Pah phenylalanine hydroxylase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Pahprovided by MGI
Official Full Name: phenylalanine hydroxylaseprovided by MGI
Primary source: MGI:MGI:97473
See related: Ensembl:ENSMUSG00000020051 AllianceGenome:MGI:97473
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Summary: Enables phenylalanine 4-monooxygenase activity. Predicted to be involved in L-phenylalanine metabolic process; protein hydroxylation; and tyrosine biosynthetic process, by oxidation of phenylalanine. Predicted to act upstream of or within L-phenylalanine catabolic process. Is expressed in alimentary system; liver; and liver lobe. Used to study phenylketonuria. Human ortholog(s) of this gene implicated in intellectual disability and phenylketonuria. Orthologous to human PAH (phenylalanine hydroxylase). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in kidney adult (RPKM 253.9), liver adult (RPKM 186.5) and 3 other tissues See more
Orthologs: human all
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Genomic context

Location:: 10 C1; 10 43.64 cM

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	10	NC_000076.7 (87357657..87419999)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	10	NC_000076.6 (87521795..87584137)

Chromosome 10 - NC_000076.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A noncoding RNA modulator potentiates phenylalanine metabolism in mice.
Title: A noncoding RNA modulator potentiates phenylalanine metabolism in mice.
Mesenchymal stem cell energy deficit and oxidative stress contribute to osteopenia in the Pah(enu2) classical PKU mouse.
Title: Mesenchymal stem cell energy deficit and oxidative stress contribute to osteopenia in the Pah(enu2) classical PKU mouse.
A novel Pah-exon1 deleted murine model of phenylalanine hydroxylase (PAH) deficiency.
Title: A novel Pah-exon1 deleted murine model of phenylalanine hydroxylase (PAH) deficiency.
The Pah-R261Q mouse reveals oxidative stress associated with amyloid-like hepatic aggregation of mutant phenylalanine hydroxylase.
Title: The Pah-R261Q mouse reveals oxidative stress associated with amyloid-like hepatic aggregation of mutant phenylalanine hydroxylase.
In PAH deficient MSCs, expression of Col1A1 and Rankl are suppressed by hyperphenylalaninemia consistent with reduced bone formation and bone turnover. Osteopenia is intrinsic to phenylketonuria (PKU) pathology in untreated Pah(enu2) animals and our data suggests PHE toxicity participates by inhibiting mineralization in the course of MSC bone differentiation.
Title: A bone mineralization defect in the Pah(enu2) model of classical phenylketonuria involves compromised mesenchymal stem cell differentiation.
We observed mRNA correction rates up to 63%, restoration of phenylalanine hydroxylase (PAH) enzyme activity, and reversion of the light fur phenotype in Pah(enu2) mice. Our findings suggest that targeting genetic diseases in vivo using AAV-mediated delivery of base-editing agents is feasible, demonstrating potential for therapeutic application.
Title: Treatment of a metabolic liver disease by in vivo genome base editing in adult mice.
We demonstrate that kinetically instable and aggregation-prone variant Pah proteins trap BH4, shifting the pool of free BH4 towards bound BH4. Interference of PAH protein misfolding with metabolite-based control of l-phenylalanine turnover suggests a mechanistic link between perturbation of protein homeostasis and disturbed regulation of metabolic pathways.
Title: Secondary BH4 deficiency links protein homeostasis to regulation of phenylalanine metabolism.
We propose that CNS monoamine deficiency may be the cause of the partially reversible adverse behavioral effects associated with chronic HPA in Pah(enu2) mice, but that phenylalanine-reducing treatments initiated during adulthood are unable to correct the neuropathology and attendant cognitive deficits that develop during juvenile life in late-treated Pah(enu2/enu2) mice
Title: Blood phenylalanine reduction corrects CNS dopamine and serotonin deficiencies and partially improves behavioral performance in adult phenylketonuric mice.
we assessed DNA methylation patterns in brain tissues using methylated DNA immunoprecipitation and paired end sequencing in adult PAH(enu2) animals maintained under either continuous dietary Phe restriction or chronic hyperphenylalaninemia. Heterozygous PAH(enu2/WT) litter mates served as controls for normal Phe exposure
Title: DNA methylation in the pathophysiology of hyperphenylalaninemia in the PAH(enu2) mouse model of phenylketonuria.
These observations support the proposition that differences in phenylalanine hydroxylase activity underlie the variation in S-carboxymethyl-L-cysteine sulfoxidation and that no other enzyme is able to undertake this reaction.
Title: Phenylalanine monooxygenase and the sulfur oxygenation of S-carboxymethyl-L-cysteine in mice.

Submit: New GeneRIF Correction See all GeneRIFs (15)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (1) 1 citation
Chemically induced (ENU) (4) 1 citation
Not Applicable (1) 1 citation
Endonuclease-mediated (10) 1 citation

General gene information

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Markers

D10Mit118 (e-PCR), detects polymorphism
- UniSTS:126015

PAH (e-PCR), detects polymorphism
- UniSTS:266309

AW106920 (e-PCR)
- UniSTS:180096

D10Mit117 (e-PCR), detects polymorphism
- UniSTS:116376

PMC86965P2 (e-PCR)
- UniSTS:273568

D10Mit229 (e-PCR), detects polymorphism
- UniSTS:126132

RH127306 (e-PCR)
- UniSTS:210616

PAH (e-PCR), detects polymorphism
- UniSTS:144119

Pah (e-PCR), detects polymorphism
- UniSTS:144119

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables amino acid binding	ISO Inferred from Sequence Orthology more info
enables catalytic activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables iron ion binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables monooxygenase activity	IEA Inferred from Electronic Annotation more info
enables oxidoreductase activity	IEA Inferred from Electronic Annotation more info
enables oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen	IEA Inferred from Electronic Annotation more info
enables phenylalanine 4-monooxygenase activity	IBA Inferred from Biological aspect of Ancestor more info
enables phenylalanine 4-monooxygenase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables phenylalanine 4-monooxygenase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within L-phenylalanine catabolic process	IEA Inferred from Electronic Annotation more info
involved_in L-phenylalanine catabolic process	IEA Inferred from Electronic Annotation more info
involved_in L-phenylalanine metabolic process	ISO Inferred from Sequence Orthology more info
involved_in aromatic amino acid metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within metabolic process	IEA Inferred from Electronic Annotation more info
involved_in tyrosine biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in tyrosine biosynthetic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within tyrosine biosynthetic process, by oxidation of phenylalanine	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in tyrosine biosynthetic process, by oxidation of phenylalanine	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: phenylalanine-4-hydroxylase

Names: phe-4-monooxygenase

NP_032803.2

EC 1.14.16.1

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.

mRNA and Protein(s)

NM_008777.3 → NP_032803.2 phenylalanine-4-hydroxylase

See identical proteins and their annotated locations for NP_032803.2

Status: VALIDATED

Source sequence(s)

AA968324, AK145839, AK149519, BY074411

Consensus CDS

CCDS24102.1

UniProtKB/Swiss-Prot

P16331, Q91WV1

UniProtKB/TrEMBL

Q3UEH8

Related

ENSMUSP00000020241.8, ENSMUST00000020241.17

Conserved Domains (3) summary

TIGR01268
Location:20 → 452

Phe4hydrox_tetr; phenylalanine-4-hydroxylase, tetrameric form

cd04931
Location:21 → 110

ACT_PAH; ACT domain of the nonheme iron-dependent aromatic amino acid hydroxylase, phenylalanine hydroxylases (PAH)

pfam00351
Location:119 → 449

Biopterin_H; Biopterin-dependent aromatic amino acid hydroxylase