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UniProtKB/Swiss-Prot Q9UHD2: Variant p.Arg47His

Serine/threonine-protein kinase TBK1
Gene: TBK1
Variant information

Variant position:  47
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  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:  From Arginine (R) to Histidine (H) at position 47 (R47H, p.Arg47His).
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 large size and basic (R) to medium size and polar (H)
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

Variant description:  In FTDALS4; loss of kinase activity.
Any additional useful information about the variant.



Sequence information

Variant position:  47
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:   RHKKTGDLFAIKVFNNISFL  R PVDVQMREFEVLKKLNHKNI
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                         RHKKTGDLFAIKVFNNISFLRPVDVQMREFEVLKKLNHKNI

Mouse                         RHKKTGDLYAVKVFNNISFLRPVDVQMREFEVLKKLNHKNI

Xenopus laevis                RNKKTGDLYAVKVFNSLSFQRPADVQMREFEVLKKLNHKNI

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 – 729 Serine/threonine-protein kinase TBK1
Domain 9 – 310 Protein kinase
Binding site 38 – 38 ATP
Cross 30 – 30 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Mutagenesis 30 – 30 K -> R. Decreases ubiquitination. Abolishes ubiquitination, phosphorylation and kinase activity; when associated with R-401.
Mutagenesis 33 – 33 D -> A. Decreases phosphorylation and kinase activity.
Mutagenesis 38 – 38 K -> A. Loss of kinase activity.


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;

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.