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NALCN sodium leak channel, non-selective [ Homo sapiens (human) ]

Gene ID: 259232, updated on 3-Apr-2024

Summary

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Official Symbol
NALCNprovided by HGNC
Official Full Name
sodium leak channel, non-selectiveprovided by HGNC
Primary source
HGNC:HGNC:19082
See related
Ensembl:ENSG00000102452 MIM:611549; AllianceGenome:HGNC:19082
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
IHPRF; INNFD; CanIon; IHPRF1; VGCNL1; CLIFAHDD; bA430M15.1
Summary
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]
Expression
Biased expression in brain (RPKM 11.1), adrenal (RPKM 2.5) and 5 other tissues See more
Orthologs
mouse all
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Genomic context

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Location:
13q32.3-q33.1
Exon count:
48
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (101053776..101417179, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (100268892..100632422, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (101706128..102068859, complement)

Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene NALCN antisense RNA 1 Neighboring gene Sharpr-MPRA regulatory region 9290 Neighboring gene ADP ribosylation factor 4 pseudogene 3 Neighboring gene long intergenic non-protein coding RNA 411 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:101698875-101699376 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr13:101701141-101702340 Neighboring gene uncharacterized LOC124903202 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:101717146-101717646 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:101717647-101718147 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr13:101909917-101911116 Neighboring gene NANOG hESC enhancer GRCh37_chr13:101986545-101987100 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:102068211-102068761 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:102067660-102068210 Neighboring gene Sharpr-MPRA regulatory region 15039 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr13:102102071-102103270 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:102104604-102105108 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:102126208-102126708 Neighboring gene Sharpr-MPRA regulatory region 3234 Neighboring gene integrin subunit beta like 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr13:102341159-102341390 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr13:102360299-102360823 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7963 Neighboring gene NANOG hESC enhancer GRCh37_chr13:102403785-102404286 Neighboring gene fibroblast growth factor 14 Neighboring gene RNA, U1 small nuclear 24, pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Case Report: A de novo Variant in NALCN Associated With CLIFAHDD Syndrome in a Chinese Infant. Liao Z, et al. Front Pediatr, 2022. PMID 35911839, Free PMC Article
  2. Structural architecture of the human NALCN channelosome. Kschonsak M, et al. Nature, 2022 Mar. PMID 34929720
  3. A homozygous truncating NALCN variant in two Afro-Caribbean siblings with hypotonia and dolichocephaly. Ope O, et al. Am J Med Genet A, 2020 Aug. PMID 32618095
  4. Functional expression of CLIFAHDD and IHPRF pathogenic variants of the NALCN channel in neuronal cells reveals both gain- and loss-of-function properties. Bouasse M, et al. Sci Rep, 2019 Aug 13. PMID 31409833, Free PMC Article
  5. Periodic breathing in patients with NALCN mutations. Bourque DK, et al. J Hum Genet, 2018 Oct. PMID 29968795

