UniProtKB/Swiss-Prot Q9UHD2: Variant p.Gly159Ala

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

159 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 Glycine (G) to Alanine (A) at position 159 (G159A, p.Gly159Ala). 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 small size and hydrophobic (A) 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 IIAE8; loss of kinase activity; loss of autophosphorylation at S-172; loss of IFNB induction. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1555202947 [ dbSNP | Ensembl ]

Sequence information Variant position:

159 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:

GNIMRVIGEDGQSVYKLTDF G AARELEDDEQFVSLYGTEEY 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                         GNIMRVIGEDGQSVYKLTDFGAARELEDDEQFVSLYGTEEY

Mouse                         GNIMRVIGEDGQSVYKLTDFGAARELEDDEQFVSLYGTEEY

Xenopus laevis                GNIMREIGEDGKSVYKLTDFGAARELEDDEQFVSLYGTEEY

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
Domain	9 – 310	Protein kinase
Modified residue	172 – 172	Phosphoserine; by autocatalysis and IKKB
Mutagenesis	172 – 172	S -> A. Loss of kinase activity. No effect on dimerization. Loss of USP38-mediated degradation.
Mutagenesis	172 – 172	S -> E. Decreased kinase activity.

Literature citations
Heterozygous TBK1 mutations impair TLR3 immunity and underlie herpes simplex encephalitis of childhood.
Herman M.; Ciancanelli M.; Ou Y.H.; Lorenzo L.; Klaudel-Dreszler M.; Pauwels E.; Sancho-Shimizu V.; Perez de Diego R.; Abhyankar A.; Israelsson E.; Guo Y.; Cardon A.; Rozenberg F.; Lebon P.; Tardieu M.; Heropolitanska-Pliszka E.; Chaussabel D.; White M.A.; Abel L.; Zhang S.Y.; Casanova J.L.;
J. Exp. Med. 209:1567-1582(2012)
Cited for: INVOLVEMENT IN IIAE8; VARIANTS IIAE8 ALA-50 AND ALA-159; CHARACTERIZATION OF VARIANTS IIAE8 ALA-50 AND ALA-159; MUTAGENESIS OF LYS-38; PHOSPHORYLATION AT SER-172; FUNCTION; Inborn errors of type I IFN immunity in patients with life-threatening COVID-19.
Zhang Q.; Bastard P.; Liu Z.; Le Pen J.; Moncada-Velez M.; Chen J.; Ogishi M.; Sabli I.K.D.; Hodeib S.; Korol C.; Rosain J.; Bilguvar K.; Ye J.; Bolze A.; Bigio B.; Yang R.; Arias A.A.; Zhou Q.; Zhang Y.; Onodi F.; Korniotis S.; Karpf L.; Philippot Q.; Chbihi M.; Bonnet-Madin L.; Dorgham K.; Smith N.; Schneider W.M.; Razooky B.S.; Hoffmann H.H.; Michailidis E.; Moens L.; Han J.E.; Lorenzo L.; Bizien L.; Meade P.; Neehus A.L.; Ugurbil A.C.; Corneau A.; Kerner G.; Zhang P.; Rapaport F.; Seeleuthner Y.; Manry J.; Masson C.; Schmitt Y.; Schlueter A.; Le Voyer T.; Khan T.; Li J.; Fellay J.; Roussel L.; Shahrooei M.; Alosaimi M.F.; Mansouri D.; Al-Saud H.; Al-Mulla F.; Almourfi F.; Al-Muhsen S.Z.; Alsohime F.; Al Turki S.; Hasanato R.; van de Beek D.; Biondi A.; Bettini L.R.; D'Angio' M.; Bonfanti P.; Imberti L.; Sottini A.; Paghera S.; Quiros-Roldan E.; Rossi C.; Oler A.J.; Tompkins M.F.; Alba C.; Vandernoot I.; Goffard J.C.; Smits G.; Migeotte I.; Haerynck F.; Soler-Palacin P.; Martin-Nalda A.; Colobran R.; Morange P.E.; Keles S.; Coelkesen F.; Ozcelik T.; Yasar K.K.; Senoglu S.; Karabela S.N.; Rodriguez-Gallego C.; Novelli G.; Hraiech S.; Tandjaoui-Lambiotte Y.; Duval X.; Laouenan C.; Snow A.L.; Dalgard C.L.; Milner J.D.; Vinh D.C.; Mogensen T.H.; Marr N.; Spaan A.N.; Boisson B.; Boisson-Dupuis S.; Bustamante J.; Puel A.; Ciancanelli M.J.; Meyts I.; Maniatis T.; Soumelis V.; Amara A.; Nussenzweig M.; Garcia-Sastre A.; Krammer F.; Pujol A.; Duffy D.; Lifton R.P.; Zhang S.Y.; Gorochov G.; Beziat V.; Jouanguy E.; Sancho-Shimizu V.; Rice C.M.; Abel L.; Notarangelo L.D.; Cobat A.; Su H.C.; Casanova J.L.;
Science 370:0-0(2020)
Cited for: VARIANTS SER-24; LEU-152; ALA-159; 308-ARG--LEU-729 DEL; GLN-384; SER-388; THR-397; ILE-508; MET-522; THR-533; GLN-653 AND SER-659; CHARACTERIZATION OF VARIANTS SER-24; LEU-152; ALA-159; 308-ARG--LEU-729 DEL; GLN-384; SER-388; THR-397; ILE-508; MET-522; THR-533; GLN-653 AND SER-659; FUNCTION;

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.