Affinage

PHOX2B

Paired mesoderm homeobox protein 2B · UniProt Q99453

Length
314 aa
Mass
31.6 kDa
Annotated
2026-04-28
100 papers in source corpus 47 papers cited in narrative 47 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PHOX2B is a paired-like homeodomain transcription factor that serves as a master regulator of autonomic nervous system development, controlling the specification, differentiation, and survival of sympathetic, parasympathetic, enteric, and visceral sensory neurons as well as branchial/visceral motor neurons in the hindbrain (PMID:10360575, PMID:10704382, PMID:10736201). It functions as a transcriptional activator that directly binds homeodomain recognition sites in the promoters of target genes including DBH, PHOX2A, TLX2, ALK, RET, and its own promoter (auto-regulation), coordinates cell cycle exit with neuronal subtype identity by inducing proneural genes and repressing non-neuronal fates, and cooperates with co-activators such as CREBBP/CBP and the proneural factor Mash1 to drive noradrenergic and cholinergic differentiation programs (PMID:16144830, PMID:16402914, PMID:20957039, PMID:11060244, PMID:19191321). In the postnatal brain, Phox2b-expressing glutamatergic neurons of the retrotrapezoid nucleus (RTN) and nucleus of the solitary tract (NTS) function as essential central CO₂/pH chemoreceptors whose activation drives respiratory rhythm via projections to the preBötzinger complex (PMID:18198276, PMID:19036978, PMID:25866925, PMID:30626698). Heterozygous PHOX2B mutations—polyalanine expansions and frameshifts—cause congenital central hypoventilation syndrome (CCHS) through distinct mechanisms including impaired DNA binding, defective nuclear import, cytoplasmic aggregation, disrupted auto-regulation, and dominant-negative or gain-of-function interference with wild-type protein activity (PMID:12640453, PMID:16249188, PMID:22922260, PMID:27129232).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1999 Medium

    Establishing that PHOX2B directly binds and cooperatively activates the DBH promoter via multimerization answered how a homeodomain factor controls noradrenergic gene expression at the molecular level.

    Evidence In vitro DNA binding, reporter/transactivation assays, and multimerization analysis in PC12h cells

    PMID:10395798

    Open questions at the time
    • No in vivo binding confirmation (ChIP)
    • Cooperative binding mechanism not structurally resolved
    • PKA synergy pathway not fully delineated
  2. 1999 High

    The Phox2b knockout demonstrated that a single transcription factor is required for the development of all autonomic ganglia and noradrenergic centers, establishing PHOX2B as a pan-autonomic master regulator rather than a lineage-restricted factor.

    Evidence Phox2b-null mouse with histological and gene expression analysis across sympathetic, parasympathetic, and enteric lineages

    PMID:10360575 PMID:10736201

    Open questions at the time
    • Direct transcriptional targets in each lineage not yet identified
    • Whether Phox2b acts cell-autonomously in all lineages was unresolved
  3. 2000 High

    Discovery that Phox2b is required for all branchial/visceral motor neurons and coordinates cell cycle exit with neuronal subtype specification expanded its role from the PNS to the CNS and identified it as a coupling factor between proliferation and differentiation.

    Evidence Phox2b-null mouse plus gain-of-function chick electroporation showing ectopic motor neuron generation

    PMID:10704382 PMID:11060244

    Open questions at the time
    • Cell cycle exit mechanism (direct target genes) unknown
    • Whether Phox2b directly represses cell cycle genes not tested
  4. 2001 Medium

    Demonstration that PHOX2B directly binds and transactivates the PHOX2A promoter placed the two paralogs in a hierarchical cascade, resolving the question of which acts upstream in autonomic specification.

    Evidence EMSA and cotransfection/luciferase reporter assay

    PMID:11549713

    Open questions at the time
    • No ChIP confirmation of in vivo binding at this stage
    • Whether PHOX2A feeds back on PHOX2B was not addressed
  5. 2003 High

    Identification of heterozygous PHOX2B polyalanine expansion mutations as the genetic cause of congenital central hypoventilation syndrome (CCHS) linked the transcription factor to human disease and implied dose-sensitive control of respiratory autonomic circuits.

    Evidence Mutation screening in CCHS patient cohort with embryonic expression analysis

    PMID:12640453

    Open questions at the time
    • Pathogenic mechanism of polyalanine expansions unknown
    • Which neuronal populations are affected in CCHS patients not determined
  6. 2003 High

    Phox2b heterozygous mice showed altered chemosensory responses and Phox2b was shown to control carotid body and epibranchial ganglion differentiation, extending its role to peripheral chemosensory organs critical for breathing control.

    Evidence Homozygous and heterozygous knockout mice with plethysmography and immunohistochemistry

    PMID:14627719

    Open questions at the time
    • Whether Phox2b directly regulates chemosensory transduction genes was unresolved
    • Central vs. peripheral contributions to respiratory phenotype not dissected
  7. 2004 High

    Mapping the upstream regulation of Phox2b itself—via Hox-Pbx-Prep ternary complexes on a conserved enhancer modulated by Nkx2.2—answered how anteroposterior and dorsoventral patterning signals converge to specify Phox2b expression domains in the hindbrain.

    Evidence Reporter assays with enhancer deletions/mutations, EMSA, and chick electroporation

    PMID:15289435

    Open questions at the time
    • Enhancers for non-hindbrain Phox2b expression domains not identified
    • In vivo validation of enhancer necessity (knockout of element) not performed
  8. 2005 High

    A series of studies resolved the pathogenic mechanisms of CCHS mutations: polyalanine expansions impair DNA binding, transactivation, and nuclear import in a length-dependent manner with cytoplasmic aggregation; frameshift mutations abolish transactivation with nucleolar sequestration; and PHOX2B auto-regulates its own promoter, which is disrupted by mutations.

    Evidence Transactivation assays, EMSA, immunofluorescence, gel filtration, ChIP on PHOX2B's own promoter

    PMID:15888479 PMID:16144830 PMID:16249188

    Open questions at the time
    • Whether aggregation is sufficient for pathogenesis vs. a byproduct was debated
    • In vivo confirmation in neuronal tissue not yet available
    • Auto-regulatory disruption not tested in animal models
  9. 2006 High

    Identification of TLX2 as a direct PHOX2B target (by ChIP, EMSA, and reporter assay) and demonstration that Phox2b is required for cholinergic gene expression in sympathetic ganglia expanded the catalog of direct transcriptional targets and confirmed dual noradrenergic/cholinergic specification.

