UniProtKB/SwissProt variant VAR

Variant information

Variant position:

299

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 Tryptophan (W) at position 299 (R299W, p.Arg299Trp).

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 large size and aromatic (W)

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

Variant description:

In COQ10D4; decreased stability.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs201908721 [ dbSNP | Ensembl ]

Sequence information

Variant position:

299

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

Protein sequence length:

647

The length of the canonical sequence.

Location on the sequence:

QMLSIQDDAFINPHLAKIFE R VRQSADFMPLKQMMKTLNND

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                         QMLSIQDDAFINPHLAKIFERVRQSADFMPLKQMMKTLNND

Mouse                         QMLSIQDDAFINPHLAKIFERVRQSADFMPLKQMTKTLNSD

Rat                           QMLSIQDDAFINPHLAKIFERVRQSADFMPLKQMTKTLNND

Bovine                        QMLSIQDDAFINPHLAKIFDRVRQSADFMPLKQMMKTLNND

Zebrafish                     QMLSIQDDAFINPQLAKIFERVRQSADFMPIKQMTKALSND

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	163 – 647	Atypical kinase COQ8A, mitochondrial
Alternative sequence	1 – 484	Missing. In isoform 2.
Mutagenesis	279 – 279	Q -> RH. Does not affect selectivity for binding ADP or ATP.
Helix	291 – 302

Literature citations

Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable coenzyme Q biosynthesis.
Stefely J.A.; Reidenbach A.G.; Ulbrich A.; Oruganty K.; Floyd B.J.; Jochem A.; Saunders J.M.; Johnson I.E.; Minogue C.E.; Wrobel R.L.; Barber G.E.; Lee D.; Li S.; Kannan N.; Coon J.J.; Bingman C.A.; Pagliarini D.J.;
Mol. Cell 57:83-94(2015)
Cited for: PROTEIN SEQUENCE OF N-TERMINUS; X-RAY CRYSTALLOGRAPHY (1.64 ANGSTROMS) OF 256-647; FUNCTION; SUBCELLULAR LOCATION; PATHWAY; DOMAIN; ACTIVITY REGULATION; MUTAGENESIS OF LYS-276; GLN-279; ALA-339; LYS-358; GLU-405; GLU-411; ASP-488; ASN-493; ASP-507 AND ARG-611; CHARACTERIZATION OF VARIANTS COQ10D4 TRP-299; CYS-429; SER-549 AND LYS-551;

Adult-onset cerebellar ataxia due to mutations in CABC1/ADCK3.
Horvath R.; Czermin B.; Gulati S.; Demuth S.; Houge G.; Pyle A.; Dineiger C.; Blakely E.L.; Hassani A.; Foley C.; Brodhun M.; Storm K.; Kirschner J.; Gorman G.S.; Lochmuller H.; Holinski-Feder E.; Taylor R.W.; Chinnery P.F.;
J. Neurol. Neurosurg. Psych. 83:174-178(2012)
Cited for: VARIANTS COQ10D4 TRP-213; CYS-271; ASP-272; VAL-272; TRP-299; THR-304; VAL-304; CYS-429; SER-549 AND LYS-551;

ADCK3 mutations with epilepsy, stroke-like episodes and ataxia: a POLG mimic?
Hikmat O.; Tzoulis C.; Knappskog P.M.; Johansson S.; Boman H.; Sztromwasser P.; Lien E.; Brodtkorb E.; Ghezzi D.; Bindoff L.A.;
Eur. J. Neurol. 23:1188-1194(2016)
Cited for: VARIANTS COQ10D4 TRP-299 AND VAL-578;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q8NI60: Variant p.Arg299Trp