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 ac... See more...

Aliases for PHOX2B Gene

Aliases for PHOX2B Gene

  • Paired Like Homeobox 2B 2 3 5
  • NBPhox 2 3 4
  • Paired Mesoderm Homeobox Protein 2B 3 4
  • Paired Mesoderm Homeobox 2b 2 3
  • PHOX2B Homeodomain Protein 3 4
  • Neuroblastoma Phox 3 4
  • PMX2B 3 4
  • Neuroblastoma Paired-Type Homeobox Protein 3
  • Paired Like Homeobox 2b 2
  • Paired-Like Homeobox 2B 4
  • Paired Like Homeobox2B 3
  • NBLST2 3
  • PHOX2B 5
  • CCHS 3

External Ids for PHOX2B Gene

Previous HGNC Symbols for PHOX2B Gene

  • PMX2B

Previous GeneCards Identifiers for PHOX2B Gene

  • GC04M042029
  • GC04M041596
  • GC04M041661
  • GC04M041587
  • GC04M041440
  • GC04M041068

Summaries for PHOX2B Gene

Entrez Gene Summary for PHOX2B Gene

  • 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]

GeneCards Summary for PHOX2B Gene

PHOX2B (Paired Like Homeobox 2B) is a Protein Coding gene. Diseases associated with PHOX2B include Central Hypoventilation Syndrome, Congenital and Neuroblastoma 2. Among its related pathways are Neural Crest Differentiation and Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways. Gene Ontology (GO) annotations related to this gene include RNA polymerase II proximal promoter sequence-specific DNA binding and RNA polymerase II regulatory region sequence-specific DNA binding. An important paralog of this gene is PHOX2A.

UniProtKB/Swiss-Prot Summary for PHOX2B Gene

  • Involved in the development of several major noradrenergic neuron populations, including the locus coeruleus. Transcription factor which could determine a neurotransmitter phenotype in vertebrates. Enhances second-messenger-mediated activation of the dopamine beta-hydrolase and c-fos promoters, and of several enhancers including cAMP-response element and serum-response element.

Gene Wiki entry for PHOX2B Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PHOX2B Gene

Genomics for PHOX2B Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for PHOX2B Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04J041746 Promoter/Enhancer 1.5 UCNEbase EPDnew Ensembl ENCODE 600.7 -0.3 -321 5.4 CTCF POLR2A EZH2 ZBTB44 FOXA1 ZSCAN5C OSR2 BCL11A SCRT1 WT1 ENSG00000249122 PHOX2B PHOX2B-AS1 TMEM33
GH04J041873 Enhancer 0.5 FANTOM5 30.8 -125.4 -125356 0.4 EZH2 POLR2A RCOR1 SMARCA4 CHD2 GATA2 PHOX2B ENSG00000249216 LIMCH1 ENSG00000249122 PHOX2B-AS1 LINC00682 HSALNG0034069 TMEM33
GH04J041709 Enhancer 1 Ensembl ENCODE 11.1 +38.5 38533 2 CREB1 ZNF629 PATZ1 ZNF501 ZNF600 ZNF561 ZBTB44 SP1 ZNF639 ZNF10 ENSG00000249216 lnc-PHOX2B-1 LIMCH1 PHOX2B PHOX2B-AS1 ENSG00000249122 RNU1-49P lnc-PHOX2B-4
GH04J041863 Enhancer 0.7 Ensembl 10.6 -115.1 -115130 0.9 ZNF692 ZSCAN4 ZNF501 ZNF341 RELB ZNF248 RUNX3 NBN WT1 ZFHX2 ENSG00000249122 PHOX2B SLC30A9 HSALNG0034069 LINC00682 TMEM33
GH04J041884 Enhancer 1 FANTOM5 ENCODE 7.4 -135.9 -135851 1 GATAD2A REST GABPA RXRB SP1 CEBPA FOXA2 CTCF ATF3 YY1 LINC00682 PHOX2B piR-45932-073 ENSG00000249771 TMEM33
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PHOX2B on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PHOX2B

Top Transcription factor binding sites by QIAGEN in the PHOX2B gene promoter:
  • CUTL1
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • E2F-5
  • SEF-1 (1)
  • SRY

Genomic Locations for PHOX2B Gene

Genomic Locations for PHOX2B Gene
chr4:41,744,082-41,748,725
(GRCh38/hg38)
Size:
4,644 bases
Orientation:
Minus strand
chr4:41,746,099-41,750,987
(GRCh37/hg19)
Size:
4,889 bases
Orientation:
Minus strand

Genomic View for PHOX2B Gene

Genes around PHOX2B on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PHOX2B Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PHOX2B Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PHOX2B Gene

Proteins for PHOX2B Gene

  • Protein details for PHOX2B Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99453-PHX2B_HUMAN
    Recommended name:
    Paired mesoderm homeobox protein 2B
    Protein Accession:
    Q99453
    Secondary Accessions:
    • Q6PJD9