    Evidence ChIP, EMSA, luciferase reporter, qRT-PCR in neuroblastoma cells; Phox2b-null mouse with in situ hybridization for ChAT/VAChT

    PMID:16402914 PMID:17017126

    Open questions at the time
    • Genome-wide binding profile not yet determined
    • Mechanism of cholinergic vs. noradrenergic fate choice not resolved
  10. 2008 High

    The PHOX2B(27Ala) knock-in mouse demonstrated that the CCHS mutation selectively eliminates Phox2b-expressing glutamatergic RTN neurons and abolishes CO₂ chemosensitivity, pinpointing the specific neuronal population whose loss causes central hypoventilation.

    Evidence Knock-in mouse with plethysmography, neuron counting, and CO₂ challenge

    PMID:18198276

    Open questions at the time
    • Whether RTN neuron loss is due to failed specification vs. degeneration was unclear
    • Contribution of other Phox2b+ populations (NTS, locus coeruleus) not dissected
  11. 2008 High

    Patch-clamp recordings established that Phox2b-expressing parafacial neurons are intrinsically CO₂/pH-sensitive (depolarize under TTX), glutamatergic, and NK1R-positive, defining the cellular identity and biophysical properties of the central chemoreceptor.

    Evidence Whole-cell patch-clamp in neonatal rat brainstem slices with TTX blockade and CO₂ challenge

    PMID:19036978

    Open questions at the time
    • Molecular mechanism of intrinsic pH sensing in these neurons unknown
    • Whether intrinsic sensitivity is the sole driver or requires synaptic input not resolved
  12. 2009 High

    Optogenetic activation and conditional genetic ablation of Phox2b+ RTN neurons demonstrated they are both necessary and sufficient for driving phrenic nerve activity and the central CO₂ chemoreflex, moving from correlative to causal evidence for their role in respiratory control.

    Evidence Lentiviral ChR2 optogenetics in rat with phrenic nerve recording; conditional Phox2b KO in mouse with embryonic electrophysiology and pH challenge

    PMID:19420248 PMID:19940179

    Open questions at the time
    • Downstream synaptic connectivity to preBötzinger complex not fully mapped
    • Role of non-RTN Phox2b+ neurons in respiratory drive unclear
  13. 2009 Medium

    Discovery that PHOX2B physically interacts with CREBBP/CBP and that CCHS mutations alter this interaction provided the first co-activator-based mechanism for how PHOX2B activates transcription and how mutations exert dominant-negative effects.

    Evidence Co-immunoprecipitation, domain mapping, cotransfection/luciferase reporter assays with mutant proteins

    PMID:19191321

    Open questions at the time
    • No structural resolution of the PHOX2B–CBP interface
    • Whether other coactivators or corepressors participate is unknown
    • Reciprocal Co-IP confirmed but not validated by independent methods
  14. 2010 High

    Identification of ALK as a direct PHOX2B transcriptional target in neuroblastoma cells, and demonstration that wild-type PHOX2B suppresses neuroblastoma proliferation while disease-associated mutants lose differentiation-promoting activity, connected PHOX2B's transcriptional program to oncogenesis.

    Evidence ChIP, siRNA knockdown, overexpression in neuroblastoma cell lines; proliferation and differentiation assays with mutant comparison

    PMID:17637745 PMID:20957039

    Open questions at the time
    • Whether PHOX2B is a bona fide tumor suppressor in vivo not demonstrated
    • Full set of neuroblastoma-relevant target genes unknown
  15. 2012 High

    Non-polyalanine PHOX2B mutations were shown to convert PHOX2B from a repressor to an activator of Sox10, causing sustained Sox10 expression and glial fate bias in enteric/sympathetic progenitors—providing a gain-of-function mechanism that explains the association of syndromic CCHS with Hirschsprung disease and neuroblastoma.

    Evidence Knock-in mouse with Sox10 enhancer reporter assays and embryonic progenitor analysis

    PMID:22922260

    Open questions at the time
    • Mechanism of switch from repression to activation not molecularly defined
    • Whether this applies to all NPARM mutations untested
  16. 2015 High

    Intersectional genetics demonstrated that the CO₂ chemoreflex requires specifically the Atoh1+Phox2b+ subset of RTN neurons and their glutamatergic transmission, refining the identity of the essential chemoreceptor population to a molecularly defined cell type.

    Evidence Dual Cre/Flpe intersectional mouse genetics, optogenetics, plethysmography, embryonic phrenic nerve recordings

    PMID:25866925

    Open questions at the time
    • Transcriptomic identity of Atoh1+Phox2b+ neurons at single-cell level not resolved
    • How Phox2b and Atoh1 interact at the regulatory level to specify these neurons unknown
  17. 2016 Medium

    Demonstration that PHOX2B forms homodimers and heterodimers with PHOX2A through its homeodomain, and that polyalanine expansions impair nuclear import through C-terminal interference rather than solely through aggregation, identified a distinct pathogenic mechanism for shorter CCHS expansions.

    Evidence Co-immunoprecipitation, mammalian two-hybrid, subcellular localization assays with truncation/expansion mutants

    PMID:27129232

    Open questions at the time
    • Structural basis of dimerization not resolved
    • In vivo relevance of heterodimerization for target gene regulation untested
    • Whether impaired import is the primary mechanism in neurons not confirmed
  18. 2019 Medium

    Chemogenetic and ablation studies of Phox2b-expressing NTS neurons revealed a second Phox2b+ respiratory circuit projecting to the preBötzinger complex, and pharmacological dissection showed serotonergic input modulates RTN chemosensitivity, revising the model from purely intrinsic pH sensing to a network-dependent mechanism.

