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

Summary

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Official Symbol: PHOX2Bprovided by HGNC
Official Full Name: paired-like homeobox 2bprovided by HGNC
Primary source: HGNC:9143
See related: Ensembl:ENSG00000109132; HPRD:09157; MIM:603851; Vega:OTTHUMG00000099379
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: 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. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 4p12

Sequence :: Chromosome: 4; NC_000004.11 (41746099..41750987, complement)

See PHOX2B in Epigenomics, MapViewer

Chromosome 4 - NC_000004.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

A new heterozygote mutation of exan 3 with duplication of 15 base pairs due to expansion of 5 alanines (genotype 20/25).
Title: [Late onset Ondine syndrome: literature review on a case report].
testing for PHOX2B mutation can assist iq the diagnosis of congenital central hypoventilation syndrome and in the prediction of disease progression.
Title: Congenital central hypoventilation syndrome with hirschsprung's disease due to PHOX2B gene mutation in a Turkish infant.
The findings for HOXB5 and PHOX2B provide supportive evidence that genes regulating ENCC proliferation, migration and differentiation could be risk factors for Hirschsprung's disease
Title: Hirschsprung's disease and variants in genes that regulate enteric neural crest cell proliferation, migration and differentiation.
Study shows that the E3 ubiquitin ligase TRIM11 plays a critical role in the clearance of mutant PHOX2B, which causes congenital central hypoventilation syndrome, through the proteasome.
Title: The E3 ubiquitin ligase TRIM11 mediates the degradation of congenital central hypoventilation syndrome-associated polyalanine-expanded PHOX2B.
report describes a family with recurrence of PHOX2B mutation-confirmed congenital central hypoventilation syndrome due to germline mosaicism
Title: Germline mosaicism of PHOX2B mutation accounts for familial recurrence of congenital central hypoventilation syndrome (CCHS).
Nearly 25% of congenital central hypoventilation syndrome patients carrying polyalanine expansion mutation inherit the PHOX2B mutation from parents with somatic mosaicism or constitutive mutation.
Title: Inheritance of polyalanine expansion mutation of PHOX2B in congenital central hypoventilation syndrome.
monoaminergic signaling pathways may play a central role in regulating amygdala activity.Candidate gene studies indicate that differences in amygdala activity may be caused by genetic variants within monoaminergic signaling pathways
Title: Associations between variants near a monoaminergic pathways gene (PHOX2B) and amygdala reactivity: a genome-wide functional imaging study.
PHOX2B, FGF12 and GAD2 genes are hypermethylated in colorectal neoplastic tissue
Title: Identification of novel DNA methylation markers in colorectal cancer using MIRA-based microarrays.
Patients with ARIX and/or PHOX2B polymorphisms had less hypoplastic superior oblique muscles.
Title: Phenotype-phenotype and genotype-phenotype correlations in patients with idiopathic superior oblique muscle palsy.
Review of the role of paired-like homeobox 2B (PHOX2B) genetic mutations in congenital central hypoventilation syndrome.
Title: Congenital central hypoventilation syndrome and the PHOX2B gene mutation.

Submit: New GeneRIF Correction See all (72)

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

Congenital central hypoventilation

MIM: 209880

Genetic Testing Registry

Summary from GeneReviews: Congenital Central Hypoventilation Syndrome

Congenital central hypoventilation syndrome (CCHS) is characterized by a classic presentation in newborns and a milder later-onset (LO-CCHS) presentation in toddlers, children, and adults. Classic CCHS presents in newborns as (1) apparent hypoventilation with monotonous respiratory rates and shallow breathing either during sleep only or while awake as well as asleep; (2) autonomic nervous system dysregulation (ANSD); and (3) in some individuals, altered development of neural crest-derived structures (i.e., Hirschsprung disease) and/or tumors of neural crest origin (neuroblastoma, ganglioneuroma, and ganglioneuroblastoma). Individuals with CCHS who have been diagnosed early and ventilated conservatively and consistently throughout childhood have reached the age of 20 to 30 years. LO-CCHS manifests as nocturnal alveolar hypoventilation and mild ANSD. Individuals with LO-CCHS who were not identified until age 20 years or older have reached the age of 30 to 55 years.

Diagnosis Testing

Diagnosis of CCHS is established based on (1) clinical findings of alveolar hypoventilation and ANSD in the absence of primary pulmonary, cardiac, or neuromuscular disease, or a causative brain stem lesion that can account for the entire phenotype; and (2) identification of a disease-causing mutation in PHOX2B. Molecular genetic testing of PHOX2B, the only gene in which mutations are known to cause CCHS, is available clinically.

