UniProtKB/SwissProt variant VAR

Glutamine synthetase
Gene: GLUL
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Variant information Variant position:

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

LP/P [Disclaimer] 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 Cysteine (C) at position 324 (R324C, p.Arg324Cys). 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
Variant description:

In GLND; reduced glutamine synthetase activity; decreased function in ribosomal 40S subunit synthesis associated with loss of nucleolar location of BYSL. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs80358214 [ dbSNP | Ensembl ]

Sequence information Variant position:

324 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:

HETSNINDFSAGVANRSASI R IPRTVGQEKKGYFEDRRPSA 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                         HETSNINDFSAGVANRSASIRIPRTVGQEKKGYFEDRRPSA

                              HETSNINDFSAGVANRGASIRIPRTVGQEKKGYFEDRRPSA

Mouse                         HETSNINDFSAGVANRGASIRIPRTVGQEKKGYFEDRRPSA

Rat                           HETSNINDFSAGVANRSASIRIPRIVGQEKKGYFEDRRPSA

Pig                           HETSNINDFSAGVANRGASIRIPRTGGQEKKGYFEDRRPSA

Bovine                        HETSNINDFSAGVANRGASIRIPRTVGQEKKGYFEDRRPSA

Chicken                       HETSSIHEFSAGVANRGASIRIPRNVGHEKKGYFEDRGPSA

Xenopus laevis                HETSSIHEFSAGVANRGASIRIPRQVGQEGYGYFEDRRPAA

Caenorhabditis elegans        HETSSADKFSWGVANRGCSIRIPRQVAAERKGYLEDRRPSS

Baker's yeast                 HETASMTAFSSGVANRGSSIRIPRSVAKEGYGYFEDRRPAS

Fission yeast                 HETGSIDKFTYGVADRGASVRIPRSVAMNGCGYFEDRRPAS

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	2 – 373	Glutamine synthetase
Domain	113 – 373	GS catalytic
Binding site	319 – 319
Binding site	319 – 319
Binding site	324 – 324
Binding site	338 – 338
Binding site	340 – 340
Modified residue	343 – 343	Phosphoserine
Mutagenesis	324 – 324	R -> A. Decreases ribosomal 40S subunit synthesis. Loss of nucleolar location of BYSL.
Beta strand	321 – 325

Literature citations
Genome-wide RNAi Screening Identifies Protein Modules Required for 40S Subunit Synthesis in Human Cells.
Badertscher L.; Wild T.; Montellese C.; Alexander L.T.; Bammert L.; Sarazova M.; Stebler M.; Csucs G.; Mayer T.U.; Zamboni N.; Zemp I.; Horvath P.; Kutay U.;
Cell Rep. 13:2879-2891(2015)
Cited for: FUNCTION; MUTAGENESIS OF ARG-324; CHARACTERIZATION OF VARIANT GLND CYS-324; 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 GLND CYS-324 AND CYS-341; CHARACTERIZATION OF VARIANTS GLND CYS-324 AND CYS-341; FUNCTION; CATALYTIC ACTIVITY; INVOLVEMENT IN GLND; Clustered de novo start-loss variants in GLUL result in a developmental and epileptic encephalopathy via stabilization of glutamine synthetase.
Jones A.G.; Aquilino M.; Tinker R.J.; Duncan L.; Jenkins Z.; Carvill G.L.; DeWard S.J.; Grange D.K.; Hajianpour M.J.; Halliday B.J.; Holder-Espinasse M.; Horvath J.; Maitz S.; Nigro V.; Morleo M.; Paul V.; Spencer C.; Esterhuizen A.I.; Polster T.; Spano A.; Gomez-Lozano I.; Kumar A.; Poke G.; Phillips J.A. III; Underhill H.R.; Gimenez G.; Namba T.; Robertson S.P.;
Am. J. Hum. Genet. 111:729-741(2024)
Cited for: CHARACTERIZATION OF VARIANTS GLND CYS-324 AND CYS-341; MUTAGENESIS OF 1-MET--TYR-17; INDUCTION; INVOLVEMENT IN DEE116;

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.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P15104: Variant p.Arg324Cys