    Evidence DREADD chemogenetics, neuron ablation, anterograde tracing in Phox2b-Cre mice; patch-clamp with 5-HT pharmacology in brain slices

    PMID:30626698 PMID:30866045

    Open questions at the time
    • Relative contributions of intrinsic pH sensing vs. serotonergic modulation to in vivo chemosensitivity not quantified
    • Full afferent/efferent connectome of Phox2b+ respiratory neurons not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the genome-wide direct target repertoire of PHOX2B across autonomic lineages, the structural basis of PHOX2B dimerization and co-activator recruitment, and how distinct PHOX2B mutation classes produce the full spectrum of CCHS-associated phenotypes including variable expressivity.
  • No genome-wide ChIP-seq in primary autonomic neurons published in the timeline
  • No crystal or cryo-EM structure of PHOX2B or its complexes
  • Genotype-phenotype correlation for rare PHOX2B variants mechanistically incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 11 GO:0003677 DNA binding 7
Localization
GO:0005634 nucleus 5
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-112316 Neuronal System 7 R-HSA-1266738 Developmental Biology 7 R-HSA-1643685 Disease 5
Partners
CREBBPHAND2MASH1PHOX2ATRIM11

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Phox2b is required for the development of all autonomic ganglia (sympathetic, parasympathetic, enteric) and three cranial sensory ganglia; in the enteric nervous system and sympathetic ganglia anlage, Phox2b is needed to maintain Mash1 expression and to induce expression of the GDNF receptor subunit Ret, as well as the noradrenaline biosynthesis enzymes dopamine-beta-hydroxylase and tyrosine hydroxylase. Genetic knockout mouse (loss-of-function), histology, gene expression analysis Nature High 10360575
2000 Phox2b is required for the formation of all branchial and visceral (but not somatic) motor neurons in the hindbrain; in its absence, motor neuron precursors die in the neuroepithelium or fail to switch on postmitotic markers, demonstrating Phox2b controls a novel cell-type-specific checkpoint in CNS neurogenesis. Genetic knockout mouse, histology, marker expression analysis Development High 10704382
2000 Phox2b is required for the differentiation of all central and peripheral noradrenergic neurons, including the locus coeruleus, making it a master regulator of the noradrenergic phenotype; Phox2b has a wider role than its paralog Phox2a and acts in a non-redundant partnership with Mash1. Genetic knockout mouse, gene expression analysis Molecular and cellular neurosciences High 10736201
2000 Phox2b coordinates neuronal cell cycle exit with subtype identity specification: loss-of-function reduces post-mitotic precursor numbers, while forced expression in chick spinal cord drives progenitors to become post-mitotic neurons with a motor neuronal phenotype (Islet1+ and cholinergic), acting as a transcriptional activator. Loss- and gain-of-function experiments (mouse KO and chick in ovo electroporation), marker expression Development High 11060244
2001 PHOX2B directly binds to a homeodomain recognition site in the 5' regulatory region of the human PHOX2A gene and transactivates its promoter, placing PHOX2B upstream of PHOX2A in the autonomic nervous system transcription factor cascade. Electrophoretic mobility shift assay (EMSA), cotransfection/luciferase reporter assay The Journal of neuroscience Medium 11549713
2002 Phox2b promotes generic neuronal differentiation by upregulating proneural genes (Ngn2, Mash1) and repressing inhibitors of neurogenesis (Hes5, Id2); it specifies branchio/visceromotor neuronal identity by repressing Pax6 and Olig2 and inducing Nkx6.1/Nkx6.2, acting as a transcriptional activator. Gain-of-function (chick electroporation), genetic analysis, gene expression profiling Development Medium 12399315
2003 Phox2b controls the differentiation of the carotid body chemosensor organ, the three epibranchial placode-derived visceral sensory ganglia (geniculate, petrosal, nodose), and is required for formation of the nucleus of the solitary tract; heterozygous Phox2b mutants show altered hypoxia/hypercapnia responses and reduced tyrosine hydroxylase expression in petrosal neurons. Homozygous and heterozygous knockout mice, plethysmography, immunohistochemistry, gene expression Development High 14627719
2003 PHOX2B directly binds to and transactivates the promoter of RGS4, and cooperates with Mash1 to induce RGS4 expression in vivo; Phox2b also controls gustducin (a G-protein alpha-subunit) expression in facial motor neurons, identifying components of G-protein signaling as part of the Phox2b-dependent neuronal differentiation program. In vivo KO mouse, chick spinal cord electroporation, gene expression analysis The Journal of neuroscience Medium 14627646
2003 PHOX2B is expressed in the human autonomic nervous system during embryonic development; heterozygous mutations (polyalanine expansions +5 to +9) are the primary cause of congenital central hypoventilation syndrome, establishing PHOX2B as essential for patterning the autonomic ventilation system. Human mutation screening, expression analysis in embryonic tissue Nature genetics High 12640453
2004 Integration of anteroposterior (Hoxb1/Hoxb2) and dorsoventral (Nkx2.2) signals converges on a conserved proximal Phox2b enhancer containing Pbx-Hox and Prep/Meis binding sites; Hox-Pbx-Prep ternary complex formation on this enhancer is required for rhombomere-restricted Phox2b expression in visceral motoneuron progenitors, and Nkx2.2 enhances Hox-mediated transactivation via derepression. Reporter assays with enhancer deletions/mutations, EMSA, chick in ovo electroporation Development High 15289435
