NALCN

Chr 13

sodium leak channel, non-selective

Also known as: CLIFAHDD, CanIon, IHPRF, IHPRF1, INNFD, VGCNL1, bA430M15.1

NCBI Gene: 259232ENSG00000102452UniProt: Q8IZF0

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]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHypotonia, infantile, with psychomotor retardation and characteristic facies 1
UniProtCongenital contractures of the limbs and face, hypotonia, and developmental delay

Clinical highlights

Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
37
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.52
LOEUF
LOF*
Mechanism· G2P
📖
GeneReview available — NALCN
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?
0.52LOEUF
pLI 0.000
Z-score 5.59
OE 0.40 (0.31–0.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
4.96Z-score
OE missense 0.56 (0.52–0.60)
563 obs / 1005.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.40 (0.31–0.52)
0≤0.351.4
Missense OE?0.56 (0.52–0.60)
0≤0.61.4
Synonymous OE?0.99
0≤1.21.6
LoF obs/exp: 41 / 101.9Missense obs/exp: 563 / 1005.1Syn Z: 0.13

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

NALCN · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients