RAB3GAP2

At least 10 RAB3GAP2 gene mutations have been found to cause RAB18 deficiency, resulting in conditions that affect the eyes, brain, and reproductive system. The two conditions caused by this deficiency are Warburg micro syndrome at the severe end of the spectrum and Martsolf syndrome at the mild end. RAB3GAP2 gene mutations are the most common cause of Martsolf syndrome and can also cause Warburg micro syndrome.

Martsolf syndrome is caused by RAB3GAP2 gene mutations that reduce the amount of functional RAB3GAP2 protein. Warburg micro syndrome occurs when the gene mutations prevent the production of any RAB3GAP2 protein or completely eliminate its function. Reduction or loss of this protein likely impairs the formation or function of the RAB3GAP complex, leading to a shortage (deficiency) of RAB18 activity. It is unclear why the loss of RAB18 function leads to eye problems, brain abnormalities, and other features of these two conditions.

Because Warburg micro syndrome and Martsolf syndrome can be caused by mutations in other genes that disrupt normal RAB18 activity, loss of control of this GTPase is thought to underlie the conditions. It is unclear if impaired regulation of RAB3 activity contributes to the features of Warburg micro syndrome or Martsolf syndrome.

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