UniProtKB/SwissProt variant VAR

Variant information

Variant position:

571

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 Alanine (A) to Valine (V) at position 571 (A571V, p.Ala571Val).

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 small size and hydrophobic (A) to medium size and hydrophobic (V)

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

BLOSUM score:

0

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:

Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 (FTDALS4) [MIM:616439]: A neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. {ECO:0000269|PubMed:25803835, ECO:0000269|PubMed:25943890}. 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 FTDALS4.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs765035140 [ dbSNP | Ensembl ]

Sequence information

Variant position:

571

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

Protein sequence length:

729

The length of the canonical sequence.

Location on the sequence:

KLQVLLNCMTEIYYQFKKDK A ERRLAYNEEQIHKFDKQKLY

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                         KLQVLLNCMTEIYYQFKKDKAERRLAYNEEQIHKFDKQKLY

Mouse                         KLQVLLNCITEIYYQFKKDKAERRLAYNEEQIHKFDKQKLY

Xenopus laevis                KLQVLLSLITEIYCQFKKDKAQRRLSYNEEQIHKFDKQKLC

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 – 729	Serine/threonine-protein kinase TBK1
Coiled coil	407 – 657
Mutagenesis	577 – 577	Y -> A. Decreases kinase activity.
Mutagenesis	580 – 580	E -> A. Decreases kinase activity.
Mutagenesis	582 – 582	I -> A. Decreases kinase activity.
Mutagenesis	589 – 589	K -> D. Decreases phosphorylation and kinase activity.
Helix	548 – 571

Literature citations

Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia.
Freischmidt A.; Wieland T.; Richter B.; Ruf W.; Schaeffer V.; Mueller K.; Marroquin N.; Nordin F.; Huebers A.; Weydt P.; Pinto S.; Press R.; Millecamps S.; Molko N.; Bernard E.; Desnuelle C.; Soriani M.H.; Dorst J.; Graf E.; Nordstroem U.; Feiler M.S.; Putz S.; Boeckers T.M.; Meyer T.; Winkler A.S.; Winkelman J.; de Carvalho M.; Thal D.R.; Otto M.; Braennstroem T.; Volk A.E.; Kursula P.; Danzer K.M.; Lichtner P.; Dikic I.; Meitinger T.; Ludolph A.C.; Strom T.M.; Andersen P.M.; Weishaupt J.H.;
Nat. Neurosci. 18:631-636(2015)
Cited for: INVOLVEMENT IN FTDALS4; VARIANTS FTDALS4 HIS-47; CYS-105; THR-305; GLN-308; GLN-357; ARG-559; VAL-571; VAL-598; GLU-643 DEL AND LYS-696; CHARACTERIZATION OF VARIANTS FTDALS4 HIS-47; GLN-308; GLN-357; ARG-559 AND LYS-696;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9UHD2: Variant p.Ala571Val