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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
Type of variant: help LP/P [Disclaimer]
Residue change: help From Tyrosine (Y) to Serine (S) at position 578 (Y578S, p.Tyr578Ser).
Physico-chemical properties: help Change from large size and aromatic (Y) to small size and polar (S)
BLOSUM score: help -2
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.
Other resources: help


Sequence information Variant position: help 578
Protein sequence length: help 1738
Location on the sequence: help DVMDQTLNAVGHMWAPVVAI Y FILYHLFATLILLSLFVAVI
Residue conservation: help
Human                         DVMDQTLNAVGHMWAPVVAIYFILYHLFATLILLSLFVAVI

Mouse                         DVMDQTLNAVGHMWAPLVAIYFILYHLFATLILLSLFVAVI

Rat                           DVMDQTLNAVGHMWAPLVAIYFILYHLFATLILLSLFVAVI

Sequence annotation in neighborhood: help
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.