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Protein

Phenylalanine-4-hydroxylase

Gene

PAH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the hydroxylation of L-phenylalanine to L-tyrosine.2 Publications

Catalytic activityi

L-phenylalanine + tetrahydrobiopterin + O2 = L-tyrosine + 4a-hydroxytetrahydrobiopterin.2 Publications

Cofactori

Fe2+By similarity

Activity regulationi

N-terminal region of PAH is thought to contain allosteric binding sites for phenylalanine and to constitute an "inhibitory" domain that regulates the activity of a catalytic domain in the C-terminal portion of the molecule.2 Publications

Kineticsi

  1. KM=150 µM for L-phenylalanine1 Publication
  2. KM=154 µM for L-phenylalanine (at 25 degrees Celsius)1 Publication
  3. KM=30 µM for tetrahydrobiopterin (BH4)1 Publication
  4. KM=36 µM for tetrahydrobiopterin (BH4) (at 25 degrees Celsius)1 Publication
  1. Vmax=3500 nmol/min/mg enzyme towards L-phenylalanine (at 25 degrees Celsius)1 Publication
  2. Vmax=3600 nmol/min/mg enzyme towards tetrahydrobiopterin (BH4) (at 25 degrees Celsius)1 Publication
  3. Vmax=3640 nmol/min/mg enzyme towards L-phenylalanine (preincubated with L-Phe)1 Publication
  4. Vmax=1230 nmol/min/mg enzyme towards L-phenylalanine (preincubated with BH4)1 Publication

Temperature dependencei

Optimum temperature is 50 degrees Celsius.1 Publication

Pathwayi: L-phenylalanine degradation

This protein is involved in step 1 of the subpathway that synthesizes acetoacetate and fumarate from L-phenylalanine.
Proteins known to be involved in the 6 steps of the subpathway in this organism are:
  1. Phenylalanine-4-hydroxylase (PAH)
  2. Tyrosine aminotransferase (TAT)
  3. 4-hydroxyphenylpyruvate dioxygenase (HPD)
  4. Homogentisate 1,2-dioxygenase (HGD)
  5. Maleylacetoacetate isomerase (GSTZ1)
  6. Fumarylacetoacetase (FAH)
This subpathway is part of the pathway L-phenylalanine degradation, which is itself part of Amino-acid degradation.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes acetoacetate and fumarate from L-phenylalanine, the pathway L-phenylalanine degradation and in Amino-acid degradation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi285Iron; via tele nitrogenBy similarity1
Metal bindingi290Iron; via tele nitrogenBy similarity1
Metal bindingi330IronBy similarity1

GO - Molecular functioni

  • iron ion binding Source: InterPro
  • phenylalanine 4-monooxygenase activity Source: CACAO

GO - Biological processi

  • catecholamine biosynthetic process Source: BHF-UCL
  • cellular amino acid biosynthetic process Source: ProtInc
  • L-phenylalanine catabolic process Source: Reactome
  • neurotransmitter biosynthetic process Source: BHF-UCL

Keywordsi

Molecular functionAllosteric enzyme, Monooxygenase, Oxidoreductase
Biological processPhenylalanine catabolism
LigandIron, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS10374-MONOMER
BRENDAi1.14.16.1 2681
ReactomeiR-HSA-2160456 Phenylketonuria
R-HSA-71182 Phenylalanine and tyrosine catabolism
SABIO-RKiP00439
SIGNORiP00439
UniPathwayi
UPA00139;UER00337

Names & Taxonomyi

Protein namesi
Recommended name:
Phenylalanine-4-hydroxylase (EC:1.14.16.12 Publications)
Short name:
PAH
Alternative name(s):
Phe-4-monooxygenase
Gene namesi
Name:PAH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000171759.9
HGNCiHGNC:8582 PAH
MIMi612349 gene
neXtProtiNX_P00439

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Phenylketonuria (PKU)38 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal recessive inborn error of phenylalanine metabolism, due to severe phenylalanine hydroxylase deficiency. It is characterized by blood concentrations of phenylalanine persistently above 1200 mumol (normal concentration 100 mumol) which usually causes mental retardation (unless low phenylalanine diet is introduced early in life). They tend to have light pigmentation, rashes similar to eczema, epilepsy, extreme hyperactivity, psychotic states and an unpleasant 'mousy' odor.
See also OMIM:261600
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00086916S → P in PKU. Corresponds to variant dbSNP:rs62642946EnsemblClinVar.1
Natural variantiVAR_00087139Missing in PKU; haplotypes 9,21. 2 Publications1
Natural variantiVAR_00087240S → L in PKU. 1 PublicationCorresponds to variant dbSNP:rs62642938EnsemblClinVar.1
Natural variantiVAR_00087341L → F in PKU. Corresponds to variant dbSNP:rs62642928EnsemblClinVar.1
Natural variantiVAR_00924041L → P in PKU; mild. Corresponds to variant dbSNP:rs62642916EnsemblClinVar.1
Natural variantiVAR_00087442K → I in PKU; haplotype 21. Corresponds to variant dbSNP:rs62635346EnsemblClinVar.1
Natural variantiVAR_06799445V → A in PKU. 1 Publication1
Natural variantiVAR_00087546G → S in PKU; haplotype 5; significantly reduces phenylalanine binding. 1 PublicationCorresponds to variant dbSNP:rs74603784EnsemblClinVar.1
Natural variantiVAR_00087748L → S in PKU; mild; haplotypes 3,4. 5 PublicationsCorresponds to variant dbSNP:rs5030841EnsemblClinVar.1
Natural variantiVAR_00087853R → H in PKU. 1 PublicationCorresponds to variant dbSNP:rs118092776EnsemblClinVar.1
Natural variantiVAR_00088056E → D in PKU; haplotype 10. Corresponds to variant dbSNP:rs199475567EnsemblClinVar.1
Natural variantiVAR_06799561N → D in PKU. 1 PublicationCorresponds to variant dbSNP:rs199475651EnsemblClinVar.1
Natural variantiVAR_06799662L → P in PKU. 1 Publication1
Natural variantiVAR_00088163 – 64TH → PN in PKU; haplotype 1; abolishes phenylalanine binding. 2
Natural variantiVAR_00088265I → N in PKU. 1 PublicationCorresponds to variant dbSNP:rs75193786EnsemblClinVar.1
Natural variantiVAR_06799765I → S in PKU; results in disturbed oligomerization; results in loss of substrate activation. 2 PublicationsCorresponds to variant dbSNP:rs75193786EnsemblClinVar.1
Natural variantiVAR_00088365I → T in PKU; haplotypes 1,5,9,21,B; abolishes phenylalanine binding. 3 PublicationsCorresponds to variant dbSNP:rs75193786EnsemblClinVar.1
Natural variantiVAR_00088467S → P in PKU; haplotype 4. Corresponds to variant dbSNP:rs5030842EnsemblClinVar.1
Natural variantiVAR_00088568R → S in PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs76394784EnsemblClinVar.1
Natural variantiVAR_00088676E → A in PKU. Corresponds to variant dbSNP:rs62507347EnsemblClinVar.1
Natural variantiVAR_00088784D → Y in PKU; haplotype 4. Corresponds to variant dbSNP:rs62514902EnsemblClinVar.1
Natural variantiVAR_00088992T → I in PKU. Corresponds to variant dbSNP:rs62514903EnsemblClinVar.1
Natural variantiVAR_00089094Missing in PKU; mild; haplotype 2. 1 Publication1
Natural variantiVAR_000892104A → D in PKU; mild; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs62642929EnsemblClinVar.1
Natural variantiVAR_000893124T → I in PKU; haplotype 28. Corresponds to variant dbSNP:rs199475571EnsemblClinVar.1
Natural variantiVAR_000894129D → Y in PKU. Corresponds to variant dbSNP:rs199475606EnsemblClinVar.1
Natural variantiVAR_000895143D → G in PKU; haplotype 11. 1 PublicationCorresponds to variant dbSNP:rs199475572EnsemblClinVar.1
Natural variantiVAR_011566145D → V in PKU. Corresponds to variant dbSNP:rs140175796EnsemblClinVar.1
Natural variantiVAR_000896146H → Y in PKU. Corresponds to variant dbSNP:rs199475599EnsemblClinVar.1
Natural variantiVAR_000897148G → S in PKU; haplotypes 1,2,7. Corresponds to variant dbSNP:rs80297647EnsemblClinVar.1
Natural variantiVAR_000898151D → H in PKU; haplotypes 1,8. Corresponds to variant dbSNP:rs199475597EnsemblClinVar.1
Natural variantiVAR_000899154Y → N in PKU. Corresponds to variant dbSNP:rs199475587EnsemblClinVar.1
Natural variantiVAR_009242155R → P in PKU. Corresponds to variant dbSNP:rs199475663EnsemblClinVar.1
Natural variantiVAR_000900157R → N in PKU; severe; 5% activity; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_068000157R → S in PKU. 1 PublicationCorresponds to variant dbSNP:rs199475612EnsemblClinVar.1
Natural variantiVAR_000901158R → Q in PKU; haplotypes 1,2,4,7,16, 28. 3 PublicationsCorresponds to variant dbSNP:rs5030843EnsemblClinVar.1
Natural variantiVAR_000902158R → W in PKU. Corresponds to variant dbSNP:rs75166491EnsemblClinVar.1
Natural variantiVAR_000903160Q → P in PKU. Corresponds to variant dbSNP:rs199475601EnsemblClinVar.1
Natural variantiVAR_000904161F → S in PKU; haplotype 4. Corresponds to variant dbSNP:rs79635844EnsemblClinVar.1
Natural variantiVAR_000905164I → T in PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs199475595EnsemblClinVar.1
Natural variantiVAR_000906167N → I in PKU. 1 PublicationCorresponds to variant dbSNP:rs77554925EnsemblClinVar.1
Natural variantiVAR_011568169R → H in PKU. Corresponds to variant dbSNP:rs199475679EnsemblClinVar.1
Natural variantiVAR_068001170H → Q in PKU; does not affect oligomerization. 2 PublicationsCorresponds to variant dbSNP:rs199475652EnsemblClinVar.1
Natural variantiVAR_000907170H → R in PKU. Corresponds to variant dbSNP:rs199475573EnsemblClinVar.1
Natural variantiVAR_000908171G → A in PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs199475596EnsemblClinVar.1
Natural variantiVAR_000909171G → R in PKU. Corresponds to variant dbSNP:rs199475613EnsemblClinVar.1
Natural variantiVAR_000910173P → T in PKU; haplotype 4. Corresponds to variant dbSNP:rs199475574EnsemblClinVar.1
Natural variantiVAR_000911174I → T in PKU; haplotype 1. Corresponds to variant dbSNP:rs138809906EnsemblClinVar.1
Natural variantiVAR_011570174I → V in PKU. Corresponds to variant dbSNP:rs199475632EnsemblClinVar.1
Natural variantiVAR_000912175P → A in PKU. Corresponds to variant dbSNP:rs199475604EnsemblClinVar.1
Natural variantiVAR_000914176R → P in PKU. Corresponds to variant dbSNP:rs74486803EnsemblClinVar.1
Natural variantiVAR_000915177V → L in PKU; haplotype 6. 1 PublicationCorresponds to variant dbSNP:rs199475602EnsemblClinVar.1
Natural variantiVAR_009243183E → Q in PKU. Corresponds to variant dbSNP:rs199475664EnsemblClinVar.1
Natural variantiVAR_000917190V → A in PKU; haplotype 3. 2 PublicationsCorresponds to variant dbSNP:rs62514919EnsemblClinVar.1
Natural variantiVAR_000918194L → P in PKU. Corresponds to variant dbSNP:rs5030844EnsemblClinVar.1
Natural variantiVAR_000919194Missing in PKU. 1
Natural variantiVAR_000920197Missing in PKU. 1
Natural variantiVAR_000921198Missing in PKU; haplotype 2. 1
Natural variantiVAR_000922201H → R in PKU. Corresponds to variant dbSNP:rs62517180EnsemblClinVar.1
Natural variantiVAR_000924204Y → C in PKU; mild; haplotypes 3,4. 1 PublicationCorresponds to variant dbSNP:rs62514927EnsemblClinVar.1
Natural variantiVAR_011571205E → A in PKU. Corresponds to variant dbSNP:rs62508593EnsemblClinVar.1
Natural variantiVAR_000925206Y → D in PKU. Corresponds to variant dbSNP:rs62517170EnsemblClinVar.1
Natural variantiVAR_000926207N → D in PKU. 1 PublicationCorresponds to variant dbSNP:rs62508572EnsemblClinVar.1
