PAH
Chr 12ARphenylalanine hydroxylase
The encoded phenylalanine hydroxylase enzyme hydroxylates phenylalanine to tyrosine as the rate-limiting step in phenylalanine catabolism. Mutations cause autosomal recessive phenylketonuria and milder hyperphenylalaninemia through deficiency of enzyme activity. Loss of function mutations result in accumulation of phenylalanine and its metabolites, leading to intellectual disability if untreated.
Definitive — sufficient evidence for diagnostic panels
Some data sources returned errors (1)
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PAH · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Risk and Resilience in Pulmonary Arterial Hypertension and Genetically Susceptible Individuals
RECRUITINGTrial for Treatment of High Risk BC With Two Sequences of Neoadjuvant Chemotherapy With Pembrolizumab
NOT YET RECRUITINGPaclitaxel & Cyclophosphamide With or Without Trastuzumab Before Surgery in Treating Previously Untreated Breast Cancer
ACTIVE NOT RECRUITINGNeoadjuvant Pembrolizumab + Decitabine Followed by Std Neoadj Chemo for Locally Advanced HER2- Breast Ca
ACTIVE NOT RECRUITINGi-NEED: NEw migrainE Drugs Database
RECRUITINGMitoxantrone for Venetoclax Resistant Acute Myeloid Leukemia
RECRUITINGRevumenib in Combination With 7+3 + Midostaurin in AML
RECRUITINGPredicting and Preventing Adverse Maternal and Child Outcomes of Opioid Use Disorder in Pregnancy
RECRUITINGGene Therapy in Treating Patients With Human Immunodeficiency Virus-Related Lymphoma Receiving Stem Cell Transplant
ACTIVE NOT RECRUITINGNordicTrip, a Translational Study of Preoperative Chemotherapy in TNBC
ACTIVE NOT RECRUITINGDetermine Effectiveness of Anifrolumab In SYstemic Sclerosis (DAISY)
ACTIVE NOT RECRUITINGLipid Balance in Adult Sickle Cell Patients
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools