GRN gene
granulin precursor
The GRN gene provides instructions for making a protein called granulin (also known as progranulin). This protein is found in tissues throughout the body. It is most active in cells that are dividing rapidly, such as skin cells and cells that line the gastrointestinal tract. Granulin helps regulate the growth, division, and survival of these cells. It also plays important roles in early embryonic development, regulation of the body's immune system response, and wound healing.
Granulin is active in several types of brain cells, although much less is known about this protein's function in the brain. It appears to be critical for the survival of nerve cells (neurons).
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More than 65 mutations in the GRN gene have been identified in people with GRN-related frontotemporal dementia. The most common mutation, which is written as Arg493Ter or R493X, creates a premature stop signal in the instructions for making granulin. Most of the mutations that cause GRN-related frontotemporal dementia prevent any protein from being produced from one copy of the GRN gene in each cell. As a result of these genetic changes, cells make only half the usual amount of granulin.
It is unclear how a shortage of granulin leads to the features of GRN-related frontotemporal dementia. However, studies have shown that the disorder is characterized by the buildup of a protein called TAR DNA-binding protein (TDP-43) in certain brain cells. The TDP-43 protein forms clumps (aggregates) that may interfere with cell functions and ultimately lead to cell death. Researchers are working to determine how mutations in the GRN gene, and the resulting loss of granulin, are related to a buildup of TDP-43 in the brain.
The features of GRN-related frontotemporal dementia result from the gradual loss of neurons in regions near the front of the brain called the frontal and temporal lobes. The frontal lobes are involved in reasoning, planning, judgment, and problem-solving, while the temporal lobes help process hearing, speech, memory, and emotion. The death of neurons in these areas causes problems with many critical brain functions. However, it is unclear why the loss of neurons occurs in the frontal and temporal lobes more often than other brain regions in people with GRN-related frontotemporal dementia.
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Cytogenetic Location: 17q21.31, which is the long (q) arm of chromosome 17 at position 21.31
Molecular Location: base pairs 44,345,086 to 44,353,106 on chromosome 17 (Homo sapiens Updated Annotation Release 109.20190607, GRCh38.p13) (NCBI)
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- acrogranin
- CLN11
- GEP
- GP88
- granulin
- granulin-epithelin
- granulins
- granulins precursor
- GRN_HUMAN
- PC cell-derived growth factor
- PCDGF
- PEPI
- PGRN
- proepithelin
- progranulin
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