Homo sapiens gene PHOX2A, encoding paired-like homeobox 2a.
TABLE OF CONTENTS / OPEN CLOSE ALL PARAGRAPHS
SUMMARY back to top
RefSeq summary
[PHOX2A] 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].

RefSeq annotates one representative transcript (NM included in AceView variant.a), but Homo sapiens cDNA sequences in GenBank, dbEST, Trace and SRA, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 3 spliced variants.

AceView synopsis, each blue text links to tables and details
Expression: According to AceView, this gene is well expressed, 0.6 times the average gene in this release. The sequence of this gene is defined by 64 GenBank accessions from 63 cDNA clones, some from brain (seen 21 times), neuroblastoma cot 25-normalized (14), neuroblastoma, cell line (9), neuroblastoma (6), neuroblastoma cells (6), neuroblastoma cot 50-normalized (6), neuroblastoma cot 10-normalized (4) and 16 other tissues. We annotate structural defects or features in one cDNA clone.
Alternative mRNA variants and regulation: The gene contains 4 distinct gt-ag introns. Transcription produces 3 alternatively spliced mRNAs. There are 3 probable alternative promotors and 3 validated alternative polyadenylation sites (see the diagram). 1991 bp of this gene are antisense to spliced gene INPPL1, raising the possibility of regulated alternate expression.
Function: There are 26 articles specifically referring to this gene in PubMed. Functionally, the gene has been tested for association to diseases (OMIM: Fibrosis of extraocular muscles, congenital, 2; Other sources: Duane Retraction Syndrome; Epilepsy; Fibrosis; Mental Retardation; Neuroblastoma; Strabismus; Syndrome; Trochlear Nerve Diseases) and proposed to participate in processes (aging, locus ceruleus development, parasympathetic nervous system development, regulation of respiratory gaseous exchange, regulation of transcription, DNA-dependent, somatic motor neuron differentiation). Proteins are expected to have molecular functions (sequence-specific DNA binding, transcription factor activity) and to localize in nucleus. Putative protein interactors have been described (ATF6BANDTNXB, CREBBP, HAND2, JUN, PHOX2A, PRKACA).
Protein coding potential: The 3 spliced mRNAs putatively encode good proteins, altogether 3 different isoforms (1 complete, 2 COOH complete), some containing Homeobox domain [Pfam]. Finally proteins from this gene may be modulated by acetylation; phosphorylation, as detailed at PhosphoSite.

Please quote: AceView: a comprehensive cDNA-supported gene and transcripts annotation, Genome Biology 2006, 7(Suppl 1):S12.
Map on chromosome 11, links to other databases and other names
Map: This gene PHOX2A maps on chromosome 11, at 11q13.2 according to Entrez Gene. In AceView, it covers 7.46 kb, from 71956708 to 71949249 (NCBI 37, August 2010), on the reverse strand.
Links to: manual annotations from OMIM_602078, PhosphoSite, the SNP view, gene overviews from Entrez Gene 401, GeneCards, expression data from UniGene, molecular and other annotations from UCSC, or our GOLD analysis.
The previous AceView annotation is here.
Other names: The gene is also known as PHOX2A, ARIX, FEOM2, NCAM2, PMX2A, CFEOM2 or MGC52227, LOC401. It has been described as paired mesoderm homeobox protein 2A, arix homeodomain protein, ARIX1 homeodomain protein, aristaless homeobox homolog, aristaless homeobox protein homolog.
Closest AceView homologs in other species ?
The closest mouse gene, according to BlastP, is the AceView gene Phox2a (e=2 10-82).
The closest C.elegans genes, according to BlastP, are the AceView/WormGenes ceh-17 (e=2 10-28), alr-1 (e=6 10-25), which may contain interesting functional annotation.
