UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1174

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 Isoleucine (I) to Asparagine (N) at position 1174 (I1174N, p.Ile1174Asn).

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 medium size and hydrophobic (I) to medium size and polar (N)

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:

Growth retardation, impaired intellectual development, hypotonia, and hepatopathy (GRIDHH) [MIM:617093]: An autosomal recessive disorder characterized by severe growth retardation with prenatal onset, intellectual disability, muscular hypotonia, and hepatic dysfunction. {ECO:0000269|PubMed:27426735}. 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 GRIDHH.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs886037873 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1174

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

Protein sequence length:

1262

The length of the canonical sequence.

Location on the sequence:

VTAGSAPSLINSSSTLLCQY I NLQLLNAKPQECLMGTVGTL

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                         VTAGSAPSLINSSSTLLCQYINLQLLNAKPQECLMGTVGTL

Mouse                         VTAGASPSPISSPSTLLCQYLNLQLLNAEPQECLTGTVGTL

Caenorhabditis elegans        -----------------------DLWN-----------GKI

Slime mold                    -----------------------------------------

Baker's yeast                 -----------------------------------------

Fission yeast                 -----------------------------------------

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 – 1262	Isoleucine--tRNA ligase, cytoplasmic

Literature citations

Biallelic IARS mutations cause growth retardation with prenatal onset, intellectual disability, muscular hypotonia, and infantile hepatopathy.
Kopajtich R.; Murayama K.; Janecke A.R.; Haack T.B.; Breuer M.; Knisely A.S.; Harting I.; Ohashi T.; Okazaki Y.; Watanabe D.; Tokuzawa Y.; Kotzaeridou U.; Koelker S.; Sauer S.; Carl M.; Straub S.; Entenmann A.; Gizewski E.; Feichtinger R.G.; Mayr J.A.; Lackner K.; Strom T.M.; Meitinger T.; Mueller T.; Ohtake A.; Hoffmann G.F.; Prokisch H.; Staufner C.;
Am. J. Hum. Genet. 99:414-422(2016)
Cited for: INVOLVEMENT IN GRIDHH; VARIANTS GRIDHH GLY-370; LEU-437; ASP-992 AND ASN-1174; SUBCELLULAR LOCATION; TISSUE SPECIFICITY;

UniProtKB/Swiss-Prot P41252: Variant p.Ile1174Asn