NALCN

Protein identityUniProt · HPA

UniProt accession

Q8IZF0

Gene

NALCN

Ensembl

ENSG00000102452

Chromosome

13

Canonical length

1738 aa

Protein class

Disease related genes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

Subcellular location

Nucleoli,Plasma membrane,Microtubules,Cytokinetic bridge,Mitotic spindle,Primary cilium,Cytosol

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1738 residues, UniProt reviewed canonical sequence.

>Q8IZF0|NALCN
     1  MLKRKQSSRV EAQPVTDFGP DESLSDNADI LWINKPWVHS LLRICAIISV ISVCMNTPMT
    61  FEHYPPLQYV TFTLDTLLMF LYTAEMIAKM HIRGIVKGDS SYVKDRWCVF DGFMVFCLWV
   121  SLVLQVFEIA DIVDQMSPWG MLRIPRPLIM IRAFRIYFRF ELPRTRITNI LKRSGEQIWS
   181  VSIFLLFFLL LYGILGVQMF GTFTYHCVVN DTKPGNVTWN SLAIPDTHCS PELEEGYQCP
   241  PGFKCMDLED LGLSRQELGY SGFNEIGTSI FTVYEAASQE GWVFLMYRAI DSFPRWRSYF
   301  YFITLIFFLA WLVKNVFIAV IIETFAEIRV QFQQMWGSRS STTSTATTQM FHEDAAGGWQ
   361  LVAVDVNKPQ GRAPACLQKM MRSSVFHMFI LSMVTVDVIV AASNYYKGEN FRRQYDEFYL
   421  AEVAFTVLFD LEALLKIWCL GFTGYISSSL HKFELLLVIG TTLHVYPDLY HSQFTYFQVL
   481  RVVRLIKISP ALEDFVYKIF GPGKKLGSLV VFTASLLIVM SAISLQMFCF VEELDRFTTF
   541  PRAFMSMFQI LTQEGWVDVM DQTLNAVGHM WAPVVAIYFI LYHLFATLIL LSLFVAVILD
   601  NLELDEDLKK LKQLKQSEAN ADTKEKLPLR LRIFEKFPNR PQMVKISKLP SDFTVPKIRE
   661  SFMKQFIDRQ QQDTCCLLRS LPTTSSSSCD HSKRSAIEDN KYIDQKLRKS VFSIRARNLL
   721  EKETAVTKIL RACTRQRMLS GSFEGQPAKE RSILSVQHHI RQERRSLRHG SNSQRISRGK
   781  SLETLTQDHS NTVRYRNAQR EDSEIKMIQE KKEQAEMKRK VQEEELRENH PYFDKPLFIV
   841  GREHRFRNFC RVVVRARFNA SKTDPVTGAV KNTKYHQLYD LLGLVTYLDW VMIIVTICSC
   901  ISMMFESPFR RVMHAPTLQI AEYVFVIFMS IELNLKIMAD GLFFTPTAVI RDFGGVMDIF
   961  IYLVSLIFLC WMPQNVPAES GAQLLMVLRC LRPLRIFKLV PQMRKVVREL FSGFKEIFLV
  1021  SILLLTLMLV FASFGVQLFA GKLAKCNDPN IIRREDCNGI FRINVSVSKN LNLKLRPGEK
  1081  KPGFWVPRVW ANPRNFNFDN VGNAMLALFE VLSLKGWVEV RDVIIHRVGP IHGIYIHVFV
  1141  FLGCMIGLTL FVGVVIANFN ENKGTALLTV DQRRWEDLKS RLKIAQPLHL PPRPDNDGFR
  1201  AKMYDITQHP FFKRTIALLV LAQSVLLSVK WDVEDPVTVP LATMSVVFTF IFVLEVTMKI
  1261  IAMSPAGFWQ SRRNRYDLLV TSLGVVWVVL HFALLNAYTY MMGACVIVFR FFSICGKHVT
  1321  LKMLLLTVVV SMYKSFFIIV GMFLLLLCYA FAGVVLFGTV KYGENINRHA NFSSAGKAIT
  1381  VLFRIVTGED WNKIMHDCMV QPPFCTPDEF TYWATDCGNY AGALMYFCSF YVIIAYIMLN
  1441  LLVAIIVENF SLFYSTEEDQ LLSYNDLRHF QIIWNMVDDK REGVIPTFRV KFLLRLLRGR
  1501  LEVDLDKDKL LFKHMCYEME RLHNGGDVTF HDVLSMLSYR SVDIRKSLQL EELLAREQLE
  1561  YTIEEEVAKQ TIRMWLKKCL KRIRAKQQQS CSIIHSLRES QQQELSRFLN PPSIETTQPS
  1621  EDTNANSQDN SMQPETSSQQ QLLSPTLSDR GGSRQDAADA GKPQRKFGQW RLPSAPKPIS
  1681  HSVSSVNLRF GGRTTMKSVV CKMNPMTDAA SCGSEVKKWW TRQLTVESDE SGDDLLDI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NALCN can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

24

Mean surface accessibility (rSASA)

0.33

Highest tissue expression

15 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NALCN.

Disease | AllUniProt

Conditions NALCN is implicated in, by any mechanism.

• Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 (IHPRF1) MIM:615419
• Congenital contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD) MIM:616266

Disease | GeneticClinVar

180 pathogenic / likely-pathogenic of 1,367 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Congenital contractures of the limbs and face, hypotonia, and developmental delay
• Hypotonia, infantile, with psychomotor retardation and characteristic facies 1
• Inborn genetic diseases
• NALCN-related disorder
• Fetal akinesia deformation sequence 1

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.52

gnomAD pLI

0

gnomAD missense Z

4.96

DepMap mean gene effect

0.06

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• calcium ion transmembrane transport
• monoatomic ion transmembrane transport
• positive regulation of synaptic transmission, cholinergic
• positive regulation of synaptic transmission, GABAergic
• potassium ion transmembrane transport
• regulation of resting membrane potential
• sodium ion transmembrane transport

Molecular functions

• leak channel activity
• monoatomic cation channel activity
• sodium channel activity
• voltage-gated sodium channel activity

Cellular components

• monoatomic ion channel complex
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Ion transport domain
• Voltage-dependent channel domain superfamily
• Ion transport protein
• Sodium leak channel NALCN

KeywordsUniProt

• Cell membrane
• Coiled coil
• Disulfide bond
• Glycoprotein
• Ion channel
• Ion transport
• Membrane
• Neurodegeneration
• Repeat
• Sodium
• Sodium channel
• Sodium transport
• Transmembrane
• Transmembrane helix
• Transport
• Voltage-gated channel

InteractionsUniProt · HPA

Protein binding partners of NALCN in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CHRM3
• UNC80