The closest A.thaliana genes, according to BlastP, are the AceView genes HB-1 (e=4 10-07), AT4G17710 (e=10-06), HDG1 (e=2 10-05), HDG7 (e=3 10-05), which may contain interesting functional annotation
RNA_seq discoveries back to top
Expression/conservation in primates tissues evaluated by cross-mapping to human. back to top
PHOX2A Gene expression in 15 primates, 16 tissues, from the NHPRTR project in sFPKM BAB SkeletalMuscle WholeBlood CHP Kidney Liver Lung Spleen CMC CMM Cerebellum HUM Brain Colon Heart LymphNode Ovary Testis JMI BoneMarrow MLM OWL PTM RMC RMI Pituitary SQM Thymus MST SMY RTL 0.63 2.90 1.55 2.90 0.83 1.78 3.10 3.10 2.90 2.19 1.78 0.19 0.17 0.10 0.26 0.09 0.13 0.09 0.13 0.10 0.10 0.11 0.12 0.10 0.13 0.22 0.14 0.06 0.34 0.08 0.19 0.26 0.12 Expression quantiles None Weak 1 2 3 4 5 6 7 8 10 20 This gene All genes log2 distributions RNA-seq gene expression profile across 16 selected tissues from the Non-Human Primates Reference Transcriptome Resource (link to NHPRTR project).
- Primates: Apes (HUM: Human (Illumina BodyMap 2), CHP: Chimpanzee), Old World monkeys (PTM: Pig-Tailed Macaque, JMI Japanese Macaque, RMI Rhesus Macaque Indian, RMC Rhesus Macaque Chinese, CMM Cynomolgus Macaque Mauritian, CMC Cynomolgus Macaque Chinese, BAB Olive Baboon, SMY Sooty Mangabey); New World monkeys (MST common Marmoset, SQM Squirrel Monkey, OWL Owl Monkey); and Lemurs (MLM Mouse Lemur, RTL Ring-Tailed Lemur).
- The level for significantly expressed genes is color coded in 8 equal sized bins (light to dark green). Light gray is for weak not-accurately measured expression (2 to 8 reads above intergenic background); dark gray for no expression or no sequence conservation (0 read in gene). The plot to the right shows the distribution of measured expression values in all tissues for all genes (blue) and for this gene (green), in Magic index = log2(1000 sFPKM).
You may also examine the strand-specific genome coverage plots on the experimental AceView/Magic hub at UCSC, by tissue or by species. Tracks may be slow to load; please reload if some tracks come up yellow-greenish, and thanks to UCSC for the great work!.
Read more...
          Complete gene on genome diagram: back to top
Please choose between the zoomable GIF version., and the HTML5/SVG version.
This diagram shows in true scale the gene on the genome, the mRNAs and the cDNA clones.
Compact gene diagram back to top
Gene PHOX2A 5' 3' encoded on minus strand of chromosome 11 from 71,956,708 to 71,949,249 362001 329336 a [NM] 228 329336 b 1 c 1kb 0 388 bp exon 388 bp exon 2498 bp [gt-ag] intron 22 GenBank accessions 361979 RNA-seq supporting reads 145 UHR pooled cells 2 Brain 361819 Neuroblastoma 13 Other (also 6 Primates bodymap) 188 bp exon 903 bp [gt-ag] intron 32 GenBank accessions 329304 RNA-seq supporting reads 117 UHR pooled cells 1 Brain 329183 Neuroblastoma 3 Other (also 2 Primates bodymap) 1121 bp exon 37 accessions, NM_005169.3 some from brain (seen 17 times) neuroblastoma cot 25-normalized (10) neuroblastoma (6), neuroblastoma cells (6) neuroblastoma cot 50-normalized (6) capped 5' end, 3 accessions Validated 3' end, 7 accessions 1121 bp exon 85 bp exon 85 bp exon 4290 bp [gt-ag] intron 1 GenBank accession 227 RNA-seq supporting reads 227 Neuroblastoma 188 bp exon 903 bp [gt-ag] intron 32 GenBank accessions 329304 RNA-seq supporting reads 117 UHR pooled cells 1 Brain 329183 Neuroblastoma 3 Other (also 2 Primates bodymap) 1991 bp exon 24 accessions, some from brain (seen 4 times) neuroblastoma, cell line (4) leiomios (2), lymph (2) neuroblastoma cot 25-normalized (2) Validated 3' end, 1 accession 1991 bp exon 85 bp exon 85 bp exon 1188 bp [gt-ag] intron 1 GenBank accession 843 bp exon 1 accession from neuroblastoma cot 25-normalized 843 bp exon Alternative mRNAs are shown aligned from 5' to 3' on a virtual genome where introns have been shrunk to a minimal length. Exon size is proportional to length, intron height reflects the number of cDNAs supporting each intron, the small numbers show the support of the introns in deep sequencing (with details in mouse-over) . Introns of the same color are identical, of different colors are different. 'Good proteins' are pink, partial or not-good proteins are yellow, uORFs are green. 5' cap or3' poly A flags show completeness of the transcript.
