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UniProtKB/Swiss-Prot O00764: Variant p.Arg220Gln

Pyridoxal kinase
Gene: PDXK
Variant information

Variant position:  220
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Arginine (R) to Glutamine (Q) at position 220 (R220Q, p.Arg220Gln).
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 (Q)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
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

Involvement in disease:  Neuropathy, hereditary motor and sensory, 6C, with optic atrophy (HMSN6C) [MIM:618511]: An autosomal recessive neurologic disorder characterized by childhood onset of axonal, sensorimotor polyneuropathy affecting mainly the lower limbs, and adult-onset optic atrophy. Clinical features include progressive distal muscle weakness and atrophy, significant standing and walking difficulties, areflexia, neurogenic pain and progressive visual impairment. {ECO:0000269|PubMed:31187503}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In HMSN6C; decreased pyridoxal kinase activity.
Any additional useful information about the variant.



Sequence information

Variant position:  220
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  312
The length of the canonical sequence.

Location on the sequence:   IVLGSQRRRNPAGSVVMERI  R MDIRKVDAVFVGTGDLFAAM
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                         IVLGSQRRRNPAGSVVMERIRMDI-RKVDAVFVGTGDLFAAM

Mouse                         IALGSQRMRKPDGSTVTQRIRMEM-RKVEAVFVGTGDLFAA

Rat                           MALGSQRMRKPDGSTVTQRIRMEM-RKVDPVFVGTGDLFAA

Pig                           IALGSQRTRSPDGSVATQRIRMEI-CKVDAVFVGTGDLFAA

Bovine                        MALGSQRTRAPDGSMVTQRIRMEM-HKVDAVFVGTGDLFAA

Sheep                         MALGSQRTRAPDGSVVTQRIRMEM-HKVDAVFVGTGDLFAA

Caenorhabditis elegans        RCYASVK-----GSHVY---RFTF-PRLVGQFVGTGDTFTS

Slime mold                    IVIGSTI-NDDDNNNKYNQFKIKVGPKFNDYYTGTGDLLSS

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 – 312 Pyridoxal kinase
Active site 235 – 235 Proton acceptor
Binding site 233 – 233 ATP
Modified residue 213 – 213 Phosphoserine
Mutagenesis 235 – 235 D -> A. 15-fold decrease in pyridoxal kinase activity, and a 7-fold decrease in affinity for pyridoxal.
Mutagenesis 235 – 235 D -> N. 2-fold decrease in pyridoxal kinase activity and pyridoxal affinity.
Beta strand 215 – 224


Literature citations

PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation.
Chelban V.; Wilson M.P.; Warman Chardon J.; Vandrovcova J.; Zanetti M.N.; Zamba-Papanicolaou E.; Efthymiou S.; Pope S.; Conte M.R.; Abis G.; Liu Y.T.; Tribollet E.; Haridy N.A.; Botia J.A.; Ryten M.; Nicolaou P.; Minaidou A.; Christodoulou K.; Kernohan K.D.; Eaton A.; Osmond M.; Ito Y.; Bourque P.; Jepson J.E.C.; Bello O.; Bremner F.; Cordivari C.; Reilly M.M.; Foiani M.; Heslegrave A.; Zetterberg H.; Heales S.J.R.; Wood N.W.; Rothman J.E.; Boycott K.M.; Mills P.B.; Clayton P.T.; Houlden H.;
Ann. Neurol. 86:225-240(2019)
Cited for: VARIANTS HMSN6C GLN-220 AND THR-228; CHARACTERIZATION OF VARIANTS HMSN6C GLN-220 AND THR-228; BIOPHYSICOCHEMICAL PROPERTIES; CATALYTIC ACTIVITY; FUNCTION; TISSUE SPECIFICITY; PATHWAY;

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.