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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13148: Variant p.Ala315Thr

TAR DNA-binding protein 43
Gene: TARDBP
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Variant information Variant position: help 315 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Alanine (A) to Threonine (T) at position 315 (A315T, p.Ala315Thr). 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: help Change from small size and hydrophobic (A) to medium size and polar (T) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 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
Variant description: help In ALS10; triggers mitochondrial DNA release into the cytosol, which is then detected by CGAS, leading to activation of the cGAS-STING pathway and autoinflammation; slight reduction in interaction with PPIA/CYPA. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 315 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 414 The length of the canonical sequence.
Location on the sequence: help GGAGLGNNQGSNMGGGMNFG A FSINPAMMAAAQAALQSSWG 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         GGAGLGNNQGSNM--GGGMNFGAFSINPAMMAAAQAALQSSWG

Mouse                         GGAGLGNNQGGNM--GGGMNFGAFSINPAMMAAAQAALQSS

Chicken                       GGGGLGNNQGSNM--GGGMNFGAFSINPAMMAAAQAALQSS

Xenopus tropicalis            SSGALGNNQGGNMGGGGGMNFGAFSINPAMMAAAQAALQSS

Caenorhabditis elegans        -----------------------------------------
Sequence annotation in neighborhood: help 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
Region 216 – 414 Interaction with UBQLN2
Beta strand 306 – 316



Literature citations
TDP-43 A315T mutation in familial motor neuron disease.
Gitcho M.A.; Baloh R.H.; Chakraverty S.; Mayo K.; Norton J.B.; Levitch D.; Hatanpaa K.J.; White C.L. III; Bigio E.H.; Caselli R.; Baker M.; Al-Lozi M.T.; Morris J.C.; Pestronk A.; Rademakers R.; Goate A.M.; Cairns N.J.;
Ann. Neurol. 63:535-538(2008)
Cited for: VARIANT ALS10 THR-315; TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis.
Kabashi E.; Valdmanis P.N.; Dion P.; Spiegelman D.; McConkey B.J.; Vande Velde C.; Bouchard J.-P.; Lacomblez L.; Pochigaeva K.; Salachas F.; Pradat P.-F.; Camu W.; Meininger V.; Dupre N.; Rouleau G.A.;
Nat. Genet. 40:572-574(2008)
Cited for: VARIANTS ALS10 GLY-169; SER-287; THR-315; CYS-348; SER-361; THR-382; ASP-390 AND SER-390; VARIANT VAL-90; Peptidylprolyl isomerase A governs TARDBP function and assembly in heterogeneous nuclear ribonucleoprotein complexes.
Lauranzano E.; Pozzi S.; Pasetto L.; Stucchi R.; Massignan T.; Paolella K.; Mombrini M.; Nardo G.; Lunetta C.; Corbo M.; Mora G.; Bendotti C.; Bonetto V.;
Brain 138:974-991(2015)
Cited for: CHARACTERIZATION OF VARIANTS ALS10 VAL-348; THR-315 AND SER-361; FUNCTION; SUBCELLULAR LOCATION; INTERACTION WITH PPIA; MUTAGENESIS OF 103-THR--SER-183; TDP-43 triggers mitochondrial DNA release via mPTP to activate cGAS/STING in ALS.
Yu C.H.; Davidson S.; Harapas C.R.; Hilton J.B.; Mlodzianoski M.J.; Laohamonthonkul P.; Louis C.; Low R.R.J.; Moecking J.; De Nardo D.; Balka K.R.; Calleja D.J.; Moghaddas F.; Ni E.; McLean C.A.; Samson A.L.; Tyebji S.; Tonkin C.J.; Bye C.R.; Turner B.J.; Pepin G.; Gantier M.P.; Rogers K.L.; McArthur K.; Crouch P.J.; Masters S.L.;
Cell 183:636-649(2020)
Cited for: CHARACTERIZATION OF VARIANTS ALS10 THR-315 AND LYS-331; SUBCELLULAR LOCATION;
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.