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UniProtKB/Swiss-Prot P03886: Variant p.Ala52Thr

NADH-ubiquinone oxidoreductase chain 1
Gene: MT-ND1
Variant information

Variant position:  52
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 Alanine (A) to Threonine (T) at position 52 (A52T, p.Ala52Thr).
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

Involvement in disease:  Leber hereditary optic neuropathy (LHON) [MIM:535000]: A maternally inherited disease resulting in acute or subacute loss of central vision, due to optic nerve dysfunction. Cardiac conduction defects and neurological defects have also been described in some patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes. {ECO:0000269|PubMed:1417830, ECO:0000269|PubMed:1674640, ECO:0000269|PubMed:1900003, ECO:0000269|PubMed:1928099, ECO:0000269|PubMed:1959619, ECO:0000269|PubMed:2018041}. 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 LHON; primary mutation; medium severity; some vision recovery; 80% reduction in rotenone-sensitive and ubiquinone-dependent electron transfer activity, whereas the proximal NADH dehydrogenase activity of the complex is unaffected.
Any additional useful information about the variant.

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



Sequence information

Variant position:  52
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  318
The length of the canonical sequence.

Location on the sequence:   QLRKGPNVVGPYGLLQPFAD  A MKLFTKEPLKPATSTITLYI
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                         QLRKGPNVVGPYGLLQPFADAMKLFTKEPLKPATSTITLYI

Gorilla                       QLRKGPNVVGPYGLLQPFADAMKLFTKEPLKPSTSTITLYI

                              QLRKGPNIVGPYGLLQPIADAVKLFTKEPLRPLTSSMSMFI

Chimpanzee                    QLRKGPNIVGPYGLLQPFADAMKLFTKEPLKPSTSTITLYI

Mouse                         QLRKGPNIVGPYGILQPFADAMKLFMKEPMRPLTTSMSLFI

Rat                           QLRKGPNIVