PHOX2B
Overview
PHOX2B (Paired-Like Homeobox 2B) is a homeodomain transcription factor critical for autonomic nervous system development and differentiation of noradrenergic neurons. It is also the gene mutated in congenital central hypoventilation syndrome. In neuroblastoma, PHOX2B marks the noradrenergic (NOR) tumor subpopulation and is associated with low-risk, favorable-outcome disease.
Alterations observed in the corpus
- PHOX2B is significantly over-expressed in noradrenergic (NOR) tumor clusters (nC5/nC7/nC8/nC9) of neuroblastoma relative to undifferentiated nC3 cells (FDR <0.01, Welch’s t-test) in a single-nuclei RNA-seq study of 11 tumors (Smart-Seq2). Co-expressed with PHOX2A, TH, DBH, PNMT, and ISL1 as part of the noradrenergic/adrenergic transcription panel. PMID:34493726
- Listed among germline candidate genes in high-risk neuroblastoma WES/WGS of 240 tumors (nbl_broad_2013); low overall somatic mutation burden (0.60/Mb) with germline predisposition variants enriched in ALK, CHEK2, PINK1, and BARD1 PMID:23334666
Cancer types (linked)
- NBL — defining marker of NOR tumor clusters enriched in low-risk and 4S neuroblastoma; NOR nC7/nC8 signatures associate with better overall survival in the 498-sample SEQC cohort (Bonferroni-corrected P <0.01). Also marks postnatal chromaffin cells in normal adrenal gland. PMID:34493726
Co-occurrence and mutual exclusivity
Therapeutic relevance
- PHOX2B expression marks NOR neuroblastoma with favorable prognosis; no direct targeted therapy is reported in the corpus.
Open questions
- The mechanism by which undifferentiated nC3 high-risk cells repress PHOX2B while activating MYCN/ALK programs is not resolved in this single-cell study. PMID:34493726
Sources
This page was processed by entity-page-writer on 2026-04-15. - PMID:23334666
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