Read more...
Sequences: click on the numbers to get the DNA back to top
mRNA variant mRNA matching the genome Best predicted protein 5' UTR 3' UTR Upstream sequence Transcription
unit
pre-mRNA
Downstream sequence
aAug10 1697 bp 284 aa 171 bp 671 bp 2kb including Promoter 5098 bp 1kb
bAug10 2264 bp 160 aa 1780 bp 2kb 7457 bp 1kb
cAug10 928 bp 78 aa 689 bp 2kb probably including promoter 2116 bp 1kb

Gene neighbors and Navigator on chromosome 11q13.2 back to top
FAM86C C I R DEFB108B R P RNF121 C R IL18BP D C I R P R R LRTOMT D C R P FOLR3 C R P FOLR1 D C I R P FOLR2 D C R P INPPL1 D C I R P R R R R R OR7E128P FOLR3P1 RPS12P20 G R G C R D C I R P NUMA1 C I R P C11orf59 C R P C11orf51 D C I R P PHOX2A G R C I R P CLPB C I R P PDE2A STARD10andARAP1 C 100kb 0 sworglaw, 17 accessions 2 variants FAM86C, 58 accessions 6 variants DEFB108B, 5 accessions 2 variants RNF121, 194 accessions 15 variants IL18BP, 138 accessions 10 variants blotubo, 61 accessions 2 variants cheeflobu, 3 accessions LRTOMT, 170 accessions 21 variants FOLR3, 45 accessions, 6 variants FOLR1, 182 accessions 5 variants FOLR2, 181 accessions 11 variants INPPL1, 568 accessions 17 variants feemoy, 5 accessions zawchor, 5 accessions 4 variants shyskeyby, 1 accession heyaro, 1 accession plumawby, 4 accessions pleemawby, 1 accession kohiro, 1 accession slawglarbu, 1 accession sleeglarbu, 1 accession vawmawby, 1 accession sloyglarbu, 2 accessions veymawby, 1 accession vormawby, 2 accessions smyglarbu, 1 accession seyfor, 2 accessions wumawby, 1 accession warmawby, 2 accessions wawmawby, 2 accessions weemawby, 1 accession wermawby, 3 accessions smeeglarbu, 3 accessions snupley, 1 accession plostoby, 1 accession smoyglarbu, 3 accessions zarmawby, 1 accession OR7E128P, 1 accession pleestoby, 1 accession snawglarbu, 1 accession chaferby, 5 accessions 3 variants spaglarbu, 1 accession spyglarbu, 1 accession chumawby, 1 accession plartobo, 5 accessions sparglarbu, 1 accession plorstoby, 1 accession cheemawby, 1 accession cheymawby, 1 accession chormawby, 2 accessions speeglarbu, 1 accession shymawby, 1 accession sufey, 4 accessions skorstoby, 1 accession sofey, 6 accessions rahuro, 1 accession stupley, 1 accession domoy, 7 accessions shormawby, 1 accession blymawby, 1 accession blumawby, 1 accession blarmawby, 1 accession glerkeyby, 6 accessions storpley, 2 accessions bloymawby, 1 accession barplor, 1 accession bawplor, 1 accession FOLR3P1, 1 accession flymawby, 2 accessions smeystoby, 1 accession smoystoby, 1 accession flormawby, 1 accession snustoby, 1 accession glamawby, 1 accession glomawby, 1 accession glarmawby, 6 accessions glawmawby, 1 accession glermawby, 1 accession gleymawby, 1 accession huyaro, 1 accession glormawby, 1 accession formoy, 8 accessions klumawby, 1 accession berglawbu, 1 accession borglawbu, 1 accession gumoy, 6 accessions kleymawby, 3 accessions klormawby, 1 accession goyplor, 1 accession boyglawbu, 1 accession plymawby, 1 accession RPS12P20, 1 accession plawmawby, 1 accession vomawby, 1 accession glawstoby, 1 accession smopley, 1 accession snapley, 2 accessions swyfoy, 1 accession klorstoby, 1 accession smuglarbu, 1 accession smawglarbu, 1 accession bawmoy, 7 accessions seekeyby, 1 accession hisomi, 3 accessions snopley, 1 accession smeyglarbu, 1 accession smorglarbu, 3 accessions worchor, 16 accessions plawstoby, 1 accession zumawby, 2 accessions