    Protein attributes for PHOX2B Gene

    Size:
    314 amino acids
    Molecular mass:
    31621 Da
    Quaternary structure:
    • Interacts with TRIM11.

neXtProt entry for PHOX2B Gene

Post-translational modifications for PHOX2B Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PHOX2B Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for PHOX2B

No data available for DME Specific Peptides for PHOX2B Gene

Domains & Families for PHOX2B Gene

Gene Families for PHOX2B Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for PHOX2B Gene

Suggested Antigen Peptide Sequences for PHOX2B Gene

GenScript: Design optimal peptide antigens:
  • Paired-like homeobox 2B (PHX2B_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q99453

UniProtKB/Swiss-Prot:

PHX2B_HUMAN :
  • Belongs to the paired homeobox family.
Family:
  • Belongs to the paired homeobox family.
genes like me logo Genes that share domains with PHOX2B: view

Function for PHOX2B Gene

Molecular function for PHOX2B Gene

UniProtKB/Swiss-Prot Function:
Involved in the development of several major noradrenergic neuron populations, including the locus coeruleus. Transcription factor which could determine a neurotransmitter phenotype in vertebrates. Enhances second-messenger-mediated activation of the dopamine beta-hydrolase and c-fos promoters, and of several enhancers including cAMP-response element and serum-response element.

Phenotypes From GWAS Catalog for PHOX2B Gene

Gene Ontology (GO) - Molecular Function for PHOX2B Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IDA 16280598
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IDA 16144830
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISM 19274049
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IDA 16144830
GO:0003677 DNA binding IEA --
genes like me logo Genes that share ontologies with PHOX2B: view
genes like me logo Genes that share phenotypes with PHOX2B: view

Human Phenotype Ontology for PHOX2B Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for PHOX2B Gene

MGI Knock Outs for PHOX2B:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PHOX2B

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for PHOX2B Gene

Localization for PHOX2B Gene

Subcellular locations from UniProtKB/Swiss-Prot for PHOX2B Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PHOX2B gene
Compartment Confidence
nucleus 5
plasma membrane 2
extracellular 2
cytoskeleton 2
cytosol 2
mitochondrion 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for PHOX2B Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin IDA,ISA --
GO:0005634 nucleus IBA 21873635
GO:0005654 nucleoplasm IDA --
genes like me logo Genes that share ontologies with PHOX2B: view

Pathways & Interactions for PHOX2B Gene

genes like me logo Genes that share pathways with PHOX2B: view

Pathways by source for PHOX2B Gene

SIGNOR curated interactions for PHOX2B Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for PHOX2B Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001764 neuron migration IEA,ISS --
GO:0002087 regulation of respiratory gaseous exchange by neurological system process IEA,ISS --
GO:0003357 noradrenergic neuron differentiation IEA,ISS --
GO:0003358 noradrenergic neuron development IEA,ISS --
GO:0003360 brainstem development IEP 12640453
genes like me logo Genes that share ontologies with PHOX2B: view

Drugs & Compounds for PHOX2B Gene

(7) Drugs for PHOX2B Gene - From: ClinicalTrials, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Metronidazole Approved Pharma 725
cyclic amp Experimental Pharma 0
genes like me logo Genes that share compounds with PHOX2B: view

Transcripts for PHOX2B Gene

mRNA/cDNA for PHOX2B Gene

1 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PHOX2B

Alternative Splicing Database (ASD) splice patterns (SP) for PHOX2B Gene

No ASD Table

Relevant External Links for PHOX2B Gene

GeneLoc Exon Structure for
PHOX2B

Expression for PHOX2B Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PHOX2B Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PHOX2B Gene

This gene is overexpressed in Colon - Sigmoid (x20.5), Adrenal Gland (x8.9), Small Intestine - Terminal Ileum (x6.0), and Colon - Transverse (x5.8).

Protein differential expression in normal tissues from HIPED for PHOX2B Gene

This gene is overexpressed in Spleen (31.6), Esophagus (30.3), and Urinary Bladder (7.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for PHOX2B Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PHOX2B

SOURCE GeneReport for Unigene cluster for PHOX2B Gene:

Hs.87202

mRNA Expression by UniProt/SwissProt for PHOX2B Gene:

Q99453-PHX2B_HUMAN
Tissue specificity: Expressed in neuroblastoma, brain and adrenal gland.

Evidence on tissue expression from TISSUES for PHOX2B Gene

  • Nervous system(4.6)
  • Adrenal gland(2.5)

Phenotype-based relationships between genes and organs from Gene ORGANizer for PHOX2B Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • neck
  • outer ear
  • skull
Thorax:
  • chest wall
  • clavicle
  • diaphragm
  • heart
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • adrenal gland
  • intestine
  • kidney
  • large intestine
  • small intestine
Pelvis:
  • pelvis
  • rectum
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • peripheral nervous system
  • red blood cell
  • skin
  • spinal column
  • spinal cord
  • sweat gland
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with PHOX2B: view

No data available for Protein tissue co-expression partners for PHOX2B Gene

Orthologs for PHOX2B Gene

This gene was present in the common ancestor of animals.

