PRNP gene
The PRNP gene provides instructions for making the prion protein (PrP), which is active in the brain and may play a role in neuroprotection and cell-to-cell communication.
Normal Function
The PRNP gene provides instructions for making the prion protein (PrP). While its precise function is unknown, researchers believe it plays a role in transporting copper into cells, protecting neurons (neuroprotection), and forming synapses for cell-to-cell communication. There are two primary forms of this protein: the normal version, PrPC, and the abnormal version, PrPSc.
Health Conditions Related to Genetic Changes
Huntington's disease-like 1 (HDL1)
A specific variant in the PRNP gene causes HDL1, a condition with symptoms resembling Huntington's disease, including uncontrolled movements, emotional problems, and cognitive decline.
- Mechanism: The variant involves an expansion of a DNA segment that codes for an octapeptide (a protein fragment of eight amino acids). While normally repeated four times, in HDL1, this segment is repeated six or more times.
- Consequence: This leads to an abnormally long version of PrP that builds up in the brain, contributing to the loss of neurons.
Prion disease
Variants in the PRNP gene are linked to familial prion diseases, such as Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI). These conditions cause dementia, ataxia (poor coordination), and personality changes.
- Mechanism: Genetic variants alter the structure of PrP, leading to the production of the abnormal PrPSc. This abnormal protein binds to normal PrPC and transforms it into more PrPSc.
- Consequence: The buildup of PrPSc forms clumps that destroy neurons, creating microscopic sponge-like holes (vacuoles) in the brain.
- Risk Factors: A common polymorphism at position 129 of the protein (Met129Val) influences the risk and progression of these diseases. Individuals with the same amino acid at both positions (Met/Met or Val/Val) are more susceptible to earlier onset and rapid worsening of symptoms.
Wilson disease
The Met129Val polymorphism has been shown to influence the onset and symptoms of Wilson disease, a disorder of copper accumulation. People with the Met/Met genotype at position 129 may experience a later onset of symptoms and are more likely to develop neurological symptoms, such as tremors.
Other Names for This Gene
- PRIP
- PrP