UniProtKB/Swiss-Prot Q13148: Variant p.Gly294Val

TAR DNA-binding protein 43
Gene: TARDBP
Chromosomal location: 1p36.23
Variant information

Variant position:  294
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Glycine (G) to Valine (V) at position 294 (G294V, p.Gly294Val).
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 glycine (G) to medium size and hydrophobic (V)
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:  Amyotrophic lateral sclerosis 10 (ALS10) [MIM:612069]: 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. 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 ALS10; a patient with bulbar signs and dementia.
Any additional useful information about the variant.



Sequence information

Variant position:  294
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  414
The length of the canonical sequence.

Location on the sequence:   GRFGGNPGGFGNQGGFGNSR  G GGAGLGNNQGSNMGGGMNFG
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                         GRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGG--MNFG

Mouse                         GRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGGNMGGG--MN

Chicken                       GRFGGNPGGFGNQGGFGNSRGGGGGLGNNQGSNMGGG--MN

Xenopus tropicalis            GRFPGPS--FGNQ-GYPNSRPSSGALGNNQGGNMGGGGGMN

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.

TypePositionsDescription
Chain 1 – 414 TAR DNA-binding protein 43
Compositional bias 274 – 413 Gly-rich
Modified residue 292 – 292 Phosphoserine


Literature citations

High frequency of TARDBP gene mutations in Italian patients with amyotrophic lateral sclerosis.
Corrado L.; Ratti A.; Gellera C.; Buratti E.; Castellotti B.; Carlomagno Y.; Ticozzi N.; Mazzini L.; Testa L.; Taroni F.; Baralle F.E.; Silani V.; D'Alfonso S.;
Hum. Mutat. 30:688-694(2009)
Cited for: VARIANTS ALS10 SER-267; SER-287; VAL-294; SER-295; ARG-295; ASN-332; ASP-335; VAL-337; PRO-379; CYS-379; THR-382 AND LEU-393;

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.