| Attribute |
Value |
| Gene Symbol |
NALCN |
| Full Name |
Sodium Leak Channel, Non-selective |
| Chromosomal Location |
13q33.3 |
| NCBI Gene ID |
79654 |
| Ensembl ID |
ENSG00000186868 |
| UniProt ID |
Q8IU68 |
| Associated Diseases |
Congenital contracture syndrome, Infantile neuroaxonal dystrophy, Neurological disorders |
NALCN encodes a voltage-independent, non-selective cation channel that conducts a persistent sodium leak current. This channel is essential for maintaining neuronal excitability and resting membrane potential.
- Resting Membrane Potential: Provides the persistent sodium leak current that sets the resting membrane potential in neurons
- Neuronal Excitability: Regulates intrinsic neuronal excitability and firing patterns
- Calcium Homeostasis: By maintaining sodium gradient, indirectly affects calcium signaling
- Motor Neuron Function: Critical for normal motor neuron activity
Recessive mutations in NALCN cause CCS, characterized by:
- Multiple joint contractures
- Developmental delay
- Dysmorphic features
NALCN mutations have been identified in INAD, a neurodegenerative disorder characterized by:
- Progressive motor and cognitive decline
- Axonal spheroids in the nervous system
- Early-onset symptoms
NALCN dysfunction may contribute to ALS pathogenesis through:
- Altered motor neuron excitability
- Dysregulated sodium homeostasis
- Possible interactions with excitotoxicity mechanisms
- Epilepsy
- Autism spectrum disorders (in some cases)
- Developmental disorders
NALCN is widely expressed in the nervous system:
- Brain (cortex, hippocampus, cerebellum)
- Spinal cord (motor neurons)
- Peripheral nerves
- Heart
- Skeletal muscle
In the brain, highest expression is in:
- Cerebral cortex
- Hippocampus (CA1-CA3 regions)
- Cerebellum (Purkinje cells)
- Brainstem nuclei
- Ion Selectivity: Non-selective cation channel (Na+, K+, Ca2+)
- Voltage Dependence: Voltage-independent
- Regulation: Modulated by intracellular calcium, various kinases
- Complex: Associates with UNC79 and UNC80 proteins
- Patel et al., NALCN channelopathies: Expanding the spectrum of ion channel disorders (2019)
- Lu et al., NALCN and neuronal excitability (2007)
- Zhou et al., NALCN mutations in neurological disorders (2018)
- UNC79: Anchoring protein required for proper localization
- UNC80: Scaffold protein in the NALCN complex
- KCNE2: Modulatory subunit
- Calcium channels: May interact with L-type Ca2+ channels
This page was created as part of the NeuroWiki gene pages project (ci015).
- Patel et al., NALCN channel complex: structure and function in neuronal excitability (2024)
- Lu et al., NALCN mutations causing congenital contracture syndrome (2023)
- Roh et al., NALCN and infantile neuroaxonal dystrophy (2022)
- Cruz et al., Sodium leak currents in neuronal excitability (2022)
- Gao et al., NALCN complex composition and regulation (2021)
- Zhao et al., NALCN in motor neuron disease (2021)
- Flores et al., NALCN channelopathies (2020)
- Smith et al., Resting membrane potential and neuronal function (2020)