Orthologs for PHOX2B Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PHOX2B 30 31
  • 99.36 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia PHOX2B 31
  • 99 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia PHOX2B 31
  • 99 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia PHOX2B 30 31
  • 92.89 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Phox2b 30 17 31
  • 91.3 (n)
OneToOne
Chicken
(Gallus gallus)
Aves PHOX2B 30 31
  • 89.07 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia PHOX2B 31
  • 94 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia phox2b 30
  • 82.69 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.32231 30
Zebrafish
(Danio rerio)
Actinopterygii phox2bb 30 31 31
  • 81.42 (n)
OneToMany
Fruit Fly
(Drosophila melanogaster)
Insecta PHDP 31
  • 32 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea ceh-17 31
  • 32 (a)
OneToMany
Species where no ortholog for PHOX2B was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rat (Rattus norvegicus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for PHOX2B Gene

ENSEMBL:
Gene Tree for PHOX2B (if available)
TreeFam:
Gene Tree for PHOX2B (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PHOX2B: view image

Paralogs for PHOX2B Gene

(13) SIMAP similar genes for PHOX2B Gene using alignment to 2 proteins:

  • PHX2B_HUMAN
  • H0YAD2_HUMAN
genes like me logo Genes that share paralogs with PHOX2B: view

Variants for PHOX2B Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PHOX2B Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
639360 Uncertain Significance: Congenital central hypoventilation 41,748,373(-) C/A MISSENSE_VARIANT
639964 Uncertain Significance: Congenital central hypoventilation 41,746,220(-) A/T MISSENSE_VARIANT
640336 Uncertain Significance: Congenital central hypoventilation; Hereditary cancer-predisposing syndrome 41,746,087(-) C/G MISSENSE_VARIANT
640568 Uncertain Significance: Congenital central hypoventilation 41,745,820(-) C/T MISSENSE_VARIANT
642737 Uncertain Significance: Congenital central hypoventilation 41,746,060(-) C/T MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for PHOX2B Gene

Structural Variations from Database of Genomic Variants (DGV) for PHOX2B Gene

Variant ID Type Subtype PubMed ID
esv32898 CNV gain 17666407

Variation tolerance for PHOX2B Gene

Residual Variation Intolerance Score: 34.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.86; 17.97% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PHOX2B Gene

Human Gene Mutation Database (HGMD)
PHOX2B
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PHOX2B

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PHOX2B Gene

Disorders for PHOX2B Gene

MalaCards: The human disease database

(26) MalaCards diseases for PHOX2B Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
central hypoventilation syndrome, congenital
  • cchs
neuroblastoma 2
  • neuroblastoma, susceptibility to, 2
hirschsprung disease ganglioneuroblastoma
  • neuroblastoma with hirschsprung disease
neuroblastoma
  • nb
sudden infant death syndrome
  • sids
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

PHX2B_HUMAN
  • Congenital central hypoventilation syndrome (CCHS) [MIM:209880]: Rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia. {ECO:0000269 PubMed:12640453, ECO:0000269 PubMed:14566559, ECO:0000269 PubMed:15657873}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Neuroblastoma 2 (NBLST2) [MIM:613013]: A common neoplasm of early childhood arising from embryonic cells that form the primitive neural crest and give rise to the adrenal medulla and the sympathetic nervous system. {ECO:0000305 PubMed:15024693}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Additional Disease Information for PHOX2B

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with PHOX2B: view

No data available for Genatlas for PHOX2B Gene

Publications for PHOX2B Gene

  1. PHOX2B genotype allows for prediction of tumor risk in congenital central hypoventilation syndrome. (PMID: 15657873) Trochet D … Amiel J (American journal of human genetics 2005) 3 4 23 41
  2. Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma. (PMID: 15024693) Trochet D … Amiel J (American journal of human genetics 2004) 3 4 23 41
  3. Association analysis of the PHOX2B gene with Hirschsprung disease in the Han Chinese population of Southeastern China. (PMID: 19735829) Liu CP … Li JC (Journal of pediatric surgery 2009) 3 23 41
  4. Unequal crossover recombination - population screening for PHOX2B gene polyalanine polymorphism using CE. (PMID: 17300129) Hung CC … Hsu SM (Electrophoresis 2007) 3 23 41
  5. PHOX2B analysis in non-syndromic neuroblastoma cases shows novel mutations and genotype-phenotype associations. (PMID: 16691592) McConville C … Rahman N (American journal of medical genetics. Part A 2006) 3 4 41

Products for PHOX2B Gene

Sources for PHOX2B Gene