UniProtKB/Swiss-Prot P23921: Variant p.Asn427Lys

Ribonucleoside-diphosphate reductase large subunit
Gene: RRM1
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Variant information Variant position:

427 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 Asparagine (N) to Lysine (K) at position 427 (N427K, p.Asn427Lys). 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 medium size and polar (N) to large size and basic (K) 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:

Found at heterozygosity in a patient with features of progressive external ophthalmoplegia with mitochondrial DNA deletions; uncertain significance. Any additional useful information about the variant.

Sequence information Variant position:

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

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

YKDSCNRKSNQQNLGTIKCS N LCTEIVEYTSKDEVAVCNLA 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                         YKDSCNRKSNQQNLGTIKCSNLCTEIVEYTSKDEVAVCNLA

Mouse                         YKDSCNRKSNQQNLGTIKCSNLCTEIVEYTSKDEVAVCNLA

Zebrafish                     YKDACNRKSNRQNLGTIKCSNLCTEIVEYTSADEVAVCNLA

Caenorhabditis elegans        YKDAANRKSNQQNLGTIKCSNLCTEIIEYSAPDEIAVCNLA

Drosophila                    FKDACNRKSNQQNVGTIKCSNLCTEIVEYSAPDEIAVCNLA

Slime mold                    YKDACNAKSNQKNLGTISSSNLCTEIIQYTSPDEIAVCNLA

Baker's yeast                 YKDACNRKSNQKNLGVIKSSNLCCEIVEYSAPDETAVCNLA

Fission yeast                 YKDSCNRKSNQKNVGTIRCSNLCTEIVEYSSPDEVAVCNLA

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 – 792	Ribonucleoside-diphosphate reductase large subunit
Active site	427 – 427	Proton acceptor
Active site	429 – 429	Cysteine radical intermediate
Active site	431 – 431	Proton acceptor
Binding site	427 – 427
Binding site	431 – 431
Site	444 – 444	Important for hydrogen atom transfer
Disulfide bond	218 – 444	Redox-active

Literature citations
RRM1 variants cause a mitochondrial DNA maintenance disorder via impaired de novo nucleotide synthesis.
Shintaku J.; Pernice W.M.; Eyaid W.; Gc J.B.; Brown Z.P.; Juanola-Falgarona M.; Torres-Torronteras J.; Sommerville E.W.; Hellebrekers D.M.; Blakely E.L.; Donaldson A.; van de Laar I.; Leu C.S.; Marti R.; Frank J.; Tanji K.; Koolen D.A.; Rodenburg R.J.; Chinnery P.F.; Smeets H.J.M.; Gorman G.S.; Bonnen P.E.; Taylor R.W.; Hirano M.;
J. Clin. Invest. 132:0-0(2022)
Cited for: VARIANTS PEOB6 HIS-381 AND CYS-381; VARIANT LYS-427; INVOLVEMENT IN PEOB6;

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.