Natural variantiVAR_000927207N → S in PKU; severe; haplotype 4. 1 PublicationCorresponds to variant dbSNP:rs62508721EnsemblClinVar.1
Natural variantiVAR_000928211P → T in PKU; haplotype 4. Corresponds to variant dbSNP:rs62514931EnsemblClinVar.1
Natural variantiVAR_000929212L → P in PKU. Corresponds to variant dbSNP:rs62517198EnsemblClinVar.1
Natural variantiVAR_000930213L → P in PKU; severe. 1 PublicationCorresponds to variant dbSNP:rs62516109EnsemblClinVar.1
Natural variantiVAR_000931217C → G in PKU. Corresponds to variant dbSNP:rs62508718EnsemblClinVar.1
Natural variantiVAR_000932218G → V in PKU; haplotypes 1,2. Corresponds to variant dbSNP:rs62514933EnsemblClinVar.1
Natural variantiVAR_000933221E → G in PKU; haplotype 4. 1 PublicationCorresponds to variant dbSNP:rs62514934EnsemblClinVar.1
Natural variantiVAR_000934222D → V in PKU; haplotypes 3,4. Corresponds to variant dbSNP:rs62507319EnsemblClinVar.1
Natural variantiVAR_000935224I → M in PKU; haplotype 4. Corresponds to variant dbSNP:rs199475576EnsemblClinVar.1
Natural variantiVAR_000936225P → R in PKU. Corresponds to variant dbSNP:rs62517204EnsemblClinVar.1
Natural variantiVAR_000937225P → T in PKU; haplotype 1. Corresponds to variant dbSNP:rs199475589EnsemblClinVar.1
Natural variantiVAR_068003226Q → H in PKU. 1 PublicationCorresponds to variant dbSNP:rs62508615EnsemblClinVar.1
Natural variantiVAR_009244231S → F in PKU. Corresponds to variant dbSNP:rs62508577EnsemblClinVar.1
Natural variantiVAR_000939231S → P in PKU. Corresponds to variant dbSNP:rs5030845EnsemblClinVar.1
Natural variantiVAR_000940233F → L in PKU; haplotypes 2,3. Corresponds to variant dbSNP:rs62517208EnsemblClinVar.1
Natural variantiVAR_000941238T → P in PKU; haplotype 4. Corresponds to variant dbSNP:rs199475577EnsemblClinVar.1
Natural variantiVAR_000942239G → S in PKU. 1 PublicationCorresponds to variant dbSNP:rs62517178EnsemblClinVar.1
Natural variantiVAR_011572240F → S in PKU. Corresponds to variant dbSNP:rs62508594EnsemblClinVar.1
Natural variantiVAR_000944241R → H in PKU; haplotypes 1,5. Corresponds to variant dbSNP:rs62508730EnsemblClinVar.1
Natural variantiVAR_000945241R → L in PKU. Corresponds to variant dbSNP:rs62508730EnsemblClinVar.1
Natural variantiVAR_000946242L → F in PKU. Corresponds to variant dbSNP:rs199475578EnsemblClinVar.1
Natural variantiVAR_000948244P → L in PKU; haplotype 12. 1 PublicationCorresponds to variant dbSNP:rs118203923EnsemblClinVar.1
Natural variantiVAR_000949245V → A in PKU, HPA and non-PKU HPA; haplotypes 3,7. 4 PublicationsCorresponds to variant dbSNP:rs796052017EnsemblClinVar.1
Natural variantiVAR_000950245V → E in PKU; haplotype 11. Corresponds to variant dbSNP:rs76212747EnsemblClinVar.1
Natural variantiVAR_000951245V → L in PKU. Corresponds to variant dbSNP:rs62508694EnsemblClinVar.1
Natural variantiVAR_000952246A → D in PKU. Corresponds to variant dbSNP:rs199475610EnsemblClinVar.1
Natural variantiVAR_000953247G → V in PKU; haplotype 4. Corresponds to variant dbSNP:rs199475579EnsemblClinVar.1
Natural variantiVAR_000954248L → P in PKU. Corresponds to variant dbSNP:rs62507340EnsemblClinVar.1
Natural variantiVAR_000955249L → F in PKU; haplotype 1. Corresponds to variant dbSNP:rs74503222EnsemblClinVar.1
Natural variantiVAR_000956252R → G in PKU; haplotype 7. Corresponds to variant dbSNP:rs5030847EnsemblClinVar.1
Natural variantiVAR_000957252R → Q in PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs62644503EnsemblClinVar.1
Natural variantiVAR_000958252R → W in PKU; haplotypes 1,6,7,8,42, 69; complete loss of activity. 4 PublicationsCorresponds to variant dbSNP:rs5030847EnsemblClinVar.1
Natural variantiVAR_000960255L → S in PKU; haplotype 36. 1 PublicationCorresponds to variant dbSNP:rs62642930EnsemblClinVar.1
Natural variantiVAR_000959255L → V in PKU; haplotypes 18,21. Corresponds to variant dbSNP:rs62642931EnsemblClinVar.1
Natural variantiVAR_000961257G → C in PKU. Corresponds to variant dbSNP:rs5030848EnsemblClinVar.1
Natural variantiVAR_000962259A → T in PKU; haplotype 3. Corresponds to variant dbSNP:rs62642932EnsemblClinVar.1
Natural variantiVAR_000963259A → V in PKU; haplotypes 7,42. Corresponds to variant dbSNP:rs118203921EnsemblClinVar.1
Natural variantiVAR_000964261R → P in PKU. Corresponds to variant dbSNP:rs5030849EnsemblClinVar.1
Natural variantiVAR_000966263F → L in PKU. Corresponds to variant dbSNP:rs62642944EnsemblClinVar.1
Natural variantiVAR_000967264H → L in PKU. Corresponds to variant dbSNP:rs199475580EnsemblClinVar.1
Natural variantiVAR_000968265C → G in PKU. Corresponds to variant dbSNP:rs62517181EnsemblClinVar.1
Natural variantiVAR_000970270R → K in PKU. Corresponds to variant dbSNP:rs62514950EnsemblClinVar.1
Natural variantiVAR_000971270R → S in PKU; haplotype 1. Corresponds to variant dbSNP:rs62514951EnsemblClinVar.1
Natural variantiVAR_000972271H → Y in PKU. Corresponds to variant dbSNP:rs62517164EnsemblClinVar.1
Natural variantiVAR_000973273S → F in PKU; haplotype 7. Corresponds to variant dbSNP:rs62514953EnsemblClinVar.1
Natural variantiVAR_068004275P → L in PKU; reduced activity; increased affinity for the substrate; mildly reduced substrate activation; decreased cofactor affinity. 2 PublicationsCorresponds to variant dbSNP:rs62508715EnsemblClinVar.1
Natural variantiVAR_000974276M → I in PKU. Corresponds to variant dbSNP:rs62514954EnsemblClinVar.1
Natural variantiVAR_000975276M → V in PKU; haplotype 4. 1 PublicationCorresponds to variant dbSNP:rs62516149EnsemblClinVar.1
Natural variantiVAR_000976277Y → C in PKU. Corresponds to variant dbSNP:rs62516155EnsemblClinVar.1
Natural variantiVAR_000977277Y → D in PKU; haplotype 2. Corresponds to variant dbSNP:rs78655458EnsemblClinVar.1
Natural variantiVAR_000978278T → A in PKU. Corresponds to variant dbSNP:rs62516156EnsemblClinVar.1
Natural variantiVAR_000979278T → N in PKU. Corresponds to variant dbSNP:rs62507262EnsemblClinVar.1
Natural variantiVAR_000980280E → K in PKU; haplotypes 1,2,4,16,38; partial residual activity. 3 PublicationsCorresponds to variant dbSNP:rs62508698EnsemblClinVar.1
Natural variantiVAR_000981281P → L in PKU; haplotypes 1,4. 5 PublicationsCorresponds to variant dbSNP:rs5030851EnsemblClinVar.1
Natural variantiVAR_000982282D → N in PKU; haplotype 1. Corresponds to variant dbSNP:rs199475582EnsemblClinVar.1
Natural variantiVAR_000983283I → F in PKU; haplotype 21. Corresponds to variant dbSNP:rs62517168EnsemblClinVar.1
Natural variantiVAR_000984283I → N in PKU; severe. 1 PublicationCorresponds to variant dbSNP:rs62508693EnsemblClinVar.1
Natural variantiVAR_067758290H → Y in PKU. 1 Publication1
Natural variantiVAR_000985297R → C in PKU; haplotype 4. Corresponds to variant dbSNP:rs62642945EnsemblClinVar.1
Natural variantiVAR_000986297R → H in PKU. Corresponds to variant dbSNP:rs62642939EnsemblClinVar.1
Natural variantiVAR_000987299F → C in PKU; haplotype 8. 1 PublicationCorresponds to variant dbSNP:rs62642933EnsemblClinVar.1
Natural variantiVAR_000989300A → V in PKU. Corresponds to variant dbSNP:rs199475609EnsemblClinVar.1
Natural variantiVAR_000990303S → P in PKU; haplotype 5. Corresponds to variant dbSNP:rs199475608EnsemblClinVar.1
Natural variantiVAR_000991304Q → R in PKU. Corresponds to variant dbSNP:rs199475592EnsemblClinVar.1
Natural variantiVAR_000993309A → D in PKU; haplotype 7. Corresponds to variant dbSNP:rs62642935EnsemblClinVar.1
Natural variantiVAR_000994309A → V in PKU. Corresponds to variant dbSNP:rs62642935EnsemblClinVar.1
