NALCN

Chr 13q32.3-q33.1

sodium leak channel, non-selective

Aliases:: bA430M15.1, CanIon
MANE:: ENST00000251127.11

OMIM: 611549 ↗NCBI: 259232 ↗Ensembl ↗

Annotations refreshed 10 hours ago.

Predicted protein structure

AlphaFold predicted structure

NALCN · Q8IZF0

v62025-08-01

Predicted Aligned Error matrix for NALCN — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

76.7/ 100

Confident

1,738 residues

Confidence breakdown

Very high(≥ 90)45%
Confident(70–90)29%
Low(50–70)7%
Very low(< 50)20%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Arthrogryposis
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
DDG2P
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Disease associations (Open Targets)

congenital contractures of the limbs and face, hypotonia, and developmental delay
0.82
hypotonia, infantile, with psychomotor retardation and characteristic facies 1
0.79
hereditary disease
0.54
hypotonia, infantile, with psychomotor retardation and characteristic facies
0.48
Abnormality of the nervous system
0.44
Intellectual disability
0.39
Freeman-Sheldon syndrome
0.37
digitotalar dysmorphism
0.37
Sheldon-hall syndrome
0.37
arthrogryposis multiplex congenita
0.36

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Sodium leak channel NALCN

Voltage-sensing, pore-forming subunit of the NALCN channelosome complex, which regulates the resting membrane potential by depolarizing sodium leak currents (PubMed:17448995, PubMed:32494638, PubMed:33203861, PubMed:35387979, PubMed:34929720). The NALCN channelosome complex is a voltage-gated ion channel responsible for the resting Na(+) permeability that controls neuronal excitability (PubMed:17448995, PubMed:31409833, PubMed:35387979, PubMed:34929720). The NALCN channelosome 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). The NALCN channelosome 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)