zomawby, 7 accessions snaglarbu, 1 accession snyglarbu, 1 accession snarglarbu, 3 accessions husomi, 3 accessions zermawby, 3 accessions plotobo, 2 accessions beemoy, 1 accession zeymawby, 1 accession sneyglarbu, 1 accession snoyglarbu, 3 accessions zormawby, 2 accessions spupley, 1 accession spuglarbu, 1 accession stypley, 1 accession chomawby, 1 accession chawmawby, 1 accession chermawby, 1 accession skastoby, 1 accession spawglarbu, 1 accession skeystoby, 1 accession choymawby, 1 accession shamawby, 1 accession slastoby, 1 accession shoymawby, 1 accession blamawby, 2 accessions darmoy, 9 accessions sporglarbu, 1 accession starpley, 1 accession slystoby, 1 accession pleetobo, 1 accession bleemawby, 1 accession bleymawby, 23 accessions sawfey, 6 accessions starglarbu, 1 accession doymoy, 1 accession smustoby, 1 accession zochor, 7 accessions flomawby, 1 accession flarmawby, 1 accession flawmawby, 2 accessions steyglarbu, 3 accessions fleemawby, 2 accessions zarchor, 9 accessions cheyflobu, 3 accessions deeplor, 1 accession glymawby, 1 accession snostoby, 1 accession sneestoby, 3 accessions stoyglarbu, 1 accession gleemawby, 2 accessions hesomi, 2 accessions, 2 variants rihuro, 1 accession klamawby, 1 accession spostoby, 1 accession klomawby, 1 accession zerchor, 1 accession zeychor, 2 accessions derplor, 1 accession speystoby, 1 accession foymoy, 1 accession tawfey, 1 accession klarmawby, 1 accession bawglawbu, 1 accession geyplor, 1 accession gymoy, 2 accessions klermawby, 2 accessions chachor, 8 accessions teyfey, 3 accessions plamawby, 1 accession plomawby, 1 accession LOC285407, 14 accessions 5 variants LOC100133315, 60 accessions 14 variants NUMA1, 418 accessions 31 variants C11orf59, 563 accessions 8 variants C11orf51, 171 accessions 19 variants PHOX2A, 63 accessions 3 variants LOC220077, 1 accession fawmoy, 17 accessions CLPB, 408 accessions, 15 variants PDE2A, 384 accessions 35 variants STARD10andARAP1, 755 accessions 40 variants stukeyby, 1 accession ZOOM IN                D:disease,C:conserved,I:interactions,R:regulation,P:publications         Read more...
Annotated mRNA diagrams back to top
Bibliography:               26 articles in PubMed back to top
? Gene Summary Gene on genome mRNA:.a, .b, .c Alternative mRNAs features, proteins, introns, exons, sequences Expression Tissue Function, regulation, related genes DCI

To mine knowledge about the gene, please click the 'Gene Summary' or the 'Function, regulation, related genes ' tab at the top of the page. The 'Gene Summary' page includes all we learnt about the gene, functional annotations of neighboring genes, maps, links to other sites and the bibliography. The 'Function, regulation, related genes ' page includes Diseases (D), Pathways, GO annotations, conserved domains (C), interactions (I) reference into function, and pointers to all genes with the same functional annotation.
To compare alternative variants, their summarized annotations, predicted proteins, introns and exons, or to access any sequence, click the 'Alternative mRNAs features' tab. To see a specific mRNA variant diagram, sequence and annotation, click the variant name in the 'mRNA' tab. To examine expression data from all cDNAs clustered in this gene by AceView, click the 'Expression tissue'.

If you know more about this gene, or found errors, please share your knowledge. Thank you !