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Genetic Archaeology
GENETIC ARCHAEOLOGY // PROFILE

PAH

Phenylalanine Hydroxylase

CHR 12

Overview

The PAH gene encodes the enzyme that converts phenylalanine into tyrosine. A deficiency leads to the accumulation of phenylalanine in the brain.

📍 Chromosome

12q23.2 (Chromosome 12)

🧬 Category

Metabolism

🔬 Inheritance

Autosomal recessive

📊 Prevalence

1:10,000 in Europe

Associated Diseases

  • 🧠 Phenylketonuria (PKU)

    If untreated, severe intellectual disability due to phenylalanine accumulation.

  • 🧠 Mild Hyperphenylalaninemia

    Less severe form with residual enzyme activity.

🧬 Relevant SNPs

rs5030858
12:102836889
Ref

C

/

Alt

T

Significance: Classical PKU mutation (p.Arg408Trp). Most common variant in Europe.

rs62514895
12:102851898
Ref

G

/

Alt

A

Significance: Splice mutation (IVS12+1G>A), associated with severe clinical courses.

⚕️ Clinical Management

Low-phenylalanine diet from birth (newborn screening). Possible sapropterin therapy.

📚 Data Sources

  • Source: OMIM: #612349
  • Source: dbSNP: rs5030858
  • Source: PKU Guidelines

Biological Function

PAH catalyzes the first step in phenylalanine degradation. Deficiency leads to toxic accumulation of phenylalanine in blood and brain.

Associated Conditions

Phenylketonuria (PKU) Hyperphenylalaninemia (mild form) Classic PKU Atypical PKU
Molecular Analysis

Analyzed Markers

ID Unknown Pathogenic
Pos: chr12:102836889 | Alleles: -/-

Arg408Trp - Most common PKU mutation in Europe (~30% of alleles). Leads to classic PKU.

ID Unknown Pathogenic
Pos: chr12:102851898 | Alleles: -/-

IVS12+1 G>A - Severe PKU. Second most common mutation in some populations.