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Symbol PHOX2B contributors: mct - updated : 14-01-2011
HGNC name paired-like homeobox 2b
HGNC id 9143
Corresponding disease
CCHS3 congenital central hypoventilation syndrome 3
NBL4 neuroblastoma
Location 4p13      Physical location : 41.746.099 - 41.750.987
Synonym name
  • paired mesoderm homeobox 2b
  • neuroblastoma paired-type homeobox protein
  • neuroblastoma Phox
  • PHOX2B homeodomain protein
  • Synonym symbol(s) NBPHOX, PMXB, PMX2B, NBLST2
    TYPE functioning gene
    STRUCTURE 4.89 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    PWDMP 4p14 WD repeat membrane protein PWDMP RFC1 4p14-p13 replication factor C (activator 1) 1, 145kDa LOC152831 4p14 klotho beta like RPL9 4p13 ribosomal protein L9 LIAS 4p14 lipoic acid synthetase LOC391645 4 similar to WD repeat domain 5; Bmp2-induced gene UGDH 4p15.1 UDP-glucose dehydrogenase LOC201895 4p14 hypothetical protein LOC201895 HIP2 4p14 huntingtin interacting protein 2 LOC391646 4 similar to chromosome 6 open reading frame 46; Em:AF134726.1 KIAA0648 4p15.1-p11 similar to chromosome 6 open reading frame 46; Em:AF134726.1 PABPCP1 4p14 poly(A) binding protein, cytoplasmic, pseudogene 1 LOC391647 4 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) LOC344967 4p14 similar to cytosolic acyl coenzyme A thioester hydrolase N4BP2 4p14 Nedd4 binding protein 2 ARHH 4p13 ras homolog gene family, member H LOC339997 4p14 hypothetical LOC339997 CHRNA9 4p15.1-p14 cholinergic receptor, nicotinic, alpha polypeptide 9 FLJ20273 4p13-p12 RNA-binding protein FLJ14001 4p14 hypothetical protein FLJ14001 APBB2 4p15.1-p14 amyloid beta (A4) precursor protein-binding, family B, member 2 (Fe65-like) UCHL1 4p15.1-p14 ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) KIAA1102 4p13-p11 ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) PHOX2B 4p12 paired-like homeobox 2b FLJ10525 4p14 hypothetical protein FLJ10525 LOC285429 4p14 hypothetical protein LOC285429 SLC30A9 4p13-p12 solute carrier family 30 (zinc transporter), member 9 ATP1BL1 4p15-q13 ATPase, Na+/K+ transporting, beta polypeptide-like 1 LOC389206 4 hypothetical gene supported by AK125953 ATP8A1 4p14-p12 ATPase, aminophospholipid transporter (APLT), Class I, type 8A, member 1 LOC389207 4 similar to ENSANGP00000012385 LOC345302 4p13 similar to ribosomal protein S2; 40S ribosomal protein S2 PGBD3P4 4p14 piggyBac transposable element derived 3 pseudogene 4 KCTD8 4p13 potassium channel tetramerisation domain containing 8
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 3033 31.5 314 - 2008 18438890
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal gland    
    Nervousbrain   moderately
    Reproductivemale systemprostate  moderately
    Respiratorylung   moderately
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    cell lineage
    cell lines neuroblastoma cell lines
    at STAGE
    physiological period embryo
    Text expressed during neural development in central autonomic circuits and perpheral neural crest deerivatives
  • a paired-like homeodomain protein
  • two short and stable polyalanine repeats of 9 and 20n residues, respectively
  • five putative DNA sites that potentially bind homeodomain proteins, including PHOX2B itself
    intraspecies homolog to ARIX
  • paired homeobox family
  • CATEGORY transcription factor , signaling neurotransmitter
    SUBCELLULAR LOCALIZATION     intracellular
    text mutants carrying alanine expansion retained in the cytoplasm, both in widespread diffuse and in aggregated forms
    basic FUNCTION
  • involved in the signal-mediated expression in developing and mature catecholaminergic cells and neuradrenergic neurons and regulating ARIX during nervous system development
  • playing a major role in the patterning of the autonomous ventilation system and in the autonomic nervous system
  • transcription factors crucial in the development of neural-crest-derived cells, leading to ANS (autonomic nervous system) specific neuronal lineages
  • regulates its own expression by a transcriptional auto-regulatory mechanism
  • master regulator genes for peripheral SNS differentiation
  • drives ALK gene transcription by directly binding its promoter, which therefore represents a novel PHOX2B target)
  • recruited to different nodes in the genetic architecture of cell differentiation, while maintaining control over a visceral program
  • visceral sensory ganglia and the nucleus of the solitary tract all depend for their formation on the pan-visceral homeodomain transcription factor PHOX2B, also required in efferent neurons to the viscera
  • HOXB5 and PHOX2B, regulating enteric neural crest cells (ENCCs) proliferation, migration and differentiation could be risk factors for Hirschsprung disease (HSCR)
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS nervous system
    a component
    small molecule
  • interacting with PHOX2A (for its transcriptional regulation) and with DBH (role in the catecholamine biosynthesis)
  • needed for RET expression
  • able to bind the cell-specific element in the 5 prime regulatory region of the TLX2 gene, determining its transactivation in neuroblastoma cells (involved in the cascade leading to TLX2 transactivation and presumably in the intestinal neuronal differentiation)
  • interacting with MSX1 (downstream target of PHOX2B that activates the Delta-Notch pathway in neuroblastoma
  • HAND2 interacted with TCF3, and bound to the PHOX2B promoter region in sympathetic nervous system (SNS) differentiation
  • HAND2 can activate the SNS differentiation program by induction of SNS-related genes, including PHOX2B, ASCL1, DBH and TH
  • TRIM11 plays a critical role in the clearance of mutant PHOX2B through the proteasome
  • SOX10 regulation by PHOX2B is pivotal for the development and pathogenesis of the autonomic ganglia
  • TWIST1 interacts with the pro-neural factor SOX10 via its Twist-box domain and binds to the PHOX2B promoter to repress transcriptional activity
  • cell & other
    corresponding disease(s) CCHS3 , NBL4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    in familiar and sporadic neuroblastomas
    schizophrenia with strabismus
  • to neuroblastoma
  • to Parkinson disease (in association with ASCL1)
  • Variant & Polymorphism other variation in the 20-alanine homopolymer
    Candidate gene
    Therapy target
    murine b-/- death in utero