UniProtKB/Swiss-Prot Q8IZF0: Variant p.Arg1181Gln

Sodium leak channel NALCN
Gene: NALCN
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Variant information Variant position:

1181 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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:

From Arginine (R) to Glutamine (Q) at position 1181 (R1181Q, p.Arg1181Gln). 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:

Change from large size and basic (R) to medium size and polar (Q) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

1 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:

In CLIFAHDD; uncertain significance; also found in patients with neurodevelopmental disease and hypotonia; uncertain significance. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs786201003 [ dbSNP | Ensembl ]

Sequence information Variant position:

1181 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1738 The length of the canonical sequence.
Location on the sequence:

ENKGTALLTVDQRRWEDLKS R LKIAQPLHLPPRPDNDGFRA 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:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         ENKGTALLTVDQRRWEDLKSRLKIAQPLHLPPRPDNDGFRA

Mouse                         ENKGTALLTVDQRRWEDLKSRLKIAQPLHLPPRPDNDGFRA

Rat                           ENKGTALLTVDQRRWEDLKSRLKIAQPLHLPPRPDNDGFRA

Sequence annotation in neighborhood:

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.

Type	Positions	Description
Chain	1 – 1738	Sodium leak channel NALCN
Topological domain	1160 – 1210	Cytoplasmic
Alternative sequence	219 – 1738	Missing. In isoform 3.
Alternative sequence	669 – 1738	Missing. In isoform 2.
Helix	1170 – 1184

Literature citations
Structure of the human sodium leak channel NALCN.
Kschonsak M.; Chua H.C.; Noland C.L.; Weidling C.; Clairfeuille T.; Bahlke O.O.; Ameen A.O.; Li Z.R.; Arthur C.P.; Ciferri C.; Pless S.A.; Payandeh J.;
Nature 587:313-318(2020)
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS) IN COMPLEX WITH NALF1; FUNCTION; CHARACTERIZATION OF VARIANTS CLIFAHDD PHE-590; GLN-1181 AND MET-1446; CHARACTERIZATION OF VARIANT IHPRF1 LEU-1287; DISULFIDE BOND; GLYCOSYLATION AT ASN-1064; SUBCELLULAR LOCATION; TOPOLOGY; A gain-of-function mutation in NALCN in a child with intellectual disability, ataxia, and arthrogryposis.
Aoyagi K.; Rossignol E.; Hamdan F.F.; Mulcahy B.; Xie L.; Nagamatsu S.; Rouleau G.A.; Zhen M.; Michaud J.L.;
Hum. Mutat. 36:753-757(2015)
Cited for: VARIANT CLIFAHDD GLN-1181; De novo missense mutations in NALCN cause developmental and intellectual impairment with hypotonia.
Fukai R.; Saitsu H.; Okamoto N.; Sakai Y.; Fattal-Valevski A.; Masaaki S.; Kitai Y.; Torio M.; Kojima-Ishii K.; Ihara K.; Chernuha V.; Nakashima M.; Miyatake S.; Tanaka F.; Miyake N.; Matsumoto N.;
J. Hum. Genet. 61:451-455(2016)
Cited for: VARIANTS VAL-312; PHE-1020 AND GLN-1181;

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.