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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q8IZF0: Variant p.Tyr578Ser

Sodium leak channel NALCN
Gene: NALCN
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Variant information Variant position: help 578 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Tyrosine (Y) to Serine (S) at position 578 (Y578S, p.Tyr578Ser). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Change from large size and aromatic (Y) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page
Variant description: help In CLIFAHDD and IHPRF1; nearly eliminates wild-type protein expression; dominant-negative mutation; decreases membrane expression; induces higher current density and slower inactivation. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 578 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1738 The length of the canonical sequence.
Location on the sequence: help DVMDQTLNAVGHMWAPVVAI Y FILYHLFATLILLSLFVAVI The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         DVMDQTLNAVGHMWAPVVAIYFILYHLFATLILLSLFVAVI

Mouse                         DVMDQTLNAVGHMWAPLVAIYFILYHLFATLILLSLFVAVI

Rat                           DVMDQTLNAVGHMWAPLVAIYFILYHLFATLILLSLFVAVI
Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 1 – 1738 Sodium leak channel NALCN
Transmembrane 570 – 599 Helical; Name=S6 of repeat II
Alternative sequence 219 – 1738 Missing. In isoform 3.
Mutagenesis 558 – 558 D -> A. Moderately more sensitive to Ca(2+) block.
Mutagenesis 561 – 561 D -> A. No effect on the blockage of NALCN pore by Ca(2+).
Helix 572 – 588



Literature citations
De novo mutations in NALCN cause a syndrome characterized by congenital contractures of the limbs and face, hypotonia, and developmental delay.
Chong J.X.; McMillin M.J.; Shively K.M.; Beck A.E.; Marvin C.T.; Armenteros J.R.; Buckingham K.J.; Nkinsi N.T.; Boyle E.A.; Berry M.N.; Bocian M.; Foulds N.; Uzielli M.L.; Haldeman-Englert C.; Hennekam R.C.; Kaplan P.; Kline A.D.; Mercer C.L.; Nowaczyk M.J.; Klein Wassink-Ruiter J.S.; McPherson E.W.; Moreno R.A.; Scheuerle A.E.; Shashi V.; Stevens C.A.; Carey J.C.; Monteil A.; Lory P.; Tabor H.K.; Smith J.D.; Shendure J.; Nickerson D.A.; Bamshad M.J.;
Am. J. Hum. Genet. 96:462-473(2015)
Cited for: INVOLVEMENT IN CLIFAHDD; VARIANTS CLIFAHDD PRO-177; ILE-312; GLY-313; SER-509; SER-578; PHE-590; PRO-1165 AND MET-1446; CHARACTERIZATION OF VARIANTS CLIFAHDD SER-509 AND SER-578; 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.; Impheng H.; Servant Z.; Lory P.; Monteil A.;
Sci. Rep. 9:11791-11791(2019)
Cited for: CHARACTERIZATION OF VARIANTS CLIFAHDD SER-509 AND SER-578; CHARACTERIZATION OF VARIANT IHPRF1 LEU-1287; SUBCELLULAR LOCATION; FUNCTION;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.