2005 PHOX2B transactivation of target promoters (DBH, PHOX2A) is impaired by polyalanine expansions in a length-dependent manner; frameshift mutations abolish transactivation and DNA binding without causing cytoplasmic mislocalization, while longer polyalanine expansions (+9 and above) impair DNA binding and cause cytoplasmic aggregation with protein misfolding/multimerization in vitro. Transactivation assays, in vitro DNA binding assays, immunofluorescence, gel filtration of in vitro translated proteins Human molecular genetics High 16249188
2005 Polyalanine expansion and frameshift mutations in PHOX2B cause distinct pathogenetic mechanisms: polyalanine expansions reduce transactivation of DBH and PHOX2A in a length-dependent manner (with cytoplasmic retention for longer expansions), while frameshift mutations do not impair nuclear localization but instead cause sequestration in the nucleolar compartment. Transactivation reporter assays, immunofluorescence of transfected cells Human molecular genetics High 15888479
2005 PHOX2B auto-regulates its own expression by directly binding to four homeodomain recognition sites in its own promoter, as demonstrated by chromatin immunoprecipitation in vivo and EMSA in vitro; this auto-regulatory mechanism accounts for 65% of PHOX2B promoter activity in neuroblastoma cells. Chromatin immunoprecipitation (ChIP), EMSA, reporter/transactivation assays The Journal of biological chemistry High 16144830
2005 In Phox2b knockout mice, chromaffin cell maturation is arrested at an earlier stage than in Mash1 knockouts: cells lack TH, fail to form a medulla, and do not express dHand, Phox2a, c-ret, neurofilament, NST, or NCAM, demonstrating Phox2b regulates very early events in adrenal chromaffin cell differentiation upstream of Mash1. Knockout mouse (Phox2b knockin/lacZ), ultrastructural analysis, immunohistochemistry, gene expression Developmental biology High 15733675
2005 Phox2b heterozygous knockout mice display sleep-disordered breathing with increased apnea time and reduced ventilation during active sleep, partially modeling congenital central hypoventilation syndrome. Heterozygous KO mice, whole-body plethysmography, nuchal EMG sleep-wake staging American journal of respiratory and critical care medicine Medium 15860752
2006 PHOX2B directly binds to and transactivates the TLX2 gene 5' regulatory region in neuroblastoma cells, as confirmed by EMSA, transient transfections, and ChIP; forced PHOX2B overexpression upregulates endogenous TLX2 mRNA; CCHS-associated PHOX2B mutants show severely impaired TLX2 transactivation. EMSA, luciferase reporter assay, chromatin immunoprecipitation, quantitative RT-PCR The Biochemical journal High 16402914
2006 In the absence of Phox2b, expression of ChAT and VAChT from the cholinergic gene locus is absent from sympathetic ganglia, demonstrating that Phox2b is required for cholinergic neuron development in sympathetic ganglia. Phox2b knockout mouse, in situ hybridization for ChAT and VAChT mRNA Gene expression Medium 17017126
2006 Geldanamycin (an HSP90 inhibitor activating heat shock response) prevents formation of and induces clearance of cytoplasmic PHOX2B polyalanine aggregate proteins, rescues nuclear localization, and restores PHOX2B-mediated DBH promoter transactivation; clearance is mediated by proteasome and autophagy pathways. Transfection of PHOX2B-GFP fusion constructs in COS-7 cells, immunofluorescence, luciferase reporter assay, proteasome/autophagy inhibitor treatments The international journal of biochemistry & cell biology Medium 17045833
2004 Phox2b-induced generation of ectopic noradrenergic neurons in chick peripheral nerve involves induction of Cash1 (chick Mash1), and Phox2b coordinates generic and noradrenergic gene expression by recruiting Mash1/Cash1; conversely, Mash1 alone induces generic neuronal genes but requires additional autonomic codeterminants for full noradrenergic phenotype. Chick in vivo electroporation (gain-of-function), immunohistochemistry, gene expression Molecular and cellular neurosciences Medium 15033166
2008 Mice bearing the PHOX2B(27Ala) mutation (a human CCHS-causing mutation) specifically lack glutamatergic Phox2b-expressing neurons in the parafacial region, breathe irregularly, fail to respond to CO2, and die from central apnea; other breathing-relevant neuronal populations are anatomically normal, establishing parafacial RTN neurons as essential for CO2 chemosensation. Knock-in mouse model, histology, plethysmography, neuron counting, CO2 challenge Proceedings of the National Academy of Sciences High 18198276
2008 CO2-sensitive preinspiratory (Pre-I) neurons of the parafacial respiratory group (pFRG) in the neonatal rat express Phox2b, are depolarized by CO2 under TTX (i.e., exhibit intrinsic chemosensitivity), and are glutamatergic/NK1R-positive, establishing the identity and intrinsic properties of Phox2b+ parafacial neurons. Immunohistochemistry, electrophysiology (whole-cell patch-clamp in neonatal rat brainstem slices), TTX blockade, CO2 challenge The Journal of neuroscience High 19036978
2009 Phox2b interacts physically with CREBBP/CBP; CBP acts as a coactivator of PHOX2B to mediate synergistic activation of target genes; CCHS-associated PHOX2B mutants interact with different CBP domains than wild-type and show impaired synergistic activation, with some mutants exerting an interfering (dominant-negative) effect. Co-immunoprecipitation, domain-mapping experiments, cotransfection/luciferase reporter assays with mutant proteins Human mutation Medium 19191321
2009 Lentiviral expression of channelrhodopsin-2 under the Phox2b-responsive PRSx8 promoter in RTN neurons, followed by in vivo photostimulation, produces long-lasting activation of phrenic nerve activity; selective lesion of C1 adrenergic neurons abolishes the cardiovascular but not respiratory response, demonstrating non-catecholaminergic Phox2b+ RTN neurons function as central respiratory chemoreceptors. Lentiviral optogenetics (ChR2) in rat, in vivo phrenic nerve recording, selective C1 cell lesion The Journal of neuroscience High 19420248
