Table 1

Molecular characteristics of LGI1, CASPR2, and associated proteins

Molecular evidenceLGI1CASPR2ADAM22/23Contactin-2
Genetic mutationsAutosomal dominant partial epilepsy with auditory features10 Homozygous mutations cause epilepsy, intellectual disability and autism11 Heterozygous mutations cause early infantile epileptic encephalopathy with cortical atrophy12 Homozygous mutations cause autosomal recessive familial cortical myoclonic tremor and epilepsy13
Neural expressionCentral nervous system (CNS): strongly expressed within mossy fibre CA3 layer of hippocampus and cerebellum;
Peripheral nervous system (PNS): more weakly expressed8
CNS: stratum radiatum of CA3 layer of hippocampus and cerebellum;
PNS: juxtaparanodes of myelinated axons8
CNS: ADAM22 predominantly within the cerebellum, hippocampus, amygdala, and cerebral cortex; ADAM 23 hypothalamus and thalamus.14 Both are also expressed in the PNSCNS: cerebellum, CA1 and CA3 hippocampal pyramidal cells, olfactory bulb, white matter tracts;15
PNS: juxtaparanodes of myelinated axons16
Interacting proteinsBinds to pre-synaptic ADAM23 and post-synaptic ADAM22,17 with some evidence for ADAM11;18
Associates closely with Kv1.1 channels pre-synaptically and AMPARs post-synaptically19–21
Contactin-2,8 16 via EGF2 and laminin G4 domains of CASPR222 LGI1,17 and closely related LGI1 family moleculesCASPR28 16 via Ig and fibronectin domains of contactin-222
  • ADAM, a disintegrin and metalloprotease; AMPARs, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors; CASPR2, contactin-associated protein like-2; EGF2, epidermal growth factor-2; LGI1, leucine-rich glioma-inactivated 1.