PHOX2B

PHOX2B
Identifiers
Aliases	PHOX2B, NBLST2, NBPhox, PMX2B, paired like homeobox 2b, CCHS
External IDs	OMIM: 603851; MGI: 1100882; HomoloGene: 68371; GeneCards: PHOX2B; OMA:PHOX2B - orthologs
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4p13 Start 41,744,082 bp[1] End 41,748,725 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5 C3.1|5 35.95 cM Start 67,251,742 bp[2] End 67,256,644 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in muscle layer of sigmoid colon buccal mucosa cell dorsal motor nucleus of vagus nerve inferior olivary nucleus rectum transverse colon appendix small intestine right adrenal gland duodenum Top expressed in migratory enteric neural crest cell external carotid artery pelvic ganglion enteric nervous system internal carotid artery adrenal gland facial motor nucleus female urethra medial vestibular nucleus male urethra More reference expression data BioGPS n/a
Gene ontology Molecular function sequence-specific DNA binding RNA polymerase II transcription regulatory region sequence-specific DNA binding RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus nucleoplasm Biological process negative regulation of cell population 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 nervous 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 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 by RNA polymerase II transcription by RNA polymerase II positive regulation of cold-induced thermogenesis nervous system development 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 NP_032914 Location (UCSC) Chr 4: 41.74 – 41.75 Mb Chr 5: 67.25 – 67.26 Mb PubMed search [3] [4]
Wikidata
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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.^[5]

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.

Essential for the differentiation and survival of sympathetic neurons and chromaffin cells, the transcription factor PHOX2B is highly specific for the peripheral autonomic nervous system. Neuroblasts are derived from sympathoadrenal lineage neural crest cells and therefore require and constitutively express PHOX2B. PHOX2B immunohistochemical staining, as a marker of neural crest derivation, has been shown to be sensitive and specific for undifferentiated neuroblastoma, enabling identification where other markers fail to recognize neuroblastoma among various different small round blue cell tumors of childhood.^[6][7][8][9]

The diagnostic utility of PHOX2B staining extends to later stages of differentiation. Its strength and specificity can detect the small foci of neuroblastic tumors metastatic to the bone marrow, an identification critical for determining disease staging. PHOX2B staining also overcomes frequent obstacles to neuroblastoma detection in post-treatment samples, which frequently exhibit dense fibrosis, prominent inflammatory infiltrates, and/or diffuse calcification.^[10]

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), Hirschsprung'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.

Organisations involved in researching Phox2B include those concerned with Congenitial Central Hypoventilation Syndrome. These include Keep Me Breathing^[11] based in the UK and The CCHS Network based in the USA. The CCHS Network held a scientific conference in September 2023, which covered significant research into Phox2B and CCHS with Keep Me Breathing presenting, too.^[12]

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

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