Natural variantiVAR_000995310S → F in PKU; haplotype 7. Corresponds to variant dbSNP:rs62642913EnsemblClinVar.1
Natural variantiVAR_000996311L → P in PKU; haplotypes 1,7,10. 2 PublicationsCorresponds to variant dbSNP:rs62642936EnsemblClinVar.1
Natural variantiVAR_000997314P → H in PKU. Corresponds to variant dbSNP:rs62642940EnsemblClinVar.1
Natural variantiVAR_011574318I → T in PKU; partial loss of activity. 1 PublicationCorresponds to variant dbSNP:rs62642918EnsemblClinVar.1
Natural variantiVAR_000998322A → G in PKU; haplotype 12. Corresponds to variant dbSNP:rs62514958EnsemblClinVar.1
Natural variantiVAR_000999322A → T in PKU; haplotype 1. Corresponds to variant dbSNP:rs62514957EnsemblClinVar.1
Natural variantiVAR_067759322A → V in PKU. 1 Publication1
Natural variantiVAR_009245325Y → C in PKU. Corresponds to variant dbSNP:rs62508578EnsemblClinVar.1
Natural variantiVAR_009246330E → D in PKU. Corresponds to variant dbSNP:rs62508580EnsemblClinVar.1
Natural variantiVAR_001000331F → L in PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs62517179EnsemblClinVar.1
Natural variantiVAR_001001333L → F in PKU. Corresponds to variant dbSNP:rs62516060EnsemblClinVar.1
Natural variantiVAR_001002334C → S in PKU. Corresponds to variant dbSNP:rs62517174EnsemblClinVar.1
Natural variantiVAR_001003337G → V in PKU. Corresponds to variant dbSNP:rs62517206EnsemblClinVar.1
Natural variantiVAR_001004338D → Y in PKU; haplotype 4. Corresponds to variant dbSNP:rs62516150EnsemblClinVar.1
Natural variantiVAR_001005341K → R in PKU. Corresponds to variant dbSNP:rs62516153EnsemblClinVar.1
Natural variantiVAR_001006341K → T in PKU. Corresponds to variant dbSNP:rs62516153EnsemblClinVar.1
Natural variantiVAR_001007342A → T in PKU; haplotype 5. Corresponds to variant dbSNP:rs62507282EnsemblClinVar.1
Natural variantiVAR_001008343Y → C in PKU. Corresponds to variant dbSNP:rs62507265EnsemblClinVar.1
Natural variantiVAR_009247344G → R in PKU. Corresponds to variant dbSNP:rs62508679EnsemblClinVar.1
Natural variantiVAR_009248344G → V in PKU. Corresponds to variant dbSNP:rs62508582EnsemblClinVar.1
Natural variantiVAR_001009345A → S in PKU. Corresponds to variant dbSNP:rs62516062EnsemblClinVar.1
Natural variantiVAR_001010345A → T in PKU; haplotype 7. Corresponds to variant dbSNP:rs62516062EnsemblClinVar.1
Natural variantiVAR_001011347L → F in PKU. Corresponds to variant dbSNP:rs62516154EnsemblClinVar.1
Natural variantiVAR_001012348L → V in PKU; mild haplotype 9. Corresponds to variant dbSNP:rs62516092EnsemblClinVar.1
Natural variantiVAR_001013349S → L in PKU; severe. 1 PublicationCorresponds to variant dbSNP:rs62507279EnsemblClinVar.1
Natural variantiVAR_001014349S → P in PKU; haplotypes 1,4. 1 PublicationCorresponds to variant dbSNP:rs62508646EnsemblClinVar.1
Natural variantiVAR_001015350S → T in PKU; haplotype 2. Corresponds to variant dbSNP:rs62517183EnsemblClinVar.1
Natural variantiVAR_011575357C → G in PKU. Corresponds to variant dbSNP:rs62508595EnsemblClinVar.1
Natural variantiVAR_001016362P → T in PKU. 1 PublicationCorresponds to variant dbSNP:rs62507329EnsemblClinVar.1
Natural variantiVAR_001018364 – 368Missing in PKU. 1 Publication5
Natural variantiVAR_001017364Missing in PKU; haplotype 5. 1 Publication1
Natural variantiVAR_001019366P → H in PKU. Corresponds to variant dbSNP:rs62516098EnsemblClinVar.1
Natural variantiVAR_001020372T → S in PKU. Corresponds to variant dbSNP:rs62517163EnsemblClinVar.1
Natural variantiVAR_001021377Y → C in PKU; haplotype 4. Corresponds to variant dbSNP:rs62642942EnsemblClinVar.1
Natural variantiVAR_001023386Y → C in PKU; common mutation. Corresponds to variant dbSNP:rs62516141EnsemblClinVar.1
Natural variantiVAR_001024387Y → H in PKU; haplotype 1. Corresponds to variant dbSNP:rs62517194EnsemblClinVar.1
Natural variantiVAR_001025388V → L in PKU. 1 PublicationCorresponds to variant dbSNP:rs62516101EnsemblClinVar.1
Natural variantiVAR_001026388V → M in PKU; haplotypes 1,4. Corresponds to variant dbSNP:rs62516101EnsemblClinVar.1
Natural variantiVAR_001028394D → A in PKU. Corresponds to variant dbSNP:rs62516102EnsemblClinVar.1
Natural variantiVAR_001029394D → H in PKU. 1 PublicationCorresponds to variant dbSNP:rs62516142EnsemblClinVar.1
Natural variantiVAR_001030395A → G in PKU. Corresponds to variant dbSNP:rs62508736EnsemblClinVar.1
Natural variantiVAR_001031395A → P in PKU; haplotype 1. Corresponds to variant dbSNP:rs62516103EnsemblClinVar.1
Natural variantiVAR_001032399 – 400Missing in PKU; haplotype 7. 2
Natural variantiVAR_068007407P → L in PKU. 1 PublicationCorresponds to variant dbSNP:rs62644473EnsemblClinVar.1
Natural variantiVAR_011576407P → S in PKU. Corresponds to variant dbSNP:rs62644465EnsemblClinVar.1
Natural variantiVAR_001034408R → Q in PKU; haplotypes 4,12. 1 PublicationCorresponds to variant dbSNP:rs5030859EnsemblClinVar.1
Natural variantiVAR_009249410F → S in PKU; mild. Corresponds to variant dbSNP:rs62644475EnsemblClinVar.1
Natural variantiVAR_001037413R → S in PKU; haplotype 1. Corresponds to variant dbSNP:rs62644467EnsemblClinVar.1
Natural variantiVAR_001039415D → N in PKU, HPA and non-PKU HPA; haplotype 1. 3 PublicationsCorresponds to variant dbSNP:rs62644499EnsemblClinVar.1
Natural variantiVAR_068008417Y → H in PKU; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. 2 PublicationsCorresponds to variant dbSNP:rs62644471EnsemblClinVar.1
Natural variantiVAR_001040418T → P in PKU; haplotype 4. Corresponds to variant dbSNP:rs62644501EnsemblClinVar.1
Natural variantiVAR_067760421I → S in PKU. 1 Publication1
Natural variantiVAR_001041430L → P in PKU. Corresponds to variant dbSNP:rs199475607EnsemblClinVar.1
Natural variantiVAR_001042447A → D in PKU. Corresponds to variant dbSNP:rs76542238EnsemblClinVar.1
Non-phenylketonuria hyperphenylalaninemia (Non-PKU HPA)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionMild form of phenylalanine hydroxylase deficiency characterized by phenylalanine levels persistently below 600 mumol, which allows normal intellectual and behavioral development without treatment. Non-PKU HPA is usually caused by the combined effect of a mild hyperphenylalaninemia mutation and a severe one.
See also OMIM:261600
Hyperphenylalaninemia (HPA)9 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionMildest form of phenylalanine hydroxylase deficiency.
See also OMIM:261600
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00923920Q → L in HPA. Corresponds to variant dbSNP:rs199475662EnsemblClinVar.1
Natural variantiVAR_009241110S → C in HPA. 1
Natural variantiVAR_069776121F → L in HPA. 1 Publication1
Natural variantiVAR_011567167N → S in HPA. Corresponds to variant dbSNP:rs77554925EnsemblClinVar.1
Natural variantiVAR_011569170H → D in HPA. Corresponds to variant dbSNP:rs199475655EnsemblClinVar.1
Natural variantiVAR_068002177V → M in HPA. 1 PublicationCorresponds to variant dbSNP:rs199475602EnsemblClinVar.1
Natural variantiVAR_069777196S → Y in HPA. 1 Publication1
Natural variantiVAR_068005310S → Y in HPA; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. 2 PublicationsCorresponds to variant dbSNP:rs62642913EnsemblClinVar.1
Natural variantiVAR_068006314P → S in HPA; does not affect oligomerization; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. 2 PublicationsCorresponds to variant dbSNP:rs199475650EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi283I → C: Loss of positive cooperativity and reduction of fold-activation by L-Phe preincubation. 1 Publication1