See all (55) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. New insights into the physiology and pathophysiology of the atypical sodium leak channel NALCN.
    Title: New insights into the physiology and pathophysiology of the atypical sodium leak channel NALCN.
  2. Extending and outlining the genotypic and phenotypic spectrum of novel mutations of NALCN gene in IHPRF1 syndrome: identifying recurrent urinary tract infection.
    Title: Extending and outlining the genotypic and phenotypic spectrum of novel mutations of NALCN gene in IHPRF1 syndrome: identifying recurrent urinary tract infection.
  3. Structural architecture of the human NALCN channelosome.
    Title: Structural architecture of the human NALCN channelosome.
  4. A homozygous truncating NALCN variant in two Afro-Caribbean siblings with hypotonia and dolichocephaly.
    Title: A homozygous truncating NALCN variant in two Afro-Caribbean siblings with hypotonia and dolichocephaly.
  5. Structure of the human sodium leak channel NALCN.
    Title: Structure of the human sodium leak channel NALCN.
  6. Structure of the human sodium leak channel NALCN in complex with FAM155A.
    Title: Structure of the human sodium leak channel NALCN in complex with FAM155A.
  7. Functional expression of CLIFAHDD and IHPRF pathogenic variants of the NALCN channel in neuronal cells reveals both gain- and loss-of-function properties.
    Title: Functional expression of CLIFAHDD and IHPRF pathogenic variants of the NALCN channel in neuronal cells reveals both gain- and loss-of-function properties.
  8. Intellectual disability-associated UNC80 mutations reveal inter-subunit interaction and dendritic function of the NALCN channel complex.
    Title: Intellectual disability-associated UNC80 mutations reveal inter-subunit interaction and dendritic function of the NALCN channel complex.
  9. PRMT7-mediated NALCN inhibition provides a potential target for the development of therapeutic tools for neurological diseases
    Title: Methylation determines the extracellular calcium sensitivity of the leak channel NALCN in hippocampal dentate granule cells.
  10. these are the first European cases with Infantile hypotonia with psychomotor retardation and characteristic facies-1 syndrome with biallelic truncating mutations of NALCN.
    Title: Novel NALCN biallelic truncating mutations in siblings with IHPRF1 syndrome.
Submit: New GeneRIF Correction See all GeneRIFs (30)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder.
EBI GWAS Catalog
Genome-wide association study of atypical psychosis.
EBI GWAS Catalog
Genome-wide association study of neurocognitive impairment and dementia in HIV-infected adults.
EBI GWAS Catalog
Prognostic implications of genetic variants in advanced non-small cell lung cancer: a genome-wide association study.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ23913, FLJ44659, FLJ44764, MGC74524

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables leak channel activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables monoatomic cation channel activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables monoatomic cation channel activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables sodium channel activity TAS
Traceable Author Statement
more info
  
enables voltage-gated sodium channel activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables voltage-gated sodium channel activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
involved_in calcium ion transmembrane transport ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in monoatomic ion transmembrane transport TAS
Traceable Author Statement
more info
  
involved_in positive regulation of synaptic transmission, GABAergic IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of synaptic transmission, cholinergic IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in potassium ion transmembrane transport ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of resting membrane potential ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in sodium ion transmembrane transport ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
part_of monoatomic ion channel complex IEA
Inferred from Electronic Annotation
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
sodium leak channel NALCN
Names
four repeat voltage-gated ion channel
voltage gated channel like 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_053176.1 RefSeqGene

    Range
    5699..368431
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001350748.2 → NP_001337677.1  sodium leak channel NALCN isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AL138707, AL354891, AL356778, BF516239, KF511189
    Consensus CDS
    CCDS91832.1
    UniProtKB/TrEMBL
    A0A6Q8PFS9, A0A976XH31
    Related
    ENSP00000501955.1, ENST00000675332.1
    Conserved Domains (1) summary
    pfam00520
    Location:916 → 1190
    Ion_trans; Ion transport protein

  2. NM_001350749.2 → NP_001337678.1  sodium leak channel NALCN isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate splice site in the 5' UTR and lacks an alternate exon in the 5' coding region but maintains the reading frame, compared to variant 1. The encoded isoform (2) is shorter than isoform 1. Both variants 2 and 3 encode the same isoform (2).
    Source sequence(s)
    AL138707, AL354891, AL356778, BF516239, KF511189
    Consensus CDS
    CCDS9498.1
    UniProtKB/Swiss-Prot
    Q6P2S6, Q6ZMI7, Q8IZF0, Q8IZZ1, Q8TAH1
    UniProtKB/TrEMBL
    A0A976XH31
    Conserved Domains (1) summary
    pfam00520
    Location:887 → 1161
    Ion_trans; Ion transport protein

  3. NM_001350750.2 → NP_001337679.1  sodium leak channel NALCN isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks two alternate exons in the 5' coding region but maintains the reading frame, compared to variant 1. The encoded isoform (3) is shorter than isoform 1. Both variants 4 and 5 encode the same isoform (3).
    Source sequence(s)
    AL138707, AL354891, AL356778, BF516239, KF511189
    Consensus CDS
    CCDS91831.1
    UniProtKB/TrEMBL
    A0A6Q8PF19, A0A976XH31
    Related
    ENSP00000501603.1, ENST00000676315.1
    Conserved Domains (1) summary
    pfam00520
    Location:858 → 1132
    Ion_trans; Ion transport protein