2009 Conditional Phox2b mutations that deplete RTN neurons abolish rhythmic parafacial respiratory activity and reduce phrenic nerve discharge frequency in embryonic preparations; low-pH (CO2) challenge activates parafacial and phrenic activity in controls but not in mutants, providing genetic evidence that Phox2b-expressing RTN neurons drive respiratory rhythm and chemosensory input. Conditional knockout mouse, fetal brainstem-spinal cord preparations, phrenic/parafacial nerve electrophysiology, pH challenge The Journal of neuroscience High 19940179
2009 RTN neurons (Phox2b+, non-catecholaminergic, glutamatergic) are uniformly acid-activated in brain slices, contain VGLUT2 mRNA, and approximately 50% express preprogalanin; they receive both inhibitory and excitatory synaptic inputs and are in close contact with glial cells and capillary basement membranes, suggesting a role in CO2/H+ sensing. Patch-clamp electrophysiology in BAC eGFP-Phox2b transgenic mice, single-cell PCR, ultrastructural (electron microscopy) analysis The Journal of comparative neurology High 19711410
2008 Trim11 physically interacts with Phox2b (requiring the B30.2/SPRY domain of Trim11) and, when co-expressed with Phox2b, further increases DBH mRNA levels in primary avian neural crest stem cell cultures, suggesting Trim11 contributes to noradrenergic specification through Phox2b. Yeast two-hybrid, co-immunoprecipitation (protein-protein interaction), primary avian NCSC culture with forced expression, quantitative RT-PCR Biochemical and biophysical research communications Medium 18275850
2010 Selective inhibition of Phox2b-expressing neurons in the ventrolateral brainstem (RTN) using lentiviral-expressed allatostatin receptor abolishes CO2-evoked expiratory activity and reduces CO2-evoked inspiratory activity, demonstrating that Phox2b+ RTN neurons are essential for both chemoreceptor-driven expiration and inspiration. Lentiviral chemogenetic inhibition (allatostatin receptor) in rats, in vivo plethysmography, phrenic/abdominal nerve electrophysiology The Journal of neuroscience High 20844141
2010 Wild-type PHOX2B suppresses neuroblastoma cell proliferation and synergizes with retinoic acid to promote differentiation; neuroblastoma-associated PHOX2B mutants retain antiproliferative capacity but fail to promote differentiation or activate a known target gene, demonstrating disruption of transcription-dependent terminal differentiation. Forced overexpression in neuroblastoma cell lines, cell proliferation assay, differentiation assay, target gene (luciferase reporter) activation Oncogene Medium 17637745
2010 Phox2b-expressing neurons of the locus coeruleus (Phox2bLC) project to and activate preBötzinger complex neurons; chemogenetic stimulation of Phox2bLC neurons increases basal ventilation and ablation impairs the hypercapnic ventilatory response, establishing an LC-preBötzinger complex respiratory circuit. Cre-dependent DREADD (hM3Dq) in Phox2b-Cre mice, plethysmography, neuronal ablation, anterograde axon tracing Neuroscience bulletin Medium 32468398
2010 Neuroblastoma-associated Phox2b variants with homeodomain mutations lose the antiproliferative effect of wild-type Phox2b and, when endogenous Phox2b is reduced by siRNA, stimulate sympathetic neuron proliferation; this proliferative effect is blocked by Hand2 knockdown and rescued by Hand2 overexpression, implicating Hand2 in Phox2b-mediated proliferation control. siRNA knockdown, ectopic expression in primary embryonic sympathetic neurons, proliferation assay, Hand2 functional epistasis The Journal of neuroscience Medium 20089899
2010 PHOX2B directly binds to and drives transcription from the ALK gene promoter in neuroblastoma cells; siRNA knockdown of PHOX2B or PHOX2A downregulates ALK expression, and forced PHOX2B overexpression increases ALK protein, establishing ALK as a direct transcriptional target of PHOX2B. ChIP, siRNA knockdown, forced overexpression, qRT-PCR, Western blot in NB cell lines PloS one High 20957039
2011 Conditional targeting of the PHOX2B(27Ala) mutation to RTN neurons abolishes central CO2 chemosensitivity in neonates; however, these mutant mice survive and breathe normally beyond the first days after birth, with peripheral chemoreceptor O2 sensing compensating for lost CO2 response, demonstrating CO2 chemosensitivity is dispensable for early life breathing. Conditional knock-in mouse, plethysmography, hyperoxia challenge (to silence peripheral chemoreceptors), blood gas analysis The Journal of neuroscience High 21900566
2012 Nonpolyalanine repeat expansion mutations of PHOX2B (introduced into the mouse Phox2b locus) reduce transactivation of DBH in a dominant-negative fashion and convert PHOX2B's transcriptional effect on a Sox10 enhancer from repression to transactivation (gain-of-function), causing sustained Sox10 expression in enteric/sympathetic progenitors that biases them toward glial differentiation—mechanistically explaining HSCR and NB in syndromic CCHS. Knock-in mouse, reporter assay (DBH and Sox10 enhancer), co-transfection, embryonic progenitor analysis The Journal of clinical investigation High 22922260
2012 Polyalanine-expanded PHOX2B mutant proteins impair the PHOX2B auto-regulatory mechanism in a promoter-specific, dominant-negative fashion; co-expression of wild-type and mutant proteins in equimolar amounts reveals that cytoplasmic/nuclear aggregation is only a partial mechanism, as the shortest expansions impair transactivation without forming visible aggregates. Co-transfection luciferase reporter assays (PHOX2B, PHOX2A, DBH, TLX2 promoters), immunofluorescence, truncation mutant analysis Neurobiology of disease Medium 23103552
2013 Phox2b knockdown in zebrafish (modeling allelic deficiency) reduces sympathetic terminal differentiation markers (th, dbh); neuroblastoma-associated frameshift mutations (676delG, K155X) in the presence of endogenous Phox2b exert dominant-negative effects; Phox2b regulates its own expression (autoregulation) and ascl1, and phox2b deficiency uncouples this autoregulatory loop. Morpholino knockdown in zebrafish, overexpression of mutant constructs, in situ hybridization, gene expression analysis PLoS genetics Medium 23754957