Keywords - Diseasei

Disease mutation, Phenylketonuria

Organism-specific databases

DisGeNETi5053
GeneReviewsiPAH
MalaCardsiPAH
MIMi261600 phenotype
OpenTargetsiENSG00000171759
Orphaneti79254 Classic phenylketonuria
2209 Maternal phenylketonuria
79651 Mild hyperphenylalaninemia
79253 Mild phenylketonuria
293284 Tetrahydrobiopterin-responsive hyperphenylalaninemia/phenylketonuria
PharmGKBiPA32911

Chemistry databases

ChEMBLiCHEMBL3076
DrugBankiDB03673 Beta(2-Thienyl)Alanine
DB06262 Droxidopa
DB00668 Epinephrine
DB00120 L-Phenylalanine
DB00368 Norepinephrine
DB04419 Norleucine
DB00360 Sapropterin
GuidetoPHARMACOLOGYi1240

Polymorphism and mutation databases

BioMutaiPAH
DMDMi129973

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002055481 – 452Phenylalanine-4-hydroxylaseAdd BLAST452

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei16Phosphoserine; by PKACombined sources1 Publication1

Post-translational modificationi

Phosphorylation at Ser-16 increases basal activity and facilitates activation by the substrate phenylalanine.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP00439
MaxQBiP00439
PaxDbiP00439
PeptideAtlasiP00439
PRIDEiP00439
ProteomicsDBi51249

2D gel databases

UCD-2DPAGEiP00439

PTM databases

iPTMnetiP00439
PhosphoSitePlusiP00439

Expressioni

Gene expression databases

BgeeiENSG00000171759 Expressed in 108 organ(s), highest expression level in nephron tubule
CleanExiHS_PAH
ExpressionAtlasiP00439 baseline and differential
GenevisibleiP00439 HS

Organism-specific databases

HPAiHPA028407
HPA031642

Interactioni

Subunit structurei

Homodimer and homotetramer.1 Publication

Protein-protein interaction databases

BioGridi111090, 4 interactors
DIPiDIP-58927N
IntActiP00439, 3 interactors
MINTiP00439
STRINGi9606.ENSP00000448059

Chemistry databases

BindingDBiP00439

Structurei

Secondary structure

1452
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP00439
SMRiP00439
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP00439

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini36 – 114ACTPROSITE-ProRule annotationAdd BLAST79

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3820 Eukaryota
COG3186 LUCA
GeneTreeiENSGT00390000010268
HOGENOMiHOG000233373
HOVERGENiHBG006841
InParanoidiP00439
KOiK00500
OMAiYEFFVEC
OrthoDBiEOG091G05MZ
PhylomeDBiP00439
TreeFamiTF313327

Family and domain databases

Gene3Di1.10.800.10, 1 hit
InterProiView protein in InterPro
IPR002912 ACT_dom
IPR001273 ArAA_hydroxylase
IPR018301 ArAA_hydroxylase_Fe/CU_BS
IPR036951 ArAA_hydroxylase_sf
IPR036329 Aro-AA_hydroxylase_C_sf
IPR019774 Aromatic-AA_hydroxylase_C
IPR005961 Phe-4-hydroxylase_tetra
IPR019773 Tyrosine_3-monooxygenase-like
PANTHERiPTHR11473 PTHR11473, 1 hit
PfamiView protein in Pfam
PF01842 ACT, 1 hit
PF00351 Biopterin_H, 1 hit
PIRSFiPIRSF000336 TH, 1 hit
PRINTSiPR00372 FYWHYDRXLASE
SUPFAMiSSF56534 SSF56534, 1 hit
TIGRFAMsiTIGR01268 Phe4hydrox_tetr, 1 hit
PROSITEiView protein in PROSITE
PS51671 ACT, 1 hit
PS00367 BH4_AAA_HYDROXYL_1, 1 hit
PS51410 BH4_AAA_HYDROXYL_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

