ADGRL1-related disorder is an autosomal dominant condition linked to missense, nonsense or frameshift variants in ADGRL1. Most of the mutations are de novo, but inherited variants from affected parents were reported.
ADGRL1 is a member of the adhesion G protein-coupled receptors family (aGPCRs). aGPCRs interact with membrane-bound proteins, extracellular matrix components, or soluble molecules and play a critical role in central nervous system development, synapse formation, myelination, and immunity.
Several laboratories contributed to the untangling of the ADGRL1 interactome, showing its ability to bind a variety of ligands —including teneurin transmembrane protein 2; neurexins 1a, 1b, and 2b; fibronectin leucine-rich transmembrane protein 1 and 3; and contactins— and indicating its major role in regulating synaptic development and activity.
Few studies have directly implicated ADGRLs genes in human pathology, although this subfamily has been previously linked to several psychiatric, neurologic, or neurodevelopmental conditions, such as autism spectrum disorder, attention deficit and hyperactivity disorder, bipolar disorder, schizophrenia, epilepsy, and substance use disorder.
Recently, Vitobello et al. provided functional and molecular data demonstrating that the pathological functions of ADGRL1mutations are consistent with haploinsufficiency and that Adgrl1 deletion in mouse led to impaired synapse formation and activity.
ADGRL1