UniProtKB/Swiss-Prot O14936: Variant p.Arg28Leu

Peripheral plasma membrane protein CASK
Gene: CASK
Chromosomal location: Xp11.4
Variant information

Variant position:  28
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Arginine (R) to Leucine (L) at position 28 (R28L, p.Arg28Leu).
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 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:  FG syndrome 4 (FGS4) [MIM:300422]: FG syndrome (FGS) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. 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 FGS4; does not reveal significant alterations induced by the mutation substitution; causes a partial skipping of exon 2 of the protein.
Any additional useful information about the variant.



Sequence information

Variant position:  28
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  926
The length of the canonical sequence.

Location on the sequence:   FEDVYELCEVIGKGPFSVVR  R CINRETGQQFAVKIVDVAKF
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                         FEDVYELCEVIGKGPFSVVRRCINRETGQQFAVKIVDVAKF

Mouse                         FEDVYELCEVIGKGPFSVVRRCINRETGQQFAVKIVDVAKF

Rat                           FEDVYELCEVIGKGPFSVVRRCINRETGQQFAVKIVDVAKF

Drosophila                    FDDVYELCEVIGKGPFSIVRRCIHRESNQQFAVKIVDVAKF

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 – 926 Peripheral plasma membrane protein CASK
Domain 12 – 276 Protein kinase
Binding site 41 – 41 ATP
Alternative sequence 1 – 385 Missing. In isoform 5.
Beta strand 22 – 31


Literature citations

A missense mutation in CASK causes FG syndrome in an Italian family.
Piluso G.; D'Amico F.; Saccone V.; Bismuto E.; Rotundo I.L.; Di Domenico M.; Aurino S.; Schwartz C.E.; Neri G.; Nigro V.;
Am. J. Hum. Genet. 84:162-177(2009)
Cited for: VARIANT FGS4 LEU-28; CHARACTERIZATION OF VARIANT FGS4 LEU-28;

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.