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Table 2 Mutant CLN genes and underlying pathophysiology of various forms of NCLs

From: Emerging new roles of the lysosome and neuronal ceroid lipofuscinoses

Mutant Gene Cells/ tissues Myoclonus & Seizures Autofluorescent inclusions Elevated lysosomal pH ER Stress Dysregulated degradation Cellular dysfunction
CLN1 Ubiquitously expressed, CNS, brain X X X X X protein response
CLN2 Ubiquitously expressed, brain, neurons, cerebrospinal fluid X X    X Endocytic pathway dysfunction
CLN3 Ubiquitously expressed, CNS, immune and circulatory systems, iPSC, neural progenitor cells, colorectal cancer cells X X X X X TGN is impaired, localized on the lysosome, cellular proliferation, apoptosis and synaptic transmission
CLN4 Ubiquitously expressed, neuronal synapses (1% of total synaptic vesicle-associated proteins) X (Type A) X X Type: B manifests movement abnormalities with dementia
CLN5 Ubiquitously expressed in human tissue, CNS, peripheral organs and tissues, neurons (ganglionic eminence) and microglia X X X    Endosomal sorting, the stability of sortilin and CIMPR both declines, defective myelination
CLN6 Ubiquitously expressed X X   X X manifest characteristic cholesterol and subunit c of mitochondrial ATP synthase (SCMAS), aberrant biometal metabolism
CLN7 Ubiquitously expressed at a very low level, its expression in the liver, heart, and pancreas (markedly higher) X X X   X loss of CLN7 causes depletion of soluble proteins in the lysosomes impairing reactivation of mTOR
CLN8 Ubiquitously expressed, high level expression in cerebral cortex and hippocampus in electrical kindling model of epilepsy X X   X X progressive motor neuron dysfunction and retinal degeneration, lysosomal β-glucosidase deficiency,
CLN9 Currently designated as CLN4  
CLN10 Ubiquitously expressed, brain X X X   X CTSD-processing
CLN11 Ubiquitously expressed, CNS, neuron, microglia, astrocytes, and endothelial cells X X X significantly activated microglia after TBI, the elevated lysosomal biogenesis in activated microglia, which increased cerebrocortical neuron damage, reduces lysosomal biogenesis
CLN12 Ubiquitously expressed, ventral midbrain, including substantia nigra (high lever), kidney and skeletal muscle (low level) X X X extrapyramidal involvement, oxidative-stress in neuroblastoma cells; dysregulated neurotransmission
CLN13 CTSF is expressed at a high level in cerebrocortical, hippocampal and cerebellar neurons X X X neurons showed accumulation of eosinophilic granules
CLN14 Ubiquitously expressed, cerebrocortical and cerebellar Purkinje cells, pyramidal cell layers of the hippocampus (high levels) X X X disrupt KCTD7-Cullin-3 interactions