  4. NM_001350751.2 → NP_001337680.1  sodium leak channel NALCN isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) uses an alternate splice site in the 5' UTR and lacks two alternate exons in the 5' coding region but maintains the reading frame, compared to variant 1. The encoded isoform (3) is shorter than isoform 1. Both variants 4 and 5 encode the same isoform (3).
    Source sequence(s)
    AL138707, AL354891, AL356778, BF516239, KF511189
    Consensus CDS
    CCDS91831.1
    UniProtKB/TrEMBL
    A0A6Q8PF19, A0A976XH31
    Conserved Domains (1) summary
    pfam00520
    Location:858 → 1132
    Ion_trans; Ion transport protein

  5. NM_052867.4 → NP_443099.1  sodium leak channel NALCN isoform 2

    See identical proteins and their annotated locations for NP_443099.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate exon in the 5' coding region but maintains the reading frame, compared to variant 1. The encoded isoform (2) is shorter than isoform 1. Both variants 2 and 3 encode the same isoform (2).
    Source sequence(s)
    AK002089, AL356778, AY141972, BC012128, BF516239, DA128114
    Consensus CDS
    CCDS9498.1
    UniProtKB/Swiss-Prot
    Q6P2S6, Q6ZMI7, Q8IZF0, Q8IZZ1, Q8TAH1
    UniProtKB/TrEMBL
    A0A976XH31
    Related
    ENSP00000251127.6, ENST00000251127.11
    Conserved Domains (1) summary
    pfam00520
    Location:887 → 1161
    Ion_trans; Ion transport protein

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000013.11 Reference GRCh38.p14 Primary Assembly

    Range
    101053776..101417179 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011521069.3 → XP_011519371.1  sodium leak channel NALCN isoform X2

    UniProtKB/TrEMBL
    A0A976XH31
    Conserved Domains (2) summary
    pfam00520
    Location:1224 → 1448
    Ion_trans; Ion transport protein
    pfam10688
    Location:1256 → 1401
    Imp-YgjV; Bacterial inner membrane protein

  2. XM_011521067.3 → XP_011519369.1  sodium leak channel NALCN isoform X1

    UniProtKB/TrEMBL
    A0A976XH31
    Conserved Domains (2) summary
    pfam00520
    Location:1253 → 1477
    Ion_trans; Ion transport protein
    pfam10688
    Location:1285 → 1430
    Imp-YgjV; Bacterial inner membrane protein

  3. XM_024449336.2 → XP_024305104.1  sodium leak channel NALCN isoform X5

    UniProtKB/TrEMBL
    A0A976XH31
    Conserved Domains (1) summary
    pfam00520
    Location:935 → 1209
    Ion_trans; Ion transport protein

  4. XM_017020536.3 → XP_016876025.1  sodium leak channel NALCN isoform X3

    UniProtKB/TrEMBL
    A0A976XH31

  5. XM_017020537.2 → XP_016876026.1  sodium leak channel NALCN isoform X4

    UniProtKB/TrEMBL
    A0A976XH31

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060937.1 Alternate T2T-CHM13v2.0

    Range
    100268892..100632422 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054374412.1 → XP_054230387.1  sodium leak channel NALCN isoform X1

  2. XM_054374416.1 → XP_054230391.1  sodium leak channel NALCN isoform X5

  3. XM_054374413.1 → XP_054230388.1  sodium leak channel NALCN isoform X2

  4. XM_054374414.1 → XP_054230389.1  sodium leak channel NALCN isoform X3

  5. XM_054374415.1 → XP_054230390.1  sodium leak channel NALCN isoform X4

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8IZF0.1 GenPept UniProtKB/Swiss-Prot:Q8IZF0

Gene LinkOut

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