Biallelic mutations in ELFN1 gene associated with developmental and epileptic encephalopathy and joint laxity

Complex N-glycosylation of mGluR6 is required for trans-synaptic interaction with ELFN adhesion proteins

“…Similarly, ELFN1 and ELFN2 interact with and allosterically modulate other group III mGluRs—mGluR4, mGluR7, and mGluR8—affecting synapse function in the brain ( 8 , 9 , 10 , 11 , 12 ). Consistent with this, mutations in the ELFN1 gene have been associated with neurological and psychiatric disorders ( 10 , 13 , 14 , 15 ). With the exception of mGluR6, the group III mGluRs are typically located in presynaptic membranes, where they influence glutamate release and interact with postsynaptic ELFN proteins ( 10 , 11 , 16 , 17 ).…”

Genomic analysis identifies risk factors in restless legs syndrome

“…Our TWAS showed that increased expression of ELFN1 (in cis with 7p22.3 locus) is associated with RLS. ELFN1 has relevant implications in the brain 65,66 and is associated with several neuropsychiatric and neurodevelopmental disorders, including intellectual disability, attention deficit hyperactivity disorder, and epilepsy 66-68 . Elfn1 protein has been shown to play a role in the modulation of synaptic transmission through its trans interaction with the metabotropic glutamate receptors 69 , which serve as therapeutic targets for several neurological diseases, including Alzheimer’s disease, epilepsy, and Parkinson’s disease 70-72 .…”

Variability in Neural Circuit Formation

“…) Most of these conditions are recessive, meaning both copies of the gene must be mutated to cause the phenotype (as is commonly observed for axon guidance genes in model organisms). Such conditions are therefore very rare and have usually been identified in consanguineous populations (e.g., for ELFN1 gene; Dursun et al 2021). However, while this is true of complete loss-of-function mutations, mutations that result in a truncated protein (especially for transmembrane receptors) can often have dominant effects.…”