ABOUT THE GRIN2B GENE
GRIN2B is a gene located on the short arm (called “p”) of the 12th chromosome at 12p13.1. It is one member of a family of 7 genes, GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRIN3A, and GRIN3B. These genes encode proteins that together form a receptor that is responsible for sending chemical messages between neurons in the brain. Since there is currently no known “syndrome” name associated with variances of GRIN2B, when referring to “GRIN2B” on this page, we are referring to those individuals with variations or deletions on that specific gene.
GRIN2B stands for: Glutamate Receptor, Ionotropic, N-Methyl D-Aspartate 2B
Genomic location: Chromosome 12 at 12p13.1
Alternate gene names: NMDAR2B, NR2B
Associated syndromes or conditions: Epileptic encephalopathy, early infantile, 27; Intellectual disability type 6 (formerly called “mental retardation type 6”)
This neurological condition is often characterized by low muscle tone, developmental delays, seizures and lack of speech. The spectrum of abilities is quite broad depending on the exact genetic variation. Some of our children cannot walk or talk, and most struggle to communicate their most basic daily needs. It is possible for parents to be carriers, but most cases of GRIN2B are non-inherited (de novo) and have no family history. Those with the mutation are autosomal dominant, meaning they have a 50% chance of passing on the mutation to any offspring.
The following infographic data was gathered from a Spring 2016 survey conducted in the GRIN2B Parent Support Facebook Group.
What is the function of the GRIN2B Gene?
In its normal state, GRIN2B is one component of a receptor that relays signals in the central nervous system (e.g. from cell-to-cell in the brain). These receptors are called NMDA receptors. These receptors can be turned on/off. It is likely that these receptors turn on/off thousands of times every day as signals are sent and received in the brain. This is normal. They are turned on when a molecule called glutamate binds to them. Think of a key in a lock to open a door. When the door is closed and locked (called the resting state), the receptor is off and blocked by a kind of electric current (magnesium ions). No signal gets through the closed door. When the glutamate binds, it is like unlocking the door. This turns off the magnesium blockade and turns on the receptor (called the active state). This allows calcium ions to flow through the open door, which transmit signals to the nerve cells of the brain.
Where there is a change in the GRIN2B gene, it will be classified as either a gain-of-function or loss-of-function mutation.
In a gain-of-function mutation, the receptor is more active than normal. This means it is turned on too much of the time, or that the signals are too strong. This can impact how well the brain receives signals and leads to neurodevelopmental problems. Too much signal can over-excite the brain, which impacts how connections are made and might* result in seizures.
*There are some children with a gain-of-function mutation that have not shown any seizure activity so far.
LOSS OF FUNCTION:
In a loss-of-function mutation, the receptor is less active than normal. This means that it is turned off too much of the time, or that the signal is too weak. This can also impact how well the brain receives signals and leads to neurodevelopmental problems. Too little signal might limit communication across the brain, which can limit the number of connections and might result in learning difficulties.