UniProtKB/Swiss-Prot Q9BTU6: Variant p.Arg275Trp

Phosphatidylinositol 4-kinase type 2-alpha
Gene: PI4K2A
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Variant information Variant position:

275 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 275 (R275W, p.Arg275Trp). 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:

Found in a patient with cutis laxa, a choreoathetoid movement disorder, dysmorphic features and intellectual disability; uncertain significance; reduced phosphatidylinositol 4-kinase activity in patient cells; similar to the wild type, it rescues low PI4P levels when transfected in PI4K2A-null cells suggesting no effect on function in PI4P synthesis; does not affect localization to intracellular membranes. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs200233778 [ dbSNP | Ensembl ]

Sequence information Variant position:

275 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

479 The length of the canonical sequence.
Location on the sequence:

PKVGSFQLFVEGYKDADYWL R RFEAEPLPENTNRQLLLQFE 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                         PKVGSFQLFVEGYKDADYWLRRFEAEPLPENTNRQLLLQFE

Mouse                         PKVGSFQLFVEGYKDADYWLRRFEAEPLPENTNRQLLLQFE

Rat                           PKVGSFQLFVEGYKDADYWLRRFEAEPLPENTNRQLLLQFE

Xenopus laevis                PKVGSFQIFVKSYKDADYWLRRFEADPLPENTNRQLQLQFE

Xenopus tropicalis            PKVGSFQLFVKGYKDADYWLRRFEADPLPENTNRQLQLQFE

Zebrafish                     PKVGSFQIFVEGYKDADFWLRRFEAEPLPENTNRQLQLQFE

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 – 479	Phosphatidylinositol 4-kinase type 2-alpha
Domain	124 – 453	PI3K/PI4K catalytic
Region	268 – 276	Important for interaction with membranes
Mutagenesis	263 – 263	F -> A. Abolishes enzyme activity; when associated with A-345.
Mutagenesis	269 – 269	D -> A. Reduces enzyme activity by half.
Mutagenesis	275 – 275	R -> A. Reduces enzyme activity.
Mutagenesis	275 – 275	R -> E. Reduces enzyme activity, probably due to impaired membrane-association; when associated with E-129 and E-276.
Mutagenesis	276 – 276	R -> E. Reduces enzyme activity, probably due to impaired membrane-association; when associated with E-129 and E-275.
Helix	270 – 279

Literature citations
Novel defect in phosphatidylinositol 4-kinase type 2-alpha (PI4K2A) at the membrane-enzyme interface is associated with metabolic cutis laxa.
Mohamed M.; Gardeitchik T.; Balasubramaniam S.; Guerrero-Castillo S.; Dalloyaux D.; van Kraaij S.; Venselaar H.; Hoischen A.; Urban Z.; Brandt U.; Al-Shawi R.; Simons J.P.; Frison M.; Ngu L.H.; Callewaert B.; Spelbrink H.; Kallemeijn W.W.; Aerts J.M.F.G.; Waugh M.G.; Morava E.; Wevers R.A.;
J. Inherit. Metab. Dis. 43:1382-1391(2020)
Cited for: VARIANT TRP-275; CHARACTERIZATION OF VARIANT TRP-275; PI4K2A deficiency causes innate error in intracellular trafficking with developmental and epileptic-dyskinetic encephalopathy.
Dafsari H.S.; Pemberton J.G.; Ferrer E.A.; Yammine T.; Farra C.; Mohammadi M.H.; Ghayoor Karimiani E.; Hashemi N.; Souaid M.; Sabbagh S.; Najarzadeh Torbati P.; Khan S.; Roze E.; Moreno-De-Luca A.; Bertoli-Avella A.M.; Houlden H.; Balla T.; Maroofian R.;
Ann. Clin. Transl. Neurol. 9:1345-1358(2022)
Cited for: VARIANT NEDMSB 309-ARG--TRP-479 DEL; INVOLVEMENT IN NEDMSB; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT NEDMSB 309-ARG--TRP-479 DEL; CHARACTERIZATION OF VARIANT TRP-275;

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.