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UniProtKB/Swiss-Prot P15104: Variant p.Arg341Cys

Glutamine synthetase
Gene: GLUL
Variant information

Variant position:  341
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 Arginine (R) to Cysteine (C) at position 341 (R341C, p.Arg341Cys).
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 (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Congenital systemic glutamine deficiency (CSGD) [MIM:610015]: Rare developmental disorder with severe brain malformation resulting in multi-organ failure and neonatal death. Glutamine is largely absent from affected patients serum, urine and cerebrospinal fluid. {ECO:0000269|PubMed:16267323}. 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 CSGD; suggests reduced glutamine synthetase activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  341
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  373
The length of the canonical sequence.

Location on the sequence:   ASIRIPRTVGQEKKGYFEDR  R PSANCDPFSVTEALIRTCLL
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                         ASIRIPRTVGQEKKGYFEDRRPSANCDPFSVTEALIRT-CLL

                              ASIRIPRTVGQEKKGYFEDRRPSANCDPFSVTEALIRT-CL

Mouse                         ASIRIPRTVGQEKKGYFEDRRPSANCDPYAVTEAIVRT-CL

Rat                           ASIRIPRIVGQEKKGYFEDRRPSANCDPYAVTEAIVRT-CL

Pig                           ASIRIPRTGGQEKKGYFEDRRPSANCDPFAVTEALIRT-CL

Bovine                        ASIRIPRTVGQEKKGYFEDRRPSANCDPFAVTEALIRT-CL

Chicken                       ASIRIPRNVGHEKKGYFEDRGPSANCDPYAVTEALVRT-CL

Xenopus laevis                ASIRIPRQVGQEGYGYFEDRRPAANCDPYAVTEALVRT-TI

Caenorhabditis elegans        CSIRIPRQVAAERKGYLEDRRPSSNCDPYQVTAMIAQS---

Baker's yeast                 SSIRIPRSVAKEGYGYFEDRRPASNIDPYLVTGIMCETVCG

Fission yeast                 ASVRIPRSVAMNGCGYFEDRRPASSIDPYLVTGIITET---

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 2 – 373 Glutamine synthetase
Metal binding 338 – 338 Manganese 1
Binding site 324 – 324 ATP
Binding site 340 – 340 L-glutamate
Modified residue 343 – 343 Phosphoserine
Mutagenesis 324 – 324 R -> AC. Decreases ribolosomal 40S subunit synthesis. Loss of nucleolar location of BYSL.


Literature citations

Congenital glutamine deficiency with glutamine synthetase mutations.
Haeberle J.; Goerg B.; Rutsch F.; Schmidt E.; Toutain A.; Benoist J.-F.; Gelot A.; Suc A.-L.; Hoehne W.; Schliess F.; Haeussinger D.; Koch H.G.;
N. Engl. J. Med. 353:1926-1933(2005)
Cited for: VARIANTS CSGD CYS-324 AND CYS-341; CHARACTERIZATION OF VARIANTS CSGD CYS-324 AND CYS-341; FUNCTION; CATALYTIC ACTIVITY;

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.