2015 Intersectional genetic lesioning of RTN neurons co-expressing Atoh1 and Phox2b, or abrogation of glutamatergic transmission in these cells, abolishes the respiratory chemoreflex in behaving animals; photostimulation of these neurons entrains respiratory rhythm; this establishes Atoh1+Phox2b+ RTN neurons as a necessary component of the CO2 chemoreflex circuitry. Intersectional genetics (dual Cre/Flpe mouse lines), optogenetics (ChR2), whole-body plethysmography, embryonic phrenic nerve recordings eLife High 25866925
2016 PHOX2B forms homodimers and heterodimerizes with PHOX2A through homeodomain-mediated interactions; polyalanine-expanded PHOX2B retains partial heterodimerization with PHOX2A but the expanded C-terminus interferes with homeodomain-mediated nuclear import, providing a mechanism distinct from aggregation for loss of nuclear function. Co-immunoprecipitation, mammalian two-hybrid system, subcellular localization assays with truncation/expansion mutants The Journal of biological chemistry Medium 27129232
2017 Frameshift mutations in PHOX2B that result in different translational reading frames ('frame 2' vs 'frame 3') produce structurally and functionally distinct mutant proteins with different degrees of transcriptional dysfunction, correlating with isolated versus syndromic CCHS clinical presentation. In vitro transcription/translation, transactivation reporter assays, subcellular localization, clinical-molecular correlation Human mutation Medium 29098737
2017 Phox2b expression distinguishes oral cavity-projecting (taste) neurons from non-oral somatosensory neurons in the geniculate ganglion; all chorda tympani and greater superficial petrosal taste neurons express Phox2b, while auricular neurons do not, as shown by Phox2b-Cre-driven lineage tracing. Phox2b-Cre; tdTomato lineage tracing, nerve labeling, immunohistochemistry, chorda tympani transection The Journal of comparative neurology Medium 28856690
2017 PHOX2B polyalanine contractions (in-frame deletions in the polyalanine stretch) reduce transactivation of the RET promoter in vitro in a length-dependent manner, suggesting that contraction variants impair PHOX2B's ability to drive RET expression and may predispose to Hirschsprung disease. Luciferase reporter assay with RET promoter, co-transfection of PHOX2B polyalanine contraction variants Biochimica et biophysica acta. Molecular basis of disease Medium 28433712
2017 Nonsense mutations in exon 1 of PHOX2B escape nonsense-mediated decay and lead to translational reinitiation at a downstream AUG, producing N-terminally truncated proteins that localize to the nucleus and retain transactivation activity; this mechanism is distinct from polyalanine expansion mutations. In vitro translation, immunofluorescence (subcellular localization), luciferase reporter transactivation assay American journal of medical genetics. Part A Medium 28371199
2019 Chemogenetic (DREADD) stimulation of Phox2b-expressing NTS neurons increases baseline minute volume and synergizes with CO2 stimulation; genetic ablation of these neurons attenuates hypercapnic ventilatory responses; axons of Phox2b-NTS neurons project directly to the preBötzinger complex, establishing an NTS-to-respiratory CPG circuit. Cre-dependent hM3Dq DREADD in Phox2b-Cre mice, plethysmography, neuron ablation, anterograde axon tracing, c-Fos immunostaining The Journal of neuroscience Medium 30626698
2019 The CO2/pH response of Phox2b+ RTN neurons in brain slices is markedly reduced by 5-HT7 receptor antagonists and by inhibition of 5-HT synthesis, and enhanced by blocking 5-HT reuptake; RTN neurons are directly stimulated by endogenous and exogenous 5-HT, indicating that serotonergic input is a major mediator of RTN chemosensitivity rather than purely intrinsic pH sensing. Patch-clamp electrophysiology in brain slices and dissociated cultures, pharmacological manipulation of 5-HT signaling, in vivo plethysmography The Journal of physiology Medium 30866045
1999 NBPhox/PHOX2B binds to three sites in the dopamine beta-hydroxylase (DBH) gene promoter, forms DNA-independent multimers, and exhibits cooperative binding to the DB1 regulatory element; it enhances second messenger-mediated (cAMP/PKC) activation of the DBH promoter and other promoters (c-fos, CRE, AP-1, SRE), with transactivation synergized by PKA. In vitro DNA binding assay, reporter/transactivation assays in PC12h cells, multimerization analysis Genomics Medium 10395798
2000 Both Phox2a (Arix) and Phox2b (NBPhox) bind to three sites in the rat DBH promoter, form DNA-independent multimers, and exhibit cooperative binding to the DB1 element; both proteins synergistically increase DBH transcription in the presence of PKA; the N-terminal segment of Phox2a (50% identical to Phox2b) is essential for transcriptional regulatory activity, suggesting a similar transactivation mechanism. In vitro DNA binding assay, cotransfection/luciferase reporter assay, multimerization analysis DNA and cell biology Medium 11034547
2004 Haploinsufficiency for Phox2b in mice causes highly atrophic ciliary ganglion and dilated pupils; the ciliary ganglion is exquisitely sensitive to reduced Phox2b dosage compared to other autonomic ganglia; this and the intact DNA-binding domain of CCHS-associated polyalanine mutations suggest CCHS mutations are gain-of-function rather than pure loss-of-function. Heterozygous Phox2b knockout mouse, complementation test, histology Human molecular genetics Medium 15150159
2009 Transcription of Nkx2-1, PHOX2B, and Sox10 coordinately regulate RET promoter activity; PHOX2B has a responsive region in the RET promoter and acts cooperatively with Sox10 and Nkx2-1 (but not Pax3) to drive RET transcription in reporter assays. Dual-luciferase reporter assay, immunohistochemistry of human gut ganglions Journal of pediatric surgery Low 19853745