P00439-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSTAVLENPG LGRKLSDFGQ ETSYIEDNCN QNGAISLIFS LKEEVGALAK
60 70 80 90 100
VLRLFEENDV NLTHIESRPS RLKKDEYEFF THLDKRSLPA LTNIIKILRH
110 120 130 140 150
DIGATVHELS RDKKKDTVPW FPRTIQELDR FANQILSYGA ELDADHPGFK
160 170 180 190 200
DPVYRARRKQ FADIAYNYRH GQPIPRVEYM EEEKKTWGTV FKTLKSLYKT
210 220 230 240 250
HACYEYNHIF PLLEKYCGFH EDNIPQLEDV SQFLQTCTGF RLRPVAGLLS
260 270 280 290 300
SRDFLGGLAF RVFHCTQYIR HGSKPMYTPE PDICHELLGH VPLFSDRSFA
310 320 330 340 350
QFSQEIGLAS LGAPDEYIEK LATIYWFTVE FGLCKQGDSI KAYGAGLLSS
360 370 380 390 400
FGELQYCLSE KPKLLPLELE KTAIQNYTVT EFQPLYYVAE SFNDAKEKVR
410 420 430 440 450
NFAATIPRPF SVRYDPYTQR IEVLDNTQQL KILADSINSE IGILCSALQK

IK
Length:452
Mass (Da):51,862
Last modified:July 21, 1986 - v1
Checksum:i018F00EBBBDDCE2F
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3KND8J3KND8_HUMAN
Phenylalanine-4-hydroxylase
PAH
447Annotation score:
F8W0A0F8W0A0_HUMAN
Phenylalanine-4-hydroxylase
PAH
136Annotation score:
F8W1D4F8W1D4_HUMAN
Phenylalanine-4-hydroxylase
PAH
117Annotation score:
A0A0U1RQY4A0A0U1RQY4_HUMAN
Phenylalanine-4-hydroxylase
PAH
143Annotation score:
A0A0U1RQI3A0A0U1RQI3_HUMAN
Phenylalanine-4-hydroxylase
PAH
149Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti183E → G in AAH26251 (PubMed:15489334).Curated1

