What type of protein is HTT?

Normal huntingtin (htt) is a protein of 3144 amino acids and is 348 kD. Despite its size, native htt is completely soluble in the cell; it localizes to the nucleus, the endoplasmic reticulum, and the Golgi apparatus. In neurons, it is also found in neurites and at the synapses.

What is the HTT mutation?

The HTT mutation that causes Huntington disease involves a DNA segment known as a CAG trinucleotide repeat . This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated 10 to 35 times within the gene.

What does mutant HTT do?

The HTT gene provides instructions for making a protein called huntingtin. Although the exact function of this protein is unknown, it appears to play an important role in nerve cells (neurons) in the brain and is essential for normal development before birth.

What protein does CAG code for?

Everyone has a gene that codes for huntingtin protein, a protein found in the cells of the body, which we will discuss later. Towards the beginning of this gene, the three-letter codon sequence C-A-G is repeated a few times. Each C-A-G sequence codes for the amino acid glutamine, a protein building block.

What does mutated huntingtin protein do?

Although the signaling pathways involved in HD are not yet clearly elucidated, mutant huntingtin protein is a key factor in the induction of neurodegeneration. The mutant huntingtin protein alters intracellular Ca2+ homeostasis, disrupts intracellular trafficking and impairs gene transcription.

How many proteins does huntingtin interact with?

Huntingtin mediated trafficking of vesicles and organelles. Htt, with its large number of protein-protein interaction domains, has been found to interact so far with over 200 other proteins [45, 46, 91, 92].

Where is HTT found?

The HTT gene is located on the short arm (p) of chromosome 4 at position 16.3, from base pair 3,074,510 to base pair 3,243,960.

Does everyone have the HTT gene?

Everyone has this sequence but the number of times it is repeated varies. Mutations in the HTT gene affect the number of repeated sequences. There is a range of values that indicate HD status.

How is Huntington’s disease confirmed?

The most effective and accurate method of testing for HD—called the direct genetic test—counts the number of CAG repeats in the HD gene, using DNA taken from a blood sample. The presence of 36 or more repeats supports a diagnosis of HD. A test result of 26 or fewer repeats rules out HD.

Where is the HTT gene?

Does everyone have HTT gene?

Inheritance. The HTT gene is found on chromosome 4, of which every person has two copies, one inherited from each biological parent. Huntington’s is an autosomal dominant disorder, meaning that a mutation in only one of the two copies of the gene is sufficient to cause the disease.