PHOX2B paired like homeobox 2B [Homo sapiens (human)] - Gene

Summary

Official Symbol: PHOX2Bprovided by HGNC
Official Full Name: paired like homeobox 2Bprovided by HGNC
Primary source: HGNC:HGNC:9143
See related: Ensembl:ENSG00000109132 MIM:603851; AllianceGenome:HGNC:9143
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CCHS; PMX2B; NBLST2; NBPhox
Summary: The DNA-associated protein encoded by this gene is a member of the paired family of homeobox proteins localized to the nucleus. The protein functions as a transcription factor involved in the development of several major noradrenergic neuron populations and the determination of neurotransmitter phenotype. The gene product is linked to enhancement of second messenger-mediated activation of the dopamine beta-hydroylase, c-fos promoters and several enhancers, including cyclic amp-response element and serum-response element. Expansion of a 20 amino acid polyalanine tract in this protein by 5-13 aa has been associated with congenital central hypoventilation syndrome. [provided by RefSeq, Jul 2016]
Expression: Biased expression in adrenal (RPKM 4.8), small intestine (RPKM 0.5) and 3 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4p13

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (41744082..41748725, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (41717855..41722498, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (41746099..41750742, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

[Study of GCN repeats of PHOX2B gene among individuals from southwest China and diagnosis of two patients with Congenital central hypoventilation syndrome].
Title: [Study of GCN repeats of PHOX2B gene among individuals from southwest China and diagnosis of two patients with Congenital central hypoventilation syndrome].
Combined analysis of PHOX2B at two time points and its value for further risk stratification in high-risk neuroblastoma.
Title: Combined analysis of PHOX2B at two time points and its value for further risk stratification in high-risk neuroblastoma.
Spectrum of paired-like homeobox 2b immunoexpression in pediatric brain tumors with embryonal morphology.
Title: Spectrum of paired-like homeobox 2b immunoexpression in pediatric brain tumors with embryonal morphology.
The expression of PHOX2B in bone marrow and peripheral blood predicts adverse clinical outcome in non-high-risk neuroblastoma.
Title: The expression of PHOX2B in bone marrow and peripheral blood predicts adverse clinical outcome in non-high-risk neuroblastoma.
Reduced PHOX2B stability causes axonal growth impairment in motor neurons with TARDBP mutations.
Title: Reduced PHOX2B stability causes axonal growth impairment in motor neurons with TARDBP mutations.
Variable phenotypes in congenital central hypoventilation syndrome with PHOX2B nonpolyalanine repeat mutations.
Title: Variable phenotypes in congenital central hypoventilation syndrome with PHOX2B nonpolyalanine repeat mutations.
Adult-onset congenital central hypoventilation syndrome due to PHOX2B mutation.
Title: Adult-onset congenital central hypoventilation syndrome due to PHOX2B mutation.
Phox2b Immunohistochemical Staining in Detecting Enteric Neural Crest Cells in Hirschsprung Disease.
Title: Phox2b Immunohistochemical Staining in Detecting Enteric Neural Crest Cells in Hirschsprung Disease.
Paired-like homeobox gene (PHOX2B) nonpolyalanine repeat expansion mutations (NPARMs): genotype-phenotype correlation in congenital central hypoventilation syndrome (CCHS).
Title: Paired-like homeobox gene (PHOX2B) nonpolyalanine repeat expansion mutations (NPARMs): genotype-phenotype correlation in congenital central hypoventilation syndrome (CCHS).
NH2-terminal deletion of specific phosphorylation sites on PHOX2B disrupts the formation of enteric neurons in vivo.
Title: NH(2)-terminal deletion of specific phosphorylation sites on PHOX2B disrupts the formation of enteric neurons in vivo.

Submit: New GeneRIF Correction See all GeneRIFs (130)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease MedGen: C5562075 OMIM: 209880 GeneReviews: Congenital Central Hypoventilation Syndrome	not available
Neuroblastoma, susceptibility to, 2 MedGen: C2751682 OMIM: 613013 GeneReviews: Not available	not available

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2024-07-10) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2024-07-10) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-67926 (e-PCR)
- UniSTS:57636

MARC_17835-17836:1025010330:1 (e-PCR)
- UniSTS:268420

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in autonomic nervous system development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in brainstem development	IEP Inferred from Expression Pattern more info	PubMed
involved_in cell differentiation in hindbrain	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to BMP stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to carbon dioxide	IEA Inferred from Electronic Annotation more info
involved_in dopaminergic neuron differentiation	IC Inferred by Curator more info	PubMed
involved_in dopaminergic neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in efferent axon development in a lateral line nerve	ISS Inferred from Sequence or Structural Similarity more info
involved_in enteric nervous system development	IBA Inferred from Biological aspect of Ancestor more info
involved_in enteric nervous system development	IEP Inferred from Expression Pattern more info	PubMed
involved_in glial cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in hindbrain tangential cell migration	ISS Inferred from Sequence or Structural Similarity more info
involved_in inner ear development	ISS Inferred from Sequence or Structural Similarity more info
involved_in medullary reticular formation development	ISS Inferred from Sequence or Structural Similarity more info
involved_in membrane depolarization	IEA Inferred from Electronic Annotation more info
involved_in motor neuron migration	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of neuron differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of type B pancreatic cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in neural crest cell migration involved in autonomic nervous system development	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron migration	ISS Inferred from Sequence or Structural Similarity more info
involved_in noradrenergic neuron development	ISS Inferred from Sequence or Structural Similarity more info
involved_in noradrenergic neuron differentiation	IC Inferred by Curator more info	PubMed
involved_in noradrenergic neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in parasympathetic nervous system development	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of G2/M transition of mitotic cell cycle	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of neuron differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of respiratory gaseous exchange by nervous system process	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in respiratory system development	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to activity	IEA Inferred from Electronic Annotation more info
involved_in retrotrapezoid nucleus neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in skeletal muscle cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in sympathetic ganglion development	ISS Inferred from Sequence or Structural Similarity more info
involved_in sympathetic nervous system development	ISS Inferred from Sequence or Structural Similarity more info
involved_in type B pancreatic cell proliferation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in chromatin	IDA Inferred from Direct Assay more info	PubMed
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: paired mesoderm homeobox protein 2B

Names: PHOX2B homeodomain protein; neuroblastoma Phox; neuroblastoma paired-type homeobox protein; paired like homeobox2B; paired mesoderm homeobox 2b

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.