PHOX2B

PHOX2B
Identifiers
Aliases	PHOX2B, NBLST2, NBPhox, PMX2B, paired like homeobox 2b
External IDs	OMIM: 603851 MGI: 1100882 HomoloGene: 68371 GeneCards: 8929
Gene ontology Molecular function • sequence-specific DNA binding • RNA polymerase II regulatory region sequence-specific DNA binding • RNA polymerase II core promoter proximal region sequence-specific DNA binding • DNA binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Cellular component • nucleus • nuclear chromatin Biological process • negative regulation of cell proliferation • glial cell differentiation • respiratory system development • positive regulation of G2/M transition of mitotic cell cycle • medullary reticular formation development • transcription, DNA-templated • parasympathetic nervous system development • regulation of respiratory gaseous exchange by neurological system process • noradrenergic neuron development • cellular response to BMP stimulus • multicellular organism development • neural crest cell migration involved in autonomic nervous system development • hindbrain tangential cell migration • sympathetic nervous system development • skeletal muscle cell differentiation • enteric nervous system development • retrotrapezoid nucleus neuron differentiation • regulation of gene expression • positive regulation of neuron differentiation • brainstem development • inner ear development • negative regulation of cell cycle arrest • cell development • regulation of transcription, DNA-templated • sympathetic ganglion development • negative regulation of neuron differentiation • cell differentiation in hindbrain • autonomic nervous system development • efferent axon development in a lateral line nerve • neuron differentiation • neuron migration • dopaminergic neuron differentiation • noradrenergic neuron differentiation • positive regulation of transcription from RNA polymerase II promoter • transcription from RNA polymerase II promoter Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	8929	18935
Ensembl	ENSG00000109132	ENSMUSG00000012520
UniProt	Q99453	O35690
RefSeq (mRNA)	NM_003924	NM_008888
RefSeq (protein)	NP_003915.2	NP_032914.1
Location (UCSC)	Chr 4: 41.74 – 41.75 Mb	Chr 5: 67.09 – 67.1 Mb
PubMed search
Wikidata
View/Edit Human	View/Edit Mouse

Paired-like homeobox 2b (PHOX2B), also known as neuroblastoma Phox (NBPhox), is a protein that in humans is encoded by the PHOX2B gene located on chromosome 4.

It codes for a homeodomain transcription factor. It is expressed exclusively in the nervous system, in most neurons that control the viscera (cardiovascular, digestive and respiratory systems). It is also required for their differentiation.

Pathology

Mutations in human PHOX2B cause a rare disease of the visceral nervous system (dysautonomia): congenital central hypoventilation syndrome (associated with respiratory arrests during sleep and, occasionally, wakefulness), Hirschprung's disease (partial agenesis of the enteric nervous system), ROHHAD, and tumours of the sympathetic ganglia. In most people, Exon 3 of the gene contains a sequence of 20 polyalanine repeats. An increase in the number of repeats is associated with congenital central hypoventilation syndrome. There may also be other pathogenic mutations further along the gene.