Genetic Counseling

CCHS is inherited in an autosomal dominant manner. Most individuals with CCHS are heterozygous for a de novo PHOX2B mutation; some have an affected parent and 5%-10% have an asymptomatic parent who has mosaicism for a PHOX2B mutation. Each child of an individual with CCHS has a 50% chance of inheriting the PHOX2B mutation; the risk to the offspring of an individual with mosaicism is 50% or lower. Prenatal testing for pregnancies at increased risk is possible if the causative mutation has been identified in an affected family member.

References

PMID: 20301600

Neuroblastoma 2

MIM: 613013

Genetic Testing Registry

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description
BioGRID:114443	BioGRID:113164	UBC		BioGRID	PubMed	Affinity Capture-Western

Pathways from BioSystems

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Neural Crest Differentiation, organism-specific biosystem (from WikiPathways)
Neural Crest Differentiation, organism-specific biosystemGene regulatory network model of cranial neural crest cell (CNCC) development, adaped from PMID: 19575671. Most interactions in the model are proposed to regulate transcription of core factors involv...
SIDS Susceptibility Pathways, organism-specific biosystem (from WikiPathways)
SIDS Susceptibility Pathways, organism-specific biosystemIn this model, we provide an integrated view of Sudden Infant Death Syndrome (SIDS) at the level of implicated tissues, signaling networks and genetics. The purpose of this model is to serve as an ov...

General gene information

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Markers

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

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

Genotypes

See PHOX2B SNP Geneview Report
See PHOX2B SNP Genotype Report
See PHOX2B SNP Variation Viewer Report

Homology

Homologs of the PHOX2B gene: The PHOX2B gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
RNA polymerase II core promoter proximal region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
RNA polymerase II regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
sequence-specific DNA binding transcription factor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
autonomic nervous system development	IMP Inferred from Mutant Phenotype more info	PubMed
brainstem development	IEP Inferred from Expression Pattern more info	PubMed
cell differentiation in hindbrain	ISS Inferred from Sequence or Structural Similarity more info
cellular response to BMP stimulus	ISS Inferred from Sequence or Structural Similarity more info
dopaminergic neuron differentiation	IC Inferred by Curator more info	PubMed
dopaminergic neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
efferent axon development in a lateral line nerve	ISS Inferred from Sequence or Structural Similarity more info
enteric nervous system development	IEP Inferred from Expression Pattern more info	PubMed
glial cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
hindbrain tangential cell migration	ISS Inferred from Sequence or Structural Similarity more info
inner ear development	ISS Inferred from Sequence or Structural Similarity more info
medullary reticular formation development	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
negative regulation of neuron differentiation	IEA Inferred from Electronic Annotation more info
neural crest cell migration involved in autonomic nervous system development	ISS Inferred from Sequence or Structural Similarity more info
neuron migration	ISS Inferred from Sequence or Structural Similarity more info
noradrenergic neuron differentiation	IC Inferred by Curator more info	PubMed
noradrenergic neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
parasympathetic nervous system development	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of neuron differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of transcription from RNA polymerase II promoter	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription from RNA polymerase II promoter	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of respiratory gaseous exchange by neurological system process	ISS Inferred from Sequence or Structural Similarity more info
respiratory system development	ISS Inferred from Sequence or Structural Similarity more info
retrotrapezoid nucleus neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
sympathetic nervous system development	ISS Inferred from Sequence or Structural Similarity more info
transcription, DNA-dependent	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
nuclear chromatin	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: paired mesoderm homeobox protein 2B

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

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.

Genomic

NG_008243.1 RefSeqGene

Range

5001..9889

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_003924.3 → NP_003915.2 paired mesoderm homeobox protein 2B

Status: REVIEWED

Source sequence(s)

AC105389, AI266171, BC017199, D82344

Consensus CDS

CCDS3463.1

UniProtKB/Swiss-Prot

Q99453

Related

ENSP00000226382, OTTHUMP00000125223, ENST00000226382, OTTHUMT00000216832

Conserved Domains (1) summary

cd00086
Location:99 – 148
Blast Score: 183

homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000004.11 Reference GRCh37.p10 Primary Assembly

Range

41746099..41750987, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000136.1 Alternate HuRef

Range

41068497..41073385, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018915.1 Alternate CHM1_1.0

Range

41636163..41641051, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AB015671.1	BAA82670.1
genomic	ABBA01014273.1 (119555..124443)	None
genomic	AC105389.3 (101130..102070)	None
genomic	AF117979.1	AAD26698.1
genomic	AF414189.1	None
genomic	AMYH01014132.1 (527685..532573)	None
genomic	CH471069.1	EAW92989.1
mRNA	AI266171.1	None
mRNA	BC017199.2	AAH17199.1
mRNA	D82344.1	BAA11555.1