PHOX2A

Protein identityUniProt · HPA

UniProt accession

O14813

Gene

PHOX2A

Ensembl

ENSG00000165462

Chromosome

11

Canonical length

284 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm

OverviewNCBI Gene

The protein encoded by this gene contains a paired-like homeodomain most similar to that of the Drosophila aristaless gene product. The encoded protein plays a central role in development of the autonomic nervous system. It regulates the expression of tyrosine hydroxylase and dopamine beta-hydroxylase, two catecholaminergic biosynthetic enzymes essential for the differentiation and maintenance of the noradrenergic neurotransmitter phenotype. The encoded protein has also been shown to regulate transcription of the alpha3 nicotinic acetylcholine receptor gene. Mutations in this gene have been associated with autosomal recessive congenital fibrosis of the extraocular muscles. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

284 residues, UniProt reviewed canonical sequence.

>O14813|PHOX2A
     1  MDYSYLNSYD SCVAAMEASA YGDFGACSQP GGFQYSPLRP AFPAAGPPCP ALGSSNCALG
    61  ALRDHQPAPY SAVPYKFFPE PSGLHEKRKQ RRIRTTFTSA QLKELERVFA ETHYPDIYTR
   121  EELALKIDLT EARVQVWFQN RRAKFRKQER AASAKGAAGA AGAKKGEARC SSEDDDSKES
   181  TCSPTPDSTA SLPPPPAPGL ASPRLSPSPL PVALGSGPGP GPGPQPLKGA LWAGVAGGGG
   241  GGPGAGAAEL LKAWQPAESG PGPFSGVLSS FHRKPGPALK TNLF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PHOX2A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.64

Highest tissue expression

19 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PHOX2A.

Disease | AllUniProt

Conditions PHOX2A is implicated in, by any mechanism.

• Fibrosis of extraocular muscles, congenital, 2 (CFEOM2) MIM:602078

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 42 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Fibrosis of extraocular muscles, congenital, 2

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.8

gnomAD pLI

0.49

gnomAD missense Z

1.6

DepMap mean gene effect

-0.14

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• dopaminergic neuron differentiation
• midbrain development
• neuron development
• noradrenergic neuron differentiation
• oculomotor nerve formation
• positive regulation of transcription by RNA polymerase II
• regulation of respiratory gaseous exchange
• regulation of transcription by RNA polymerase II
• somatic motor neuron differentiation
• sympathetic nervous system development
• locus ceruleus development
• trochlear nerve formation

Molecular functions

• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity
• DNA-binding transcription factor activity, RNA polymerase II-specific
• RNA polymerase II transcription regulatory region sequence-specific DNA binding
• sequence-specific double-stranded DNA binding

Cellular components

• chromatin
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Homeodomain
• Homedomain-like superfamily
• Homeobox, conserved site
• Paired Homeobox Transcription Factors
• Homeodomain

KeywordsUniProt

• Activator
• DNA-binding
• Homeobox
• Nucleus
• Transcription
• Transcription regulation