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives. Nature 695 10360575
2003 Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome. Nature genetics 639 12640453
2003 Idiopathic congenital central hypoventilation syndrome: analysis of genes pertinent to early autonomic nervous system embryologic development and identification of mutations in PHOX2b. American journal of medical genetics. Part A 283 14608649
2004 Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma. American journal of human genetics 254 15024693
2008 A human mutation in Phox2b causes lack of CO2 chemosensitivity, fatal central apnea, and specific loss of parafacial neurons. Proceedings of the National Academy of Sciences of the United States of America 246 18198276
2003 Phox2b controls the development of peripheral chemoreceptors and afferent visceral pathways. Development (Cambridge, England) 244 14627719
2000 Control of hindbrain motor neuron differentiation by the homeobox gene Phox2b. Development (Cambridge, England) 181 10704382
2009 Photostimulation of retrotrapezoid nucleus phox2b-expressing neurons in vivo produces long-lasting activation of breathing in rats. The Journal of neuroscience : the official journal of the Society for Neuroscience 180 19420248
2000 Specification of the central noradrenergic phenotype by the homeobox gene Phox2b. Molecular and cellular neurosciences 175 10736201
2006 Congenital central hypoventilation syndrome: PHOX2B mutations and phenotype. American journal of respiratory and critical care medicine 171 16888290
2008 CO2-sensitive preinspiratory neurons of the parafacial respiratory group express Phox2b in the neonatal rat. The Journal of neuroscience : the official journal of the Society for Neuroscience 132 19036978
2010 Essential role of Phox2b-expressing ventrolateral brainstem neurons in the chemosensory control of inspiration and expiration. The Journal of neuroscience : the official journal of the Society for Neuroscience 131 20844141
2011 Breathing without CO(2) chemosensitivity in conditional Phox2b mutants. The Journal of neuroscience : the official journal of the Society for Neuroscience 129 21900566
2009 Acid sensitivity and ultrastructure of the retrotrapezoid nucleus in Phox2b-EGFP transgenic mice. The Journal of comparative neurology 123 19711410
2007 Prevalence and functional consequence of PHOX2B mutations in neuroblastoma. Oncogene 118 17637745
2007 Central nervous system distribution of the transcription factor Phox2b in the adult rat. The Journal of comparative neurology 116 17559094
2005 Molecular consequences of PHOX2B missense, frameshift and alanine expansion mutations leading to autonomic dysfunction. Human molecular genetics 114 16249188
2009 Defective respiratory rhythmogenesis and loss of central chemosensitivity in Phox2b mutants targeting retrotrapezoid nucleus neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 108 19940179
2004 The Phox2B homeobox gene is mutated in sporadic neuroblastomas. Oncogene 102 15516980
2000 The Phox2b transcription factor coordinately regulates neuronal cell cycle exit and identity. Development (Cambridge, England) 92 11060244
2005 Distinct pathogenetic mechanisms for PHOX2B associated polyalanine expansions and frameshift mutations in congenital central hypoventilation syndrome. Human molecular genetics 88 15888479
2012 Autonomic neurocristopathy-associated mutations in PHOX2B dysregulate Sox10 expression. The Journal of clinical investigation 85 22922260
2008 PHOX2B is a novel and specific marker for minimal residual disease testing in neuroblastoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 83 18838715
2010 Photostimulation of Phox2b medullary neurons activates cardiorespiratory function in conscious rats. American journal of respiratory and critical care medicine 82 20622037
2015 The retrotrapezoid nucleus neurons expressing Atoh1 and Phox2b are essential for the respiratory response to CO₂. eLife 81 25866925
2008 Congenital central hypoventilation syndrome: PHOX2B genotype determines risk for sudden death. Pediatric pulmonology 76 18041756
2009 MYCN promotes the expansion of Phox2B-positive neuronal progenitors to drive neuroblastoma development. The American journal of pathology 73 19608868
2009 Phox2b, RTN/pFRG neurons and respiratory rhythmogenesis. Respiratory physiology & neurobiology 71 19712902
2008 The MSX1 homeobox transcription factor is a downstream target of PHOX2B and activates the Delta-Notch pathway in neuroblastoma. Experimental cell research 65 18201699
2005 The role of Phox2B in chromaffin cell development. Developmental biology 63 15733675
2005 Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma. Cancer letters 61 15949893
2003 Association study of PHOX2B as a candidate gene for Hirschsprung's disease. Gut 61 12631670
2004 Association between schizophrenia with ocular misalignment and polyalanine length variation in PMX2B. Human molecular genetics 60 14709596
2010 Congenital central hypoventilation syndrome and the PHOX2B gene: a model of respiratory and autonomic dysregulation. Respiratory physiology & neurobiology 58 20601214
2009 PHOX2B in respiratory control: lessons from congenital central hypoventilation syndrome and its mouse models. Respiratory physiology & neurobiology 54 19712905
2002 The role of Phox2b in synchronizing pan-neuronal and type-specific aspects of neurogenesis. Development (Cambridge, England) 54 12399315
2010 Neuroblastoma phox2b variants stimulate proliferation and dedifferentiation of immature sympathetic neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 52 20089899
2019 Causative and common PHOX2B variants define a broad phenotypic spectrum. Clinical genetics 51 31444792
2013 Distinct neuroblastoma-associated alterations of PHOX2B impair sympathetic neuronal differentiation in zebrafish models. PLoS genetics 50 23754957
2004 Integration of anteroposterior and dorsoventral regulation of Phox2b transcription in cranial motoneuron progenitors by homeodomain proteins. Development (Cambridge, England) 50 15289435
2003 Dynamic expression of RGS4 in the developing nervous system and regulation by the neural type-specific transcription factor Phox2b. The Journal of neuroscience : the official journal of the Society for Neuroscience 50 14627646
2005 Sleep-disordered breathing in newborn mice heterozygous for the transcription factor Phox2b. American journal of respiratory and critical care medicine 49 15860752
2009 Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3. Journal of pediatric surgery 48 19853745
2011 Variable human phenotype associated with novel deletions of the PHOX2B gene. Pediatric pulmonology 45 21830319
2006 PHOX2B analysis in non-syndromic neuroblastoma cases shows novel mutations and genotype-phenotype associations. American journal of medical genetics. Part A 45 16691592
2001 Sp proteins and Phox2b regulate the expression of the human Phox2a gene. The Journal of neuroscience : the official journal of the Society for Neuroscience 45 11549713
2000 Paired-like homeodomain proteins Phox2a/Arix and Phox2b/NBPhox have similar genetic organization and independently regulate dopamine beta-hydroxylase gene transcription. DNA and cell biology 45 11034547
2008 A Histone2BCerulean BAC transgene identifies differential expression of Phox2b in migrating enteric neural crest derivatives and enteric glia. Developmental dynamics : an official publication of the American Association of Anatomists 44 18351668
2013 A study of gata3 and phox2b expression in tumors of the autonomic nervous system. The American journal of surgical pathology 43 23715162
2012 PHOX2B immunolabeling: a novel tool for the diagnosis of undifferentiated neuroblastomas among childhood small round blue-cell tumors. The American journal of surgical pathology 42 22790854
2006 The TLX2 homeobox gene is a transcriptional target of PHOX2B in neural-crest-derived cells. The Biochemical journal 42 16402914
