To date we have observed two homozygous causes of disease. One arising from a canonical splice site variant, the second occurring due to a homozygous missense variant. COPB1 is a subunit of coatomer complex one, a group of proteins involved in the endomembrane system which traffic proteins from the Golgi apparatus back to the endoplasmic reticulum. Functional work suggests that variants may adversely affect this function with poor localisation of the protein occurring. The suggested mechanism of disease is a partial loss of function from hypomorphic variants. Animal modelling in Xenopus tropicalis suggests full loss of function is likely to be embryonic lethal.
Early exploratory work suggests a distinct disease may occur due to heterozygous variants, though this is not yet fully established.
COPB1