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

Summary

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

Location:: 13q32.3-q33.1

Exon count:: 48

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	13	NC_000013.11 (101053776..101417179, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	13	NC_060937.1 (100268892..100632422, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	13	NC_000013.10 (101706128..102068859, complement)

Chromosome 13 - NC_000013.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
Structural architecture of the human NALCN channelosome.
Title: Structural architecture of the human NALCN channelosome.
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.
Structure of the human sodium leak channel NALCN.
Title: Structure of the human sodium leak channel NALCN.
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.
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.
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.
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.
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

Associated conditions

Description	Tests
Congenital contractures of the limbs and face, hypotonia, and developmental delay MedGen: C4225398 OMIM: 616266 GeneReviews: Not available	not available
Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 MedGen: C3809454 OMIM: 615419 GeneReviews: Not available	not available

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH28455 (e-PCR)
- UniSTS:88099

SHGC-105265 (e-PCR)
- UniSTS:169273

SHGC-141771 (e-PCR)
- UniSTS:171074

D13S147 (e-PCR)
- UniSTS:41052

D13S147 (e-PCR)
- UniSTS:147299

D13S1282 (e-PCR)
- UniSTS:72561

STS-N40916 (e-PCR)
- UniSTS:69502

SHGC-82188 (e-PCR)
- UniSTS:103090

99-62611 (e-PCR)
- UniSTS:240829

99-62626 (e-PCR)
- UniSTS:240831

RH119839 (e-PCR)
- UniSTS:133584

99-79306 (e-PCR)
- UniSTS:240852

99-79310 (e-PCR)
- UniSTS:240853

99-79311 (e-PCR)
- UniSTS:240854

99-79313 (e-PCR)
- UniSTS:240856

99-79316 (e-PCR)
- UniSTS:240857

99-79322 (e-PCR)
- UniSTS:240858

RH120745 (e-PCR)
- UniSTS:132827

99-79336 (e-PCR)
- UniSTS:240859

99-79338 (e-PCR)
- UniSTS:240860

99-79396 (e-PCR)
- UniSTS:240864

RH48423 (e-PCR)
- UniSTS:14565

99-79431 (e-PCR)
- UniSTS:240881

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

NG_053176.1 RefSeqGene

Range

5699..368431

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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
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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000013.11 Reference GRCh38.p14 Primary Assembly

Range

101053776..101417179 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

A0A976XH31
XM_017020537.2 → XP_016876026.1 sodium leak channel NALCN isoform X4

UniProtKB/TrEMBL

A0A976XH31

Alternate T2T-CHM13v2.0

Genomic

NC_060937.1 Alternate T2T-CHM13v2.0

Range

100268892..100632422 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

A0A976XH31
XM_054374416.1 → XP_054230391.1 sodium leak channel NALCN isoform X5

UniProtKB/TrEMBL

A0A976XH31
XM_054374413.1 → XP_054230388.1 sodium leak channel NALCN isoform X2

UniProtKB/TrEMBL

A0A976XH31
XM_054374414.1 → XP_054230389.1 sodium leak channel NALCN isoform X3

UniProtKB/TrEMBL

A0A976XH31
XM_054374415.1 → XP_054230390.1 sodium leak channel NALCN isoform X4

UniProtKB/TrEMBL

A0A976XH31