UniProtKB/SwissProt variant VAR

Variant information

Variant position:

344

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 Tyrosine (Y) to Cysteine (C) at position 344 (Y344C, p.Tyr344Cys).

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 (Y) to medium size and polar (C)

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:

Interstitial lung and liver disease (ILLD) [MIM:615486]: An autosomal recessive, life-threatening disorder characterized by respiratory insufficiency and progressive liver disease with onset in infancy or early childhood. Clinical features include failure to thrive, hypotonia, intermittent lactic acidosis, aminoaciduria, hypothyroidism, interstitial lung disease, pulmonary alveolar proteinosis, anemia, and liver canalicular cholestasis, steatosis, and iron deposition. {ECO:0000269|PubMed:24103465, ECO:0000269|PubMed:25913036}. 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 ILLD; when assayed in yeast, induces a slight growth retardation and reduction in methionine incorporation; may interfere with efficient substrate binding.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs766466297 [ dbSNP | Ensembl ]

Sequence information

Variant position:

344

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

Protein sequence length:

900

The length of the canonical sequence.

Location on the sequence:

EEGLTPQEICDKYHIIHADI Y RWFNISFDIFGRTTTPQQTK

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                         EEGLTPQEICDKYHIIHADIYRWFNISFDIFGRTTTPQQTK

Mouse                         EEGLTPREICDKYHAIHADIYRWFGISFDTFGRTTTPQQTK

Bovine                        EEGLTPQEICDKYHVIHADIYRWFNISFDFFGRTTTPQQTK

Xenopus laevis                EEGLTPQQICDKYNAIHTAIYQWFNISFDYFGRTTTQHQTT

Caenorhabditis elegans        QEGCTPRELCDKYHAIHKGIYEWFGIDFSHFGRTTTDHQTE

Slime mold                    SEGCTPKEICDKYHEIHKEIYEWFNISFDKFGRTSTNSQTE

Baker's yeast                 EEGVTPRQLCDKYHKIHSDVYKWFQIGFDYFGRTTTDKQTE

Fission yeast                 EEGVSPKELCDKYHALHKEVYDWFEIDFDHFGRTTTPKQTG

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 – 900	Methionine--tRNA ligase, cytoplasmic
Helix	329 – 346

Literature citations

Biallelic mutations of methionyl-tRNA synthetase cause a specific type of pulmonary alveolar proteinosis prevalent on Reunion island.
Hadchouel A.; Wieland T.; Griese M.; Baruffini E.; Lorenz-Depiereux B.; Enaud L.; Graf E.; Dubus J.C.; Halioui-Louhaichi S.; Coulomb A.; Delacourt C.; Eckstein G.; Zarbock R.; Schwarzmayr T.; Cartault F.; Meitinger T.; Lodi T.; de Blic J.; Strom T.M.;
Am. J. Hum. Genet. 96:826-831(2015)
Cited for: VARIANTS ILLD CYS-344; THR-393; LEU-567 AND VAL-605; VARIANTS LEU-206 AND GLN-727;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P56192: Variant p.Tyr344Cys