Further reading

• Glas J, Seiderer J, Pasciuto G, et al. (2009). "rs224136 on chromosome 10q21.1 and variants in PHOX2B, NCF4, and FAM92B are not major genetic risk factors for susceptibility to Crohn's disease in the German population.". Am. J. Gastroenterol. 104 (3): 665–72. doi:10.1038/ajg.2008.65. PMID 19262523. 
• Gaultier C, Trang H, Dauger S, Gallego J (2005). "Pediatric disorders with autonomic dysfunction: what role for PHOX2B?". Pediatr. Res. 58 (1): 1–6. doi:10.1203/01.PDR.0000166755.29277.C4. PMID 15901893. 
• Liu CP, Li XG, Lou JT, et al. (2009). "Association analysis of the PHOX2B gene with Hirschsprung disease in the Han Chinese population of Southeastern China.". J. Pediatr. Surg. 44 (9): 1805–11. doi:10.1016/j.jpedsurg.2008.12.009. PMID 19735829. 
• Repetto GM, Corrales RJ, Abara SG, et al. (2009). "Later-onset congenital central hypoventilation syndrome due to a heterozygous 24-polyalanine repeat expansion mutation in the PHOX2B gene.". Acta Paediatr. 98 (1): 192–5. doi:10.1111/j.1651-2227.2008.01039.x. PMID 18798833. 
• Fan Y, Huang J, Kieran N, Zhu MY (2009). "Effects of transcription factors Phox2 on expression of norepinephrine transporter and dopamine beta-hydroxylase in SK-N-BE(2)C cells.". J. Neurochem. 110 (5): 1502–13. doi:10.1111/j.1471-4159.2009.06260.x. PMID 19573018. 
• McGaughey DM, Stine ZE, Huynh JL, et al. (2009). "Asymmetrical distribution of non-conserved regulatory sequences at PHOX2B is reflected at the ENCODE loci and illuminates a possible genome-wide trend.". BMC Genomics. 10: 8. doi:10.1186/1471-2164-10-8. PMC 2630312. PMID 19128492. 
• Jennings LJ, Yu M, Zhou L, et al. (2010). "Comparison of PHOX2B testing methods in the diagnosis of congenital central hypoventilation syndrome and mosaic carriers.". Diagn. Mol. Pathol. 19 (4): 224–31. doi:10.1097/PDM.0b013e3181eb92ff. PMID 21051998. 
• Tu E, Bagnall RD, Duflou J, et al. (2010). "Post-mortem pathologic and genetic studies in "dead in bed syndrome" cases in type 1 diabetes mellitus.". Hum. Pathol. 41 (3): 392–400. doi:10.1016/j.humpath.2009.08.020. PMID 20004937. 
• Janoueix-Lerosey I, Schleiermacher G, Delattre O (2010). "Molecular pathogenesis of peripheral neuroblastic tumors.". Oncogene. 29 (11): 1566–79. doi:10.1038/onc.2009.518. PMID 20101209. 
• Longo L, Borghini S, Schena F, et al. (2008). "PHOX2A and PHOX2B genes are highly co-expressed in human neuroblastoma.". Int. J. Oncol. 33 (5): 985–91. doi:10.3892/ijo_00000086. PMID 18949361. 
• Hammel M, Klein M, Trips T, et al. (2009). "Congenital Central Hypoventilation Syndrome due to PHOX2b gene defects: inheritance from asymptomatic parents.". Klin Padiatr. 221 (5): 286–9. doi:10.1055/s-0029-1220941. PMID 19707990. 
• Arai H, Otagiri T, Sasaki A, et al. (2010). "Polyalanine expansion of PHOX2B in congenital central hypoventilation syndrome: rs17884724:A>C is associated with 7-alanine expansion.". J. Hum. Genet. 55 (1): 4–7. doi:10.1038/jhg.2009.109. PMID 19881470. 
• Lee P, Su YN, Yu CJ, et al. (2009). "PHOX2B mutation-confirmed congenital central hypoventilation syndrome in a Chinese family: presentation from newborn to adulthood.". Chest. 135 (2): 537–44. doi:10.1378/chest.08-1664. PMID 19201717. 
• Wu HT, Su YN, Hung CC, et al. (2009). "Interaction between PHOX2B and CREBBP mediates synergistic activation: mechanistic implications of PHOX2B mutants.". Hum. Mutat. 30 (4): 655–60. doi:10.1002/humu.20929. PMID 19191321. 
• Trochet D, Mathieu Y, Pontual L, et al. (2009). "In Vitro studies of non poly alanine PHOX2B mutations argue against a loss-of-function mechanism for congenital central hypoventilation.". Hum. Mutat. 30 (2): E421–31. doi:10.1002/humu.20923. PMID 19058226. 
• Dubreuil V, Thoby-Brisson M, Rallu M, et al. (2009). "Defective respiratory rhythmogenesis and loss of central chemosensitivity in Phox2b mutants targeting retrotrapezoid nucleus neurons.". J. Neurosci. 29 (47): 14836–46. doi:10.1523/JNEUROSCI.2623-09.2009. PMID 19940179. 
• Serra A, Häberle B, König IR, et al. (2008). "Rare occurrence of PHOX2b mutations in sporadic neuroblastomas.". J. Pediatr. Hematol. Oncol. 30 (10): 728–32. doi:10.1097/MPH.0b013e3181772141. PMID 19011468. 
• Rudzinski E, Kapur RP (2010). "PHOX2B immunolocalization of the candidate human retrotrapezoid nucleus.". Pediatr. Dev. Pathol. 13 (4): 291–9. doi:10.2350/09-07-0682-OA.1. PMID 19888871. 
• Larkin EK, Patel SR, Goodloe RJ, et al. (2010). "A candidate gene study of obstructive sleep apnea in European Americans and African Americans.". Am. J. Respir. Crit. Care Med. 182 (7): 947–53. doi:10.1164/rccm.201002-0192OC. PMC 2970865. PMID 20538960. 
• Lee JJ, Essers JB, Kugathasan S, et al. (2010). "Association of linear growth impairment in pediatric Crohn's disease and a known height locus: a pilot study.". Ann. Hum. Genet. 74 (6): 489–97. doi:10.1111/j.1469-1809.2010.00606.x. PMC 2955808. PMID 20846217. 

External links

• GeneReviews/NCBI/NIH/UW entry on Congenital Central Hypoventilation Syndrome
• Phox2b protein at the US National Library of Medicine Medical Subject Headings (MeSH)