EFNB1 is located on Xq13.1 and is composed of five exons.
EFNB1 encodes Ephrin-B1 which is a type I membrane protein and member of the ephrin superfamily of transmembrane ligands for Eph receptor tyrosine kinases (RKT), has a of 346 amino acids with a mass of 38 KDa. These proteins allow short distance cell-cell communication which activates direct signaling pathways affecting cell repulsion or cell adhesion on the cellular cytoskeleton, therefore they take part on the cellular migration and morphology in the developmental process of the embryo. In mice, the Efnb1 gene is known to be highly expressed in the frontonasal neural crest and might explain the cranial and extracranial midline defects.
Mutations in EFNB1 gene predict a complete or partial loss of Ephrin-B1 function. Whether they are missense, nonsense, frameshift or even deletions, they all cause loss of function in the protein.
As the EFNB1 gene is located on the X chromosome and thus, it is an X-linked disorder, which paradoxically show a more severe phenotype on heterozygous females than in hemizygous males. The occurrence of this paradox might be explained by the interaction of a random X-inactivation in females and the cellular interference mechanism, which means that the interaction of a mutant and a normal allele lead to a more severe phenotype than the mutant allele alone. Therefore, we could summarize the mechanism underlying the paradox as follows:
1. Random X-inactivation in females.
2. Abnormal cellular interactions due to the mosaic state of females.
3. Functional redundancy of the gene in the non-mosaic hemizygous males.
EFNB1