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Paired-like homeobox 2b
Symbols PHOX2B ; NBLST2; NBPhox; PMX2B
External IDs OMIM603851 MGI1100882 HomoloGene68371 GeneCards: PHOX2B Gene
Species Human Mouse
Entrez 8929 18935
Ensembl ENSG00000109132 ENSMUSG00000012520
UniProt Q99453 O35690
RefSeq (mRNA) NM_003924 NM_008888
RefSeq (protein) NP_003915 NP_032914
Location (UCSC) Chr 4:
41.75 – 41.75 Mb
Chr 5:
67.09 – 67.1 Mb
PubMed search [1] [2]

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.[1]

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.


Mutations in human PHOX2B cause a rare disease of the visceral nervous system (or dysautonomia): Ondine's curse or Congenital Central Hypoventilation Syndrome (CCHS, associated with respiratory arrests during sleep and, occasionally, wakefulness), Hirschprung's disease (partial agenesis of the enteric nervous system) 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 are other non-polyalanine repeats that may also be involved, as well as other mutations of uncertain significance during gene sequencing.


Further reading[edit]

  • 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. 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. "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. 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. PMID 20846217. 

External links[edit]