HINT1 gene
The HINT1 gene encodes a protein involved in nervous system function and cell regulation, with mutations linked to a specific form of axonal neuropathy.
Normal Function
The HINT1 gene provides instructions for making a protein called histidine triad nucleotide-binding protein 1 (HINT1). While the exact function is not fully clear, laboratory studies show that HINT1 has the ability to bind to nucleotides and break them down through a process called hydrolysis.
The HINT1 protein is involved in the nervous system. In nerve cells (neurons), HINT1 binds to signaling proteins called receptors that relay signals affecting nervous system function. HINT1 appears to stabilize the interaction of different receptors and regulate the effects of their signaling.
Additionally, HINT1 is involved in programmed cell death (apoptosis) and acts as a tumor suppressor by blocking the activity of certain genes, preventing cells from growing and dividing too rapidly or in an uncontrolled way.
Health Conditions Related to Genetic Changes
Autosomal recessive axonal neuropathy with neuromyotonia
At least nine mutations in the HINT1 gene have been found to cause autosomal recessive axonal neuropathy with neuromyotonia. This neurological condition affects the peripheral nerves, which connect the brain and spinal cord to muscles and sensory cells.
Common signs and symptoms include:
- Muscle weakness in the feet, legs, and hands
- Delayed relaxation of muscles after tensing (neuromyotonia)
- Mildly impaired sensations in some individuals
The HINT1 gene mutations that cause this condition change single amino acids in the HINT1 protein, reducing or eliminating the protein's ability to perform the hydrolysis reaction. Sometimes the altered protein is broken down prematurely. It is not yet clear how the loss of functional HINT1 protein leads to the specific signs and symptoms of this condition.
Charcot-Marie-Tooth disease
Mutations in the HINT1 gene have also been associated with Charcot-Marie-Tooth disease.