PAH

Chr 12

phenylalanine hydroxylase

Also known as: PH, PKU, PKU1

This gene encodes a member of the biopterin-dependent aromatic amino acid hydroxylase protein family. The encoded phenylalanine hydroxylase enzyme hydroxylates phenylalanine to tyrosine and is the rate-limiting step in phenylalanine catabolism. Deficiency of this enzyme activity results in the autosomal recessive disorder phenylketonuria. [provided by RefSeq, Aug 2017]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPhenylalanine hydroxylase deficiency

Clinical highlights

Gene-disease validity (ClinGen)
phenylketonuria · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
12
Active trials
3276
Pubs (1 yr)
P/LP submissions
P/LP missense
1.50
LOEUF
LOF
Mechanism· G2P
📖
GeneReview available — PAH
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.50LOEUF
pLI 0.000
Z-score -0.59
OE 1.12 (0.841.50)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.65Z-score
OE missense 1.12 (1.011.24)
271 obs / 242.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?1.12 (0.841.50)
00.351.4
Missense OE?1.12 (1.011.24)
00.61.4
Synonymous OE?1.11
01.21.6
LoF obs/exp: 32 / 28.6Missense obs/exp: 271 / 242.6Syn Z: -0.83

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.

VCEP specificationsPhenylketonuriaReleased
Panel ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Anatomic Stage II Breast Cancer AJCC v8Anatomic Stage IIA Breast Cancer AJCC v8Anatomic Stage IIB Breast Cancer AJCC v8

CompassHER2-pCR: Decreasing Chemotherapy for Breast Cancer Patients After Pre-surgery Chemo and Targeted Therapy

ACTIVE NOT RECRUITING
NCT04266249Phase PHASE2ECOG-ACRIN Cancer Research GroupStarted 2020-03-13
DocetaxelLumpectomyMastectomy
Hypertension, Resistant to Conventional Therapy

Antihypertensive Mechanisms of Minocycline in Resistant Hypertension

RECRUITING
NCT06246396Phase PHASE4University of FloridaStarted 2025-01-08
Minocycline HydrochloridePlacebo
Systemic SclerosisScleroderma

Determine Effectiveness of Anifrolumab In SYstemic Sclerosis (DAISY)

ACTIVE NOT RECRUITING
NCT05925803Phase PHASE3AstraZenecaStarted 2023-11-08
Anifrolumab (blinded)Placebo (blinded)Anifrolumab (unblinded, open label)
Gastric Cancer Peritoneal Metastases

PIPAC in Gastric Peritoneal Metastasis

ENROLLING BY INVITATION
NCT07517419Phase PHASE2Chinese University of Hong KongStarted 2021-10-11
Cisplatin and Doxorubicin
Multiple Myeloma

S1803, Lenalidomide +/- Daratumumab/rHuPh20 as Post-ASCT Maintenance for MM w/MRD to Direct Therapy Duration

ACTIVE NOT RECRUITING
NCT04071457Phase PHASE3SWOG Cancer Research NetworkStarted 2019-08-13
LenalidomideDaratumumab/rHuPH20
Ganglioneuroblastoma, NodularNeuroblastoma

Dinutuximab With Chemotherapy, Surgery and Stem Cell Transplantation for the Treatment of Children With Newly Diagnosed High Risk Neuroblastoma

RECRUITING
NCT06172296Phase PHASE3National Cancer Institute (NCI)Started 2024-04-19
Biospecimen CollectionBone Marrow AspirationBone Marrow Biopsy
Acute Myeloid LeukemiaNPM1 MutationIDH1 Mutation

Study on the Efficacy and Safety of VA Regimen Compared to "3+7" Regimen in Newly Diagnosed AML With NPM1 or IDH1/IDH2 Mutations

NOT YET RECRUITING
NCT07664839Phase PHASE2Shen yangStarted 2026-07-01
VEN combined with azacitidineCytarabine plus Daunorubicin
AMLRefractoryRelapsed

Multicenter, Platform-type Clinical Study of Refractory/Recurrent Acute Myeloid Leukemia

RECRUITING
NCT06265545Phase NAInstitute of Hematology & Blood Diseases Hospital, ChinaStarted 2024-02-22
IvosidenibVenetoclaxGilteritinib
Lung CancerLung InfectionCOPD

Identification of Multiple Pulmonary Diseases Using Volatile Organic Compounds Biomarkers in Human Exhaled Breath

RECRUITING
NCT06528418ChromX HealthStarted 2024-06-30
Gas chromatography-mass spectrometry(GC-MS) and micro Gas Chromatography-photoionisation detector (μGC-PID) system
Opioid Use DisorderPregnancy Related

Predicting and Preventing Adverse Maternal and Child Outcomes of Opioid Use Disorder in Pregnancy

RECRUITING
NCT05942313Ilana HullStarted 2023-08-28
Buprenorphine/ Methadone exposure
Breast Ductal Carcinoma In SituInvasive Breast CarcinomaStage II Breast Cancer AJCC v6 and v7

Breast Cancer WEight Loss Study (BWEL Study)

ACTIVE NOT RECRUITING
NCT02750826Phase PHASE3Alliance for Clinical Trials in OncologyStarted 2016-09-16
Health Education ProgramWeight Loss Intervention
Extrapulmonary Small Cell Carcinoma

AGNOSTIC THERAPY IN A PHASE II SINGLE-ARM STUDY IN FIRST-LINE TREATMENT OF DURVALUMAB IN ASSOCIATION WITH CARBOPLATIN OR CISPLATIN AND ETOPOSIDE IN PATIENTS AFFECTED BY EXTENSIVE STAGE - EXTRAPULMONARY SMALL CELL CARCINOMA

RECRUITING
NCT06464068Phase PHASE2Gruppo Oncologico Italiano di Ricerca ClinicaStarted 2024-01-16
Durvalumab