NALCN

This gene encodes a voltage-independent, nonselective cation channel which belongs to a family of voltage-gated sodium and calcium channels that regulates the resting membrane potential and excitability of neurons. This family is expressed throughout the nervous system and conducts a persistent sodium leak current that contributes to tonic neuronal excitability. The encoded protein forms a channelosome complex that includes G-protein-coupled receptors, UNC-79, UNC-80, NCA localization factor-1, and src family tyrosine kinases. Naturally occurring mutations in this gene are associated with infantile neuroaxonal dystrophy, infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) syndrome, and congenital contractures of the limbs and face with hypotonia and developmental delay (CLIFAHDD) syndrome. A knockout of the orthologous gene in mice results in paralysis with a severely disrupted respiratory rhythm, and lethality within 24 hours after birth. [provided by RefSeq, Apr 2017]

Sodium Leak Channel, Non-Selective

Voltage-gated ion channel responsible for the resting Na+ permeability that controls neuronal excitability (PubMed:17448995, PubMed:31409833).

NALCN channel functions as a multi-protein complex, which consists at least of NALCN, NALF1, UNC79 and UNC80 (PubMed:32494638, PubMed:33203861).

NALCN is the voltage-sensing, pore-forming subunit of the NALCN channel complex (PubMed:17448995).

NALCN channel complex is constitutively active and conducts monovalent cations but is blocked by physiological concentrations of extracellular divalent cations (PubMed:32494638).

In addition to its role in regulating neuronal excitability, is required for normal respiratory rhythm, systemic osmoregulation by controlling the serum sodium concentration and in the regulation of the intestinal pace-making activity in the interstitial cells of Cajal (By similarity).

NALCN channel is also activated by neuropeptides such as neurotensin and substance P (SP) through a SRC family kinases-dependent pathway (By similarity).

In addition, NALCN activity is enhanced/modulated by several GPCRs, such as CHRM3 (By similarity).

Calcium ion transmembrane transport Source: UniProtKB
Ion transmembrane transport Source: Reactome
Potassium ion transmembrane transport Source: UniProtKB
Regulation of ion transmembrane transport Source: UniProtKB-KW
Regulation of resting membrane potential Source: UniProtKB
Sodium ion transmembrane transport Source: UniProtKB

Cell membrane

Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 (IHPRF1):
A neurodegenerative disease characterized by variable degrees of hypotonia, speech impairment, intellectual disability, pyramidal signs, subtle facial dysmorphism, and chronic constipation. Some patients manifest neuroaxonal dystrophy, optic atrophy, unmyelinated axons and spheroid bodies in tissue biopsies.
Congenital contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD):
A disease characterized by congenital contractures of the limbs and face, resulting in characteristic facial features, abnormal tone, most commonly manifested as hypotonia, and variable degrees of developmental delay.

Cytoplasmic: 1-36
Helical: 37-57
Extracellular: 58-65
Helical: 66-90
Cytoplasmic: 91-106
Helical: 107-129
Extracellular: 130-137
Helical: 138-158
Cytoplasmic: 159-173
Helical: 174-199
Extracellular: 200-269
Helical: 270-289
Cytoplasmic: 290-294
Helical: 295-322
Extracellular: 323-382
Helical: 383-403
Cytoplasmic: 404-416
Helical: 417-439
Extracellular: 440-447
Helical: 448-468
Cytoplasmic: 469-472
Helical: 473-492
Extracellular: 493-502
Helical: 503-530
Cytoplasmic: 531-543
Pore-forming: 544-563
Extracellular: 564-569
Helical: 570-599
Cytoplasmic: 600-886
Helical: 887-906
Extracellular: 907-915
Helical: 916-939
Cytoplasmic: 940-947
Helical: 948-972
Extracellular: 973-980
Helical: 981-1003
Cytoplasmic: 1004-1015
Helical: 1016-1039
Extracellular: 1040-1104
Pore-forming: 1105-1124
Cytoplasmic: 1125-1129
Helical: 1130-1159
Extracellular: 1160-1210
Helical: 1211-1227
Cytoplasmic: 1228-1236
Helical: 1237-1260
Extracellular: 1261-1271
Helical: 1272-1293
Cytoplasmic: 1294-1296
Helical: 1297-1318
Extracellular: 1319-1331
Helical: 1332-1357
Cytoplasmic: 1358-1378
Pore-forming: 1379-1398
Extracellular: 1399-1420
Helical: 1421-1447
Cytoplasmic: 1448-1738

Phosphorylated on tyrosine residues.