Polymorphismi

The Glu-274 variant occurs on approximately 4% of African-American PAH alleles. The enzyme activity of the variant protein is indistinguishable from that of the wild-type form.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00086916S → P in PKU. Corresponds to variant dbSNP:rs62642946EnsemblClinVar.1
Natural variantiVAR_00923920Q → L in HPA. Corresponds to variant dbSNP:rs199475662EnsemblClinVar.1
Natural variantiVAR_00087039F → L in HPA and PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs62642926EnsemblClinVar.1
Natural variantiVAR_00087139Missing in PKU; haplotypes 9,21. 2 Publications1
Natural variantiVAR_00087240S → L in PKU. 1 PublicationCorresponds to variant dbSNP:rs62642938EnsemblClinVar.1
Natural variantiVAR_00087341L → F in PKU. Corresponds to variant dbSNP:rs62642928EnsemblClinVar.1
Natural variantiVAR_00924041L → P in PKU; mild. Corresponds to variant dbSNP:rs62642916EnsemblClinVar.1
Natural variantiVAR_00087442K → I in PKU; haplotype 21. Corresponds to variant dbSNP:rs62635346EnsemblClinVar.1
Natural variantiVAR_06799445V → A in PKU. 1 Publication1
Natural variantiVAR_00087546G → S in PKU; haplotype 5; significantly reduces phenylalanine binding. 1 PublicationCorresponds to variant dbSNP:rs74603784EnsemblClinVar.1
Natural variantiVAR_00087647A → V in non-PKU HPA; haplotype 4; significantly reduces phenylalanine binding. 1 PublicationCorresponds to variant dbSNP:rs118203925EnsemblClinVar.1
Natural variantiVAR_00087748L → S in PKU; mild; haplotypes 3,4. 5 PublicationsCorresponds to variant dbSNP:rs5030841EnsemblClinVar.1
Natural variantiVAR_00087853R → H in PKU. 1 PublicationCorresponds to variant dbSNP:rs118092776EnsemblClinVar.1
Natural variantiVAR_00087955F → L in HPA and PKU; does not affect oligomerization; results in loss of substrate activation. 3 PublicationsCorresponds to variant dbSNP:rs199475598EnsemblClinVar.1
Natural variantiVAR_00088056E → D in PKU; haplotype 10. Corresponds to variant dbSNP:rs199475567EnsemblClinVar.1
Natural variantiVAR_06799561N → D in PKU. 1 PublicationCorresponds to variant dbSNP:rs199475651EnsemblClinVar.1
Natural variantiVAR_06799662L → P in PKU. 1 Publication1
Natural variantiVAR_00088163 – 64TH → PN in PKU; haplotype 1; abolishes phenylalanine binding. 2
Natural variantiVAR_00088265I → N in PKU. 1 PublicationCorresponds to variant dbSNP:rs75193786EnsemblClinVar.1
Natural variantiVAR_06799765I → S in PKU; results in disturbed oligomerization; results in loss of substrate activation. 2 PublicationsCorresponds to variant dbSNP:rs75193786EnsemblClinVar.1
Natural variantiVAR_00088365I → T in PKU; haplotypes 1,5,9,21,B; abolishes phenylalanine binding. 3 PublicationsCorresponds to variant dbSNP:rs75193786EnsemblClinVar.1
Natural variantiVAR_06799865I → V in HPA and PKU. 2 PublicationsCorresponds to variant dbSNP:rs199475643EnsemblClinVar.1
Natural variantiVAR_00088467S → P in PKU; haplotype 4. Corresponds to variant dbSNP:rs5030842EnsemblClinVar.1
Natural variantiVAR_00088568R → S in PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs76394784EnsemblClinVar.1
Natural variantiVAR_00088676E → A in PKU. Corresponds to variant dbSNP:rs62507347EnsemblClinVar.1
Natural variantiVAR_06799976E → G in non-PKU HPA. 1 PublicationCorresponds to variant dbSNP:rs62507347EnsemblClinVar.1
Natural variantiVAR_00088784D → Y in PKU; haplotype 4. Corresponds to variant dbSNP:rs62514902EnsemblClinVar.1
Natural variantiVAR_00088887S → R in non-PKU HPA; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs62516151EnsemblClinVar.1
Natural variantiVAR_00088992T → I in PKU. Corresponds to variant dbSNP:rs62514903EnsemblClinVar.1
Natural variantiVAR_00089094Missing in PKU; mild; haplotype 2. 1 Publication1
Natural variantiVAR_00089198L → S in non-PKU HPA. 1 PublicationCorresponds to variant dbSNP:rs62517167EnsemblClinVar.1
Natural variantiVAR_000892104A → D in PKU; mild; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs62642929EnsemblClinVar.1
Natural variantiVAR_009241110S → C in HPA. 1
Natural variantiVAR_069776121F → L in HPA. 1 Publication1
Natural variantiVAR_000893124T → I in PKU; haplotype 28. Corresponds to variant dbSNP:rs199475571EnsemblClinVar.1
Natural variantiVAR_000894129D → Y in PKU. Corresponds to variant dbSNP:rs199475606EnsemblClinVar.1
Natural variantiVAR_000895143D → G in PKU; haplotype 11. 1 PublicationCorresponds to variant dbSNP:rs199475572EnsemblClinVar.1
Natural variantiVAR_011566145D → V in PKU. Corresponds to variant dbSNP:rs140175796EnsemblClinVar.1
Natural variantiVAR_000896146H → Y in PKU. Corresponds to variant dbSNP:rs199475599EnsemblClinVar.1
Natural variantiVAR_000897148G → S in PKU; haplotypes 1,2,7. Corresponds to variant dbSNP:rs80297647EnsemblClinVar.1
Natural variantiVAR_000898151D → H in PKU; haplotypes 1,8. Corresponds to variant dbSNP:rs199475597EnsemblClinVar.1
Natural variantiVAR_000899154Y → N in PKU. Corresponds to variant dbSNP:rs199475587EnsemblClinVar.1
Natural variantiVAR_009242155R → P in PKU. Corresponds to variant dbSNP:rs199475663EnsemblClinVar.1
Natural variantiVAR_000900157R → N in PKU; severe; 5% activity; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_068000157R → S in PKU. 1 PublicationCorresponds to variant dbSNP:rs199475612EnsemblClinVar.1
Natural variantiVAR_000901158R → Q in PKU; haplotypes 1,2,4,7,16, 28. 3 PublicationsCorresponds to variant dbSNP:rs5030843EnsemblClinVar.1
Natural variantiVAR_000902158R → W in PKU. Corresponds to variant dbSNP:rs75166491EnsemblClinVar.1
Natural variantiVAR_000903160Q → P in PKU. Corresponds to variant dbSNP:rs199475601EnsemblClinVar.1
Natural variantiVAR_000904161F → S in PKU; haplotype 4. Corresponds to variant dbSNP:rs79635844EnsemblClinVar.1
Natural variantiVAR_000905164I → T in PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs199475595EnsemblClinVar.1
Natural variantiVAR_000906167N → I in PKU. 1 PublicationCorresponds to variant dbSNP:rs77554925EnsemblClinVar.1
Natural variantiVAR_011567167N → S in HPA. Corresponds to variant dbSNP:rs77554925EnsemblClinVar.1
Natural variantiVAR_011568169R → H in PKU. Corresponds to variant dbSNP:rs199475679EnsemblClinVar.1
Natural variantiVAR_011569170H → D in HPA. Corresponds to variant dbSNP:rs199475655EnsemblClinVar.1
Natural variantiVAR_068001170H → Q in PKU; does not affect oligomerization. 2 PublicationsCorresponds to variant dbSNP:rs199475652EnsemblClinVar.1
Natural variantiVAR_000907170H → R in PKU. Corresponds to variant dbSNP:rs199475573EnsemblClinVar.1
Natural variantiVAR_000908171G → A in PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs199475596EnsemblClinVar.1
Natural variantiVAR_000909171G → R in PKU. Corresponds to variant dbSNP:rs199475613EnsemblClinVar.1
Natural variantiVAR_000910173P → T in PKU; haplotype 4. Corresponds to variant dbSNP:rs199475574EnsemblClinVar.1
Natural variantiVAR_000911174I → T in PKU; haplotype 1. Corresponds to variant dbSNP:rs138809906EnsemblClinVar.1
Natural variantiVAR_011570174I → V in PKU. Corresponds to variant dbSNP:rs199475632EnsemblClinVar.1
Natural variantiVAR_000912175P → A in PKU. Corresponds to variant dbSNP:rs199475604EnsemblClinVar.1
Natural variantiVAR_000913176R → L in non-PKU HPA. 1 PublicationCorresponds to variant dbSNP:rs74486803EnsemblClinVar.1
Natural variantiVAR_000914176R → P in PKU. Corresponds to variant dbSNP:rs74486803EnsemblClinVar.1
Natural variantiVAR_000915177V → L in PKU; haplotype 6. 1 PublicationCorresponds to variant dbSNP:rs199475602EnsemblClinVar.1
Natural variantiVAR_068002177V → M in HPA. 1 PublicationCorresponds to variant dbSNP:rs199475602EnsemblClinVar.1
Natural variantiVAR_000916178E → G in non-PKU HPA. 1 PublicationCorresponds to variant dbSNP:rs77958223EnsemblClinVar.1
Natural variantiVAR_009243183E → Q in PKU. Corresponds to variant dbSNP:rs199475664EnsemblClinVar.1
Natural variantiVAR_000917190V → A in PKU; haplotype 3. 2 PublicationsCorresponds to variant dbSNP:rs62514919EnsemblClinVar.1
