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UniProtKB/Swiss-Prot P03915: Variant p.Ala458Thr

NADH-ubiquinone oxidoreductase chain 5
Gene: MT-ND5
Variant information

Variant position:  458
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 Alanine (A) to Threonine (T) at position 458 (A458T, p.Ala458Thr).
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 small size and hydrophobic (A) to medium size and polar (T)
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 LHON; secondary mutation; does not seem to directly cause the disease.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  458
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  603
The length of the canonical sequence.

Location on the sequence:   PTLTNINENNPTLLNPIKRL  A AGSLFAGFLITNNISPASPF
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                         PTLTNINENNPTLLNPIKRLAAGSLFAGFLITNNISPASPF

Gorilla                       PTFANINENYSTLLNPIKRLTIGSLFAGFFITNNILPTSVP

                              SPMILINENNPLLINSIKRLLIGSVFAGYIISHSITPTTIP

Chimpanzee                    PTLTNINENNPTLLNPIKRLTIGSLFAGFLITNNILPMSTP

Mouse                         PPLISINENDPDLMNPIKRLAFGSIFAGFVISYNIPPTSIP

Rat                           SPLITINENNPNLINPIKRLALGSILAGFLISLNIPPTNIQ

Pig                           PPLVLINENNPLLINSIKRLLIGSIFAGFIISNNIPPMTVP

Bovine                        PTLVNINENNPLLINSIKRLLIGSLFAGYIISNNIPPTTIP

Rabbit                        PALIVINENNPLLINSIKRLALGSIFAGFLISNLITPNNVP

Sheep                         PTLININENNPFLINSIKRLLIGSLFAGFIISNNIPPMTIP

Cat                           NTLNLINENNTHLINSIKRLLIGSIFAGYLISYNIPPTTIP

Horse                         LPLTSINENNPFLINSIKRLLIGSIFAGFFISNNIYPTTVP

Chicken                       PSNHPINENTPPAILPIMRLALGSIMAGLLISSLILPPKTP

                              PTLTNINENNPTLLNPIKRLTIGSLFAGFFITNNILPMSTS

Xenopus laevis                NPLSPINENNKTVINPIKRLAWGSIVAGLLIASNMLPINSP

Zebrafish                     KTYETIDENHIPT-NTIQRLAWGSIIAGLIISYTMIPLKTP

Caenorhabditis elegans        ----VMNHYSSTVFMNFLSLVLVIFSISFLWWMNFNLLNIP

Drosophila                    GSLNMLNDESWIMLRGMMGLLIMSIIGGSMLNWLIFPFPY-

Slime mold                    KTIAGVHEASTNMVIPLVILALCSIFIGYVTKDFFVGLGTP

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 – 603 NADH-ubiquinone oxidoreductase chain 5
Transmembrane 458 – 478 Helical


Literature citations

Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy.
Brown M.D.; Voljavec A.S.; Lott M.T.; Torroni A.; Yang C.C.; Wallace D.C.;
Genetics 130:163-173(1992)
Cited for: VARIANT LHON THR-458;

Alternative, simultaneous complex I mitochondrial DNA mutations in Leber's hereditary optic neuropathy.
Johns D.R.; Berman J.;
Biochem. Biophys. Res. Commun. 174:1324-1330(1991)
Cited for: VARIANT LHON THR-458;

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.