UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1249

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

Type of variant:

Unclassified

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 Threonine (T) to Isoleucine (I) at position 1249 (T1249I, p.Thr1249Ile).

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

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-1

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:

Amyotrophic lateral sclerosis (ALS) [MIM:105400]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. {ECO:0000269|PubMed:15326253, ECO:0000269|PubMed:16240349}. Note=Disease susceptibility is associated with variations 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 ALS; unknown pathological significance.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs72466496 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1249

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

Protein sequence length:

1278

The length of the canonical sequence.

Location on the sequence:

SAFLRAKEEQQDDTVYMGKV T FSCAAGFGQRHRLVLTQEQL

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                         SAFLRAKEEQQDDTVYMGKVTFSCAAGFGQRHRLVLTQEQL

Mouse                         SAFLRAKEEQQDDTVYMGKVTFSCAAGLGQRHRLVLTQEQL

Rat                           SAFLRAKEEQQDDTVYMGKVTFSCAAGLGQRHRLVLTQEQL

Chicken                       S---------------------ACSPPRPS-----------

Xenopus laevis                TDFIKAKEEKKEDTVYIGKVTLSCQPGQGQIHKLVLTPEQL

Drosophila                    VDVKRVLQI--------------------------------

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 – 1278	Dynactin subunit 1
Region	911 – 1278	Interaction with HPS6

Literature citations

Point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS.
Muench C.; Sedlmeier R.; Meyer T.; Homberg V.; Sperfeld A.D.; Kurt A.; Prudlo J.; Peraus G.; Hanemann C.O.; Stumm G.; Ludolph A.C.;
Neurology 63:724-726(2004)
Cited for: INVOLVEMENT IN ALS; VARIANTS ALS THR-571; TRP-785 AND ILE-1249;

The p150 subunit of dynactin (DCTN1) gene in multiple sclerosis.
Muench C.; Meyer R.; Linke P.; Meyer T.; Ludolph A.C.; Haas J.; Hemmer B.;
Acta Neurol. Scand. 116:231-234(2007)
Cited for: VARIANTS VAL-196; GLN-495 AND ILE-1249;

Characterization of DCTN1 genetic variability in neurodegeneration.
Vilarino-Gueell C.; Wider C.; Soto-Ortolaza A.I.; Cobb S.A.; Kachergus J.M.; Keeling B.H.; Dachsel J.C.; Hulihan M.M.; Dickson D.W.; Wszolek Z.K.; Uitti R.J.; Graff-Radford N.R.; Boeve B.F.; Josephs K.A.; Miller B.; Boylan K.B.; Gwinn K.; Adler C.H.; Aasly J.O.; Hentati F.; Destee A.; Krygowska-Wajs A.; Chartier-Harlin M.-C.; Ross O.A.; Rademakers R.; Farrer M.J.;
Neurology 72:2024-2028(2009)
Cited for: VARIANT ILE-1249;

UniProtKB/Swiss-Prot Q14203: Variant p.Thr1249Ile