	syn¹		0	--	--	--	--
rs376482990^1,2	--	--	71815833(+)	`TAAATA/GTCGGG`	2	D	syn¹		0	--	--	--	--
rs112895601^1,2	--	--	71951606(+)	`TGGAGC/AGCAGT`	1	--	int¹		1		CSA	2
rs111678033^1,2	--	--	71816323(+)	`TCCGAC/TCCTTC`	1	--	int¹		1		CSA	2
rs369607302^1,2	--	--	71816652(+)	`ATCTC-/TCTTCAAC`	1	--	int¹		0	--	--	--	--
rs34663656^1,2	--	--	71951653(+)	`GTCAA-/GGCGGG`	1	--	int¹		0	--	--	--	--
rs373067213^1,2	--	--	71815986(+)	`GGGCC-/GGGGGG`	1	--	int¹		0	--	--	--	--
rs113560811^1,2	--	--	71818104(+)	`TGATAG/AGGCTG`	1	--	int¹		1		CSA	2
rs34910878^1,2	--	--	71820868(+)	`TTGTG-/TTTTTT`	1	--	us2k¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for PHOX2A (71950121 - 71956708 bp)

Structural Variations
Database of Genomic Variants (DGV) 2 variations for PHOX2A: About this table

Variant ID	Type	Subtype	PubMed ID
esv26290	CNV	Loss	19812545
dgv1221n71	CNV	Loss	21882294

Human Gene Mutation Database (HGMD): PHOX2A

Site Specific Mutation Identification with PCR Assays

SeqTarget long-range PCR primers for resequencing PHOX2A

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 602753
OMIM disorders: 602078
UniProtKB/Swiss-Prot: PHX2A_HUMAN, O14813

Congenital fibrosis of extraocular muscles 2 (CFEOM2) [MIM:602078]: A congenital ocular motility disorder

marked by restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear

nerves. It is clinically characterized by anchoring of the eyes in downward gaze, ptosis, and backward tilt of

the head. Congenital fibrosis of extraocular muscles type 2 may result from the defective development of the

oculomotor (nIII), trochlear (nIV) and abducens (nVI) cranial nerve nuclei. Note=The disease is caused by

mutations affecting the gene represented in this entry

Selected diseases for PHOX2A (see all 22):
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congenital fibrosis of the extraocular muscles 2 paralytic squint phox2a-related congenital fibrosis of the extraocular muscles exotropia

hypotropia brown syndrome fibrosis of extraocular muscles, congenital, 1 congenital fibrosis of the extraocular muscles

mental retardation epilepsy congenital central hypoventilation syndrome amblyopia central hypoventilation syndrome

strabismus sudden infant death syndrome ophthalmoplegia neuroblastoma

mental retardation hypertension multiple myeloma myeloma

4 diseases from the University of Copenhagen DISEASES database for PHOX2A:

Exotropia Ophthalmoplegia Hypotropia Paralytic squint

PHOX2A for disorders About GeneDecksing

3 Novoseek inferred disease relationships for PHOX2A gene About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
cfeom2	95.3	12	12324876 (3), 11882252 (2), 14597037 (2)
cfeom	90.5	7	11882252 (3), 14597037 (1), 15747768 (1)
paralysis	22.4	9	16049556 (4), 18323871 (2)

GeneTests: PHOX2A
GeneReviews: PHOX2A
Genetic Association Database (GAD): PHOX2A
Human Genome Epidemiology (HuGE) Navigator: PHOX2A (1 document)

Export disorders for PHOX2A gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for PHOX2A gene, integrated from 10 sources (see all 61):
(articles sorted by number of sources associating them with PHOX2A)

Utopia: connect your pdf to the dynamic
world of online information

Homozygous mutations in ARIX(PHOX2A) result in congenital fibrosis of the extraocular muscles type 2. (PubMed id 11600883)^{1, 2, 3} Nakano M.... Engle E.C. (Nat. Genet. 2001)
Mapping of the ARIX homeodomain gene to mouse chromosome 7 and human chromosome 11q13. (PubMed id 8661014)^{1, 2, 3} Johnson K.R.... Lewis E.J. (Genomics 1996)
A novel PHOX2A/ARIX mutation in an Iranian family with congenital fibrosis of extraocular muscles type 2 (CFEOM2). (PubMed id 14597037)^{1, 4, 9} Yazdani A....Traboulsi E.I. (Am. J. Ophthalmol. 2003)
Molecular analysis of congenital central hypoventilation syndrome. (PubMed id 14566559)^{1, 2, 9} Sasaki A.... Hayasaka K. (Hum. Genet. 2003)
Sudden infant death syndrome: case-control frequency differences at genes pertinent to early autonomic nervous system embryologic development. (PubMed id 15240857)^{1, 4, 9} Weese-Mayer D.E....Marazita M.L. (Pediatr. Res. 2004)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S.... Malek J. (Genome Res. 2004)
ARIX and PHOX2B polymorphisms in patients with congenital superior oblique muscle palsy. (PubMed id 16049556)^{1, 9} Jiang Y....Yasuda T. (Acta Med. Okayama 2005)
The interaction between dHAND and Arix at the dopamine beta-hydroxylase promoter region is independent of direct dHAND binding to DNA. (PubMed id 14506227)^{1, 9} Rychlik J.L....Lewis E.J. (J. Biol. Chem. 2003)
Effects of transcription factors Phox2 on expression of norepinephrine transporter and dopamine beta-hydroxylase in SK-N-BE(2)C cells. (PubMed id 19573018)^{1, 9} Fan Y....Zhu M.Y. (J. Neurochem. 2009)
Phox2 and dHAND transcription factors select shared and unique target genes in the noradrenergic cell type. (PubMed id 16280598)^{1, 9} Rychlik J.L....Lewis E.J. (J. Mol. Neurosci. 2005)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 401	HGNC: 691	AceView: PHOX2A	Ensembl:ENSG00000165462	euGenes: HUgn401
ECgene: PHOX2A	H-InvDB: PHOX2A

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for PHOX2A	Pharmacogenomics, SNPs, Pathways
GeneReviews	http://www.ncbi.nlm.nih.gov/books/NBK1116/?term=PHOX2A[genesymbol]

Intellectual Property for PHOX2A gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for PHOX2A gene:
Search GeneIP for patents involving PHOX2A

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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