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PHOX2B Gene(Protein Coding)

Paired Like Homeobox 2b

GCID:
GC04M041746
GIFtS:
51
Genes Participants
UDN Logo

Aliases for PHOX2B Gene

Aliases for PHOX2B Gene

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

Additional gene information for PHOX2B Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PHOX2B Gene

Genomics for PHOX2B Gene

Products:

  1. Regulatory Element

GeneHancer (GH) Regulatory Elements for PHOX2B Gene

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
GH04I041746 Promoter/Enhancer 1.6 UCNEbase EPDnew ENCODE 550.8 -0.1 -76 5.4 CTCF PKNOX1 SUZ12 FEZF1 POLR2A ZSCAN5C RCOR1 CHD2 EZH2 L3MBTL2 ENSG00000249122 PHOX2B LOC105374425
GH04I041873 Enhancer 0.5 FANTOM5 30.8 -125.1 -125111 0.4 POLR2A CTBP2 RCOR1 CHD2 EZH2 PHOX2B LOC105374421 LIMCH1 LOC105374425 ENSG00000249122 LINC00682 HMGB1P28
GH04I041709 Enhancer 0.9 ENCODE 11.1 +38.7 38707 1.8 ATF1 INSM2 KLF17 MZF1 ZNF76 FEZF1 ZNF2 BRCA1 ZNF335 ZNF213 LIMCH1 LOC105374425 PHOX2B ENSG00000249122 RNU1-49P LOC105374421 OR5M14P
GH04I041884 Enhancer 1 FANTOM5 ENCODE 7.4 -135.6 -135606 1 PKNOX1 FOXA2 RAD21 RARA YY1 RCOR1 MIXL1 RXRA REST NFIL3 LINC00682 PHOX2B ENSG00000249887 LOC105374426
GH04I041878 Enhancer 0.4 FANTOM5 18.2 -130.1 -130073 0.3 CTBP2 EZH2 PHOX2B LINC00682 HMGB1P28
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around PHOX2B on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the PHOX2B gene promoter:

Genomic Locations for PHOX2B Gene

Genomic Locations for PHOX2B Gene
chr4:41,744,082-41,748,970
(GRCh38/hg38)
Size:
4,889 bases
Orientation:
Minus strand
chr4:41,746,099-41,750,987
(GRCh37/hg19)

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 Structure • Gene Density

RefSeq DNA sequence for PHOX2B Gene

Proteins for PHOX2B Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • 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

Protein Expression for PHOX2B Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for PHOX2B Gene

No Post-translational modifications

Other Protein References for PHOX2B Gene

ENSEMBL proteins:
REFSEQ proteins:

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

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for PHOX2B Gene

GenScript: Design optimal peptide antigens:

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

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

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:0001077 transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding IDA 16144830
GO:0003677 DNA binding IEA --
GO:0043565 sequence-specific 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:

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

Nucleus.

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
cytosol 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PHOX2B Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin IDA 16280598
GO:0005634 nucleus IEA --
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 ISS,IEA --
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 ISS,IEA --
GO:0003360 brainstem development IEP 12640453
genes like me logo Genes that share ontologies with PHOX2B: view

Drugs & Compounds for PHOX2B Gene

Products:

  1. Drug

(6) Drugs for PHOX2B Gene - From: HMDB and Novoseek

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

Transcripts for PHOX2B Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for PHOX2B Gene

(1) REFSEQ mRNAs :
(3) Additional mRNA sequences :
(18) Selected AceView cDNA sequences:
(2) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for PHOX2B Gene

Paired-like homeobox 2b:
Representative Sequences:

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

No ASD Table

Relevant External Links for PHOX2B Gene

GeneLoc Exon Structure for
PHOX2B
ECgene alternative splicing isoforms for
PHOX2B

Expression for PHOX2B Gene

Products:

  1. Primer

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

mRNA expression in normal human tissues for PHOX2B Gene
mRNA expression by BioGPS for PHOX2B GenemRNA expression by GTEx 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, PaxDb, and MOPED for PHOX2B Gene



NURSA nuclear receptor signaling pathways regulating expression of PHOX2B Gene:

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(4.5)
  • Adrenal gland(2)

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
Organs:
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 33 34
  • 99.36 (n)
cow
(Bos Taurus)
 Mammalia PHOX2B 34
  • 99 (a)
 OneToOne
oppossum
(Monodelphis domestica)
 Mammalia PHOX2B 34
  • 99 (a)
 OneToOne
dog
(Canis familiaris)
 Mammalia PHOX2B 33 34
  • 92.89 (n)
mouse
(Mus musculus)
 Mammalia Phox2b 33 16 34
  • 91.3 (n)
chicken
(Gallus gallus)
 Aves PHOX2B 33 34
  • 89.07 (n)
lizard
(Anolis carolinensis)
 Reptilia PHOX2B 34
  • 94 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia phox2b 33
  • 82.69 (n)
African clawed frog
(Xenopus laevis)
 Amphibia Xl.32231 33
zebrafish
(Danio rerio)
 Actinopterygii phox2bb 33 34 34
  • 81.42 (n)
fruit fly
(Drosophila melanogaster)
 Insecta PHDP 34
  • 32 (a)
 OneToMany
worm
(Caenorhabditis elegans)
 Secernentea ceh-17 34
  • 32 (a)
 OneToMany
Species where no ortholog for PHOX2B was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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 squirt (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)

Paralogs for PHOX2B Gene

Paralogs for PHOX2B Gene

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

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

Variants for PHOX2B Gene

Sequence variations from dbSNP and Humsavar for PHOX2B Gene

SNP ID Clin Chr 04 pos Variation AA Info Type
rs104893855 risk-factor, uncertain-significance, Neuroblastoma 2, Congenital central hypoventilation 41,747,479(-) C/A coding_sequence_variant, missense_variant
rs104893856 risk-factor, Neuroblastoma 2 41,746,162(-) C/T coding_sequence_variant, missense_variant
rs1060501118 uncertain-significance, Congenital central hypoventilation 41,746,082(-) G/T coding_sequence_variant, missense_variant
rs1060501119 uncertain-significance, Congenital central hypoventilation 41,746,228(-) T/A coding_sequence_variant, missense_variant
rs1060501120 uncertain-significance, Congenital central hypoventilation 41,746,119(-) A/C coding_sequence_variant, missense_variant

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

(15) MalaCards diseases for PHOX2B Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, 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
  • neuroblastoma, susceptibility to
autonomic nervous system disease
  • autonomic nervous system disorder
- 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
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 22 44 58
  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 22 44 58
  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 22 44 58
  4. Unequal crossover recombination - population screening for PHOX2B gene polyalanine polymorphism using CE. (PMID: 17300129) Hung CC … Hsu SM (Electrophoresis 2007) 3 22 44 58
  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 44 58

Products for PHOX2B Gene

Sources for PHOX2B Gene

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