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UniProtKB/Swiss-Prot Q8IZF0: Variant p.Trp1287Leu

Sodium leak channel non-selective protein
Gene: NALCN
Variant information

Variant position:  1287
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Tryptophan (W) to Leucine (L) at position 1287 (W1287L, p.Trp1287Leu).
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 aromatic (W) to medium size and hydrophobic (L)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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

Involvement in disease:  Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 (IHPRF1) [MIM:615419]: A neurodegenerative disease characterized by variable degrees of hypotonia, speech impairment, intellectual disability, pyramidal signs, subtle facial dysmorphism, and chronic constipation. Some patients manifest neuroaxonal dystrophy, optic atrophy, unmyelinated axons and spheroid bodies in tissue biopsies. {ECO:0000269|PubMed:23749988, ECO:0000269|PubMed:24075186}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In IHPRF1.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  1287
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:   GFWQSRRNRYDLLVTSLGVV  W VVLHFALLNAYTYMMGACVI
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                         GFWQSRRNRYDLLVTSLGVVWVVLHFALLNAYTYMMGACVI

Mouse                         GFWQSRRNRYDLLVTSLGVVWVVLHFALLNAYTYMMGACVI

Rat                           GFWQSRRNRYDLLVTSLGVVWVVLHFALLNAYTYMMGACVI

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.

TypePositionsDescription
Chain 1 – 1738 Sodium leak channel non-selective protein
Transmembrane 1278 – 1298 Helical; Name=S3 of repeat IV
Topological domain 1299 – 1299 Extracellular
Alternative sequence 219 – 1738 Missing. In isoform 3.
Alternative sequence 669 – 1738 Missing. In isoform 2.


Literature citations

Mutations in NALCN cause an autosomal-recessive syndrome with severe hypotonia, speech impairment, and cognitive delay.
Al-Sayed M.D.; Al-Zaidan H.; Albakheet A.; Hakami H.; Kenana R.; Al-Yafee Y.; Al-Dosary M.; Qari A.; Al-Sheddi T.; Al-Muheiza M.; Al-Qubbaj W.; Lakmache Y.; Al-Hindi H.; Ghaziuddin M.; Colak D.; Kaya N.;
Am. J. Hum. Genet. 93:721-726(2013)
Cited for: VARIANT IHPRF1 LEU-1287;

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.