Natural variantiVAR_000918194L → P in PKU. Corresponds to variant dbSNP:rs5030844EnsemblClinVar.1
Natural variantiVAR_000919194Missing in PKU. 1
Natural variantiVAR_069777196S → Y in HPA. 1 Publication1
Natural variantiVAR_000920197Missing in PKU. 1
Natural variantiVAR_000921198Missing in PKU; haplotype 2. 1
Natural variantiVAR_000922201H → R in PKU. Corresponds to variant dbSNP:rs62517180EnsemblClinVar.1
Natural variantiVAR_000923201H → Y in non-PKU HPA; haplotype 1. 2 PublicationsCorresponds to variant dbSNP:rs62517205EnsemblClinVar.1
Natural variantiVAR_000924204Y → C in PKU; mild; haplotypes 3,4. 1 PublicationCorresponds to variant dbSNP:rs62514927EnsemblClinVar.1
Natural variantiVAR_011571205E → A in PKU. Corresponds to variant dbSNP:rs62508593EnsemblClinVar.1
Natural variantiVAR_000925206Y → D in PKU. Corresponds to variant dbSNP:rs62517170EnsemblClinVar.1
Natural variantiVAR_000926207N → D in PKU. 1 PublicationCorresponds to variant dbSNP:rs62508572EnsemblClinVar.1
Natural variantiVAR_000927207N → S in PKU; severe; haplotype 4. 1 PublicationCorresponds to variant dbSNP:rs62508721EnsemblClinVar.1
Natural variantiVAR_000928211P → T in PKU; haplotype 4. Corresponds to variant dbSNP:rs62514931EnsemblClinVar.1
Natural variantiVAR_000929212L → P in PKU. Corresponds to variant dbSNP:rs62517198EnsemblClinVar.1
Natural variantiVAR_000930213L → P in PKU; severe. 1 PublicationCorresponds to variant dbSNP:rs62516109EnsemblClinVar.1
Natural variantiVAR_000931217C → G in PKU. Corresponds to variant dbSNP:rs62508718EnsemblClinVar.1
Natural variantiVAR_000932218G → V in PKU; haplotypes 1,2. Corresponds to variant dbSNP:rs62514933EnsemblClinVar.1
Natural variantiVAR_000933221E → G in PKU; haplotype 4. 1 PublicationCorresponds to variant dbSNP:rs62514934EnsemblClinVar.1
Natural variantiVAR_000934222D → V in PKU; haplotypes 3,4. Corresponds to variant dbSNP:rs62507319EnsemblClinVar.1
Natural variantiVAR_000935224I → M in PKU; haplotype 4. Corresponds to variant dbSNP:rs199475576EnsemblClinVar.1
Natural variantiVAR_000936225P → R in PKU. Corresponds to variant dbSNP:rs62517204EnsemblClinVar.1
Natural variantiVAR_000937225P → T in PKU; haplotype 1. Corresponds to variant dbSNP:rs199475589EnsemblClinVar.1
Natural variantiVAR_068003226Q → H in PKU. 1 PublicationCorresponds to variant dbSNP:rs62508615EnsemblClinVar.1
Natural variantiVAR_000938230V → I in non-PKU HPA; haplotype 4. 1 PublicationCorresponds to variant dbSNP:rs62516152EnsemblClinVar.1
Natural variantiVAR_009244231S → F in PKU. Corresponds to variant dbSNP:rs62508577EnsemblClinVar.1
Natural variantiVAR_000939231S → P in PKU. Corresponds to variant dbSNP:rs5030845EnsemblClinVar.1
Natural variantiVAR_000940233F → L in PKU; haplotypes 2,3. Corresponds to variant dbSNP:rs62517208EnsemblClinVar.1
Natural variantiVAR_000941238T → P in PKU; haplotype 4. Corresponds to variant dbSNP:rs199475577EnsemblClinVar.1
Natural variantiVAR_000942239G → S in PKU. 1 PublicationCorresponds to variant dbSNP:rs62517178EnsemblClinVar.1
Natural variantiVAR_011572240F → S in PKU. Corresponds to variant dbSNP:rs62508594EnsemblClinVar.1
Natural variantiVAR_000943241R → C in non-PKU HPA and PKU; haplotype 34. 3 PublicationsCorresponds to variant dbSNP:rs76687508EnsemblClinVar.1
Natural variantiVAR_000944241R → H in PKU; haplotypes 1,5. Corresponds to variant dbSNP:rs62508730EnsemblClinVar.1
Natural variantiVAR_000945241R → L in PKU. Corresponds to variant dbSNP:rs62508730EnsemblClinVar.1
Natural variantiVAR_000946242L → F in PKU. Corresponds to variant dbSNP:rs199475578EnsemblClinVar.1
Natural variantiVAR_000947243R → Q in non-PKU HPA and PKU; haplotypes 4,7,9. 2 PublicationsCorresponds to variant dbSNP:rs62508588EnsemblClinVar.1
Natural variantiVAR_000948244P → L in PKU; haplotype 12. 1 PublicationCorresponds to variant dbSNP:rs118203923EnsemblClinVar.1
Natural variantiVAR_000949245V → A in PKU, HPA and non-PKU HPA; haplotypes 3,7. 4 PublicationsCorresponds to variant dbSNP:rs796052017EnsemblClinVar.1
Natural variantiVAR_000950245V → E in PKU; haplotype 11. Corresponds to variant dbSNP:rs76212747EnsemblClinVar.1
Natural variantiVAR_000951245V → L in PKU. Corresponds to variant dbSNP:rs62508694EnsemblClinVar.1
Natural variantiVAR_000952246A → D in PKU. Corresponds to variant dbSNP:rs199475610EnsemblClinVar.1
Natural variantiVAR_000953247G → V in PKU; haplotype 4. Corresponds to variant dbSNP:rs199475579EnsemblClinVar.1
Natural variantiVAR_000954248L → P in PKU. Corresponds to variant dbSNP:rs62507340EnsemblClinVar.1
Natural variantiVAR_000955249L → F in PKU; haplotype 1. Corresponds to variant dbSNP:rs74503222EnsemblClinVar.1
Natural variantiVAR_000956252R → G in PKU; haplotype 7. Corresponds to variant dbSNP:rs5030847EnsemblClinVar.1
Natural variantiVAR_000957252R → Q in PKU; haplotype 1. 1 PublicationCorresponds to variant dbSNP:rs62644503EnsemblClinVar.1
Natural variantiVAR_000958252R → W in PKU; haplotypes 1,6,7,8,42, 69; complete loss of activity. 4 PublicationsCorresponds to variant dbSNP:rs5030847EnsemblClinVar.1
Natural variantiVAR_000960255L → S in PKU; haplotype 36. 1 PublicationCorresponds to variant dbSNP:rs62642930EnsemblClinVar.1
Natural variantiVAR_000959255L → V in PKU; haplotypes 18,21. Corresponds to variant dbSNP:rs62642931EnsemblClinVar.1
Natural variantiVAR_000961257G → C in PKU. Corresponds to variant dbSNP:rs5030848EnsemblClinVar.1
Natural variantiVAR_000962259A → T in PKU; haplotype 3. Corresponds to variant dbSNP:rs62642932EnsemblClinVar.1
Natural variantiVAR_000963259A → V in PKU; haplotypes 7,42. Corresponds to variant dbSNP:rs118203921EnsemblClinVar.1
Natural variantiVAR_000964261R → P in PKU. Corresponds to variant dbSNP:rs5030849EnsemblClinVar.1
Natural variantiVAR_000965261R → Q in HPA and PKU; mild; haplotypes 1,2,4,22, 24,28. 5 PublicationsCorresponds to variant dbSNP:rs5030849EnsemblClinVar.1
Natural variantiVAR_000966263F → L in PKU. Corresponds to variant dbSNP:rs62642944EnsemblClinVar.1
Natural variantiVAR_000967264H → L in PKU. Corresponds to variant dbSNP:rs199475580EnsemblClinVar.1
Natural variantiVAR_000968265C → G in PKU. Corresponds to variant dbSNP:rs62517181EnsemblClinVar.1
Natural variantiVAR_000969269I → L in non-PKU HPA. 1 PublicationCorresponds to variant dbSNP:rs62508692EnsemblClinVar.1
Natural variantiVAR_000970270R → K in PKU. Corresponds to variant dbSNP:rs62514950EnsemblClinVar.1
Natural variantiVAR_000971270R → S in PKU; haplotype 1. Corresponds to variant dbSNP:rs62514951EnsemblClinVar.1
Natural variantiVAR_000972271H → Y in PKU. Corresponds to variant dbSNP:rs62517164EnsemblClinVar.1
Natural variantiVAR_000973273S → F in PKU; haplotype 7. Corresponds to variant dbSNP:rs62514953EnsemblClinVar.1
Natural variantiVAR_011573274K → E1 PublicationCorresponds to variant dbSNP:rs142934616EnsemblClinVar.1
Natural variantiVAR_068004275P → L in PKU; reduced activity; increased affinity for the substrate; mildly reduced substrate activation; decreased cofactor affinity. 2 PublicationsCorresponds to variant dbSNP:rs62508715EnsemblClinVar.1
Natural variantiVAR_000974276M → I in PKU. Corresponds to variant dbSNP:rs62514954EnsemblClinVar.1
Natural variantiVAR_000975276M → V in PKU; haplotype 4. 1 PublicationCorresponds to variant dbSNP:rs62516149EnsemblClinVar.1
Natural variantiVAR_000976277Y → C in PKU. Corresponds to variant dbSNP:rs62516155EnsemblClinVar.1
Natural variantiVAR_000977277Y → D in PKU; haplotype 2. Corresponds to variant dbSNP:rs78655458EnsemblClinVar.1
Natural variantiVAR_000978278T → A in PKU. Corresponds to variant dbSNP:rs62516156EnsemblClinVar.1
Natural variantiVAR_000979278T → N in PKU. Corresponds to variant dbSNP:rs62507262EnsemblClinVar.1
Natural variantiVAR_000980280E → K in PKU; haplotypes 1,2,4,16,38; partial residual activity. 3 PublicationsCorresponds to variant dbSNP:rs62508698EnsemblClinVar.1
Natural variantiVAR_000981281P → L in PKU; haplotypes 1,4. 5 Publications