2003 PMX2B, a new candidate gene for Hirschsprung's disease. Clinical genetics 42 12919134
2019 Activation of Phox2b-Expressing Neurons in the Nucleus Tractus Solitarii Drives Breathing in Mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 40 30626698
2017 PHOX2B reliably distinguishes neuroblastoma among small round blue cell tumours. Histopathology 39 28640941
2008 Later-onset congenital central hypoventilation syndrome due to a heterozygous 24-polyalanine repeat expansion mutation in the PHOX2B gene. Acta paediatrica (Oslo, Norway : 1992) 39 18798833
2005 Facial phenotype in children and young adults with PHOX2B-determined congenital central hypoventilation syndrome: quantitative pattern of dysmorphology. Pediatric research 39 16327002
2010 PHOX2B-mediated regulation of ALK expression: in vitro identification of a functional relationship between two genes involved in neuroblastoma. PloS one 37 20957039
2019 Chemosensitivity of Phox2b-expressing retrotrapezoid neurons is mediated in part by input from 5-HT neurons. The Journal of physiology 36 30866045
2005 PHOX2B regulates its own expression by a transcriptional auto-regulatory mechanism. The Journal of biological chemistry 36 16144830
2012 Transcriptional dysregulation and impairment of PHOX2B auto-regulatory mechanism induced by polyalanine expansion mutations associated with congenital central hypoventilation syndrome. Neurobiology of disease 33 23103552
2017 Structural and functional differences in PHOX2B frameshift mutations underlie isolated or syndromic congenital central hypoventilation syndrome. Human mutation 32 29098737
2015 Diagnostic utility of PHOX2B in primary and treated neuroblastoma and in neuroblastoma metastatic to the bone marrow. Archives of pathology & laboratory medicine 31 25822764
2009 In Vitro studies of non poly alanine PHOX2B mutations argue against a loss-of-function mechanism for congenital central hypoventilation. Human mutation 31 19058226
2004 Interaction of Mash1 and Phox2b in sympathetic neuron development. Molecular and cellular neurosciences 31 15033166
2013 Contributions of PHOX2B in the pathogenesis of Hirschsprung disease. PloS one 29 23342068
2006 Cholinergic differentiation occurs early in mouse sympathetic neurons and requires Phox2b. Gene expression 29 17017126
2006 Geldanamycin promotes nuclear localisation and clearance of PHOX2B misfolded proteins containing polyalanine expansions. The international journal of biochemistry & cell biology 29 17045833
2005 Phox2B mutations and the Delta-Notch pathway in neuroblastoma. Cancer letters 29 16084642
2010 IL23R, NOD2/CARD15, ATG16L1 and PHOX2B polymorphisms in a group of patients with Crohn's disease and correlation with sub-phenotypes. International journal of molecular medicine 27 21206965
2017 Nonsense pathogenic variants in exon 1 of PHOX2B lead to translational reinitiation in congenital central hypoventilation syndrome. American journal of medical genetics. Part A 26 28371199
2011 In vitro drug treatments reduce the deleterious effects of aggregates containing polyAla expanded PHOX2B proteins. Neurobiology of disease 26 21964250
2004 Haploinsufficiency for Phox2b in mice causes dilated pupils and atrophy of the ciliary ganglion: mechanistic insights into human congenital central hypoventilation syndrome. Human molecular genetics 26 15150159
2017 Common PHOX2B poly-alanine contractions impair RET gene transcription, predisposing to Hirschsprung disease. Biochimica et biophysica acta. Molecular basis of disease 25 28433712
2014 PHOX2B polyalanine repeat length is associated with sudden infant death syndrome and unclassified sudden infant death in the Dutch population. International journal of legal medicine 25 24442913
2005 Pediatric disorders with autonomic dysfunction: what role for PHOX2B? Pediatric research 25 15901893
2017 The transcription factor Phox2b distinguishes between oral and non-oral sensory neurons in the geniculate ganglion. The Journal of comparative neurology 23 28856690
2017 Utility of Phox2b immunohistochemical stain in neural crest tumours and non-neural crest tumours in paediatric patients. Histopathology 23 28986989
2021 Paired-like homeobox gene (PHOX2B) nonpolyalanine repeat expansion mutations (NPARMs): genotype-phenotype correlation in congenital central hypoventilation syndrome (CCHS). Genetics in medicine : official journal of the American College of Medical Genetics 22 33958749
2008 Homozygous mutation of the PHOX2B gene in congenital central hypoventilation syndrome (Ondine's Curse). Human mutation 22 18407552
2005 Genetic association analyses of PHOX2B and ASCL1 in neuropsychiatric disorders: evidence for association of ASCL1 with Parkinson's disease. Human genetics 22 16021468
2018 Adult With PHOX2B Mutation and Late-Onset Congenital Central Hypoventilation Syndrome. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine 21 30518452
2008 PHOX2A and PHOX2B genes are highly co-expressed in human neuroblastoma. International journal of oncology 21 18949361
2007 Unequal crossover recombination - population screening for PHOX2B gene polyalanine polymorphism using CE. Electrophoresis 21 17300129
1999 Genomic structure and functional characterization of NBPhox (PMX2B), a homeodomain protein specific to catecholaminergic cells that is involved in second messenger-mediated transcriptional activation. Genomics 21 10395798
2014 Cytoarchitecture and CO(2) sensitivity of Phox2b-positive Parafacial neurons in the newborn rat medulla. Progress in brain research 20 24746043
2012 Relationship between the distribution of the paired-like homeobox gene (Phox2b) expressing cells and blood vessels in the parafacial region of the ventral medulla of neonatal rats. Neuroscience 20 22521817
2007 Transcriptional regulation of TLX2 and impaired intestinal innervation: possible role of the PHOX2A and PHOX2B genes. European journal of human genetics : EJHG 20 17505528
2012 Associations between variants near a monoaminergic pathways gene (PHOX2B) and amygdala reactivity: a genome-wide functional imaging study. Twin research and human genetics : the official journal of the International Society for Twin Studies 19 22856363
2007 Methylation-associated PHOX2B gene silencing is a rare event in human neuroblastoma. European journal of cancer (Oxford, England : 1990) 19 17765533
2001 Structural and functional characterization of the 5' upstream promoter of the human Phox2a gene: possible direct transactivation by transcription factor Phox2b. Journal of neurochemistry 19 11752063
2021 Disordered breathing in a Pitt-Hopkins syndrome model involves Phox2b-expressing parafacial neurons and aberrant Nav1.8 expression. Nature communications 18 34645823
2020 Respiratory Control by Phox2b-expressing Neurons in a Locus Coeruleus-preBötzinger Complex Circuit. Neuroscience bulletin 18 32468398
2016 Alanine Expansions Associated with Congenital Central Hypoventilation Syndrome Impair PHOX2B Homeodomain-mediated Dimerization and Nuclear Import. The Journal of biological chemistry 18 27129232
2014 Genetic analysis of PHOX2B in sudden unexpected death in epilepsy cases. Neurology 18 25085640
2008 Trim11 increases expression of dopamine beta-hydroxylase gene by interacting with Phox2b. Biochemical and biophysical research communications 18 18275850
2008 Rare occurrence of PHOX2b mutations in sporadic neuroblastomas. Journal of pediatric hematology/oncology 18 19011468
2014 RET and PHOX2B genetic polymorphisms and Hirschsprung's disease susceptibility: a meta-analysis. PloS one 17 24651702
2012 Inheritance of polyalanine expansion mutation of PHOX2B in congenital central hypoventilation syndrome. Journal of human genetics 17 22437207
2009 Interaction between PHOX2B and CREBBP mediates synergistic activation: mechanistic implications of PHOX2B mutants. Human mutation 17 19191321
2017 Variable phenotype in a novel mutation in PHOX2B. American journal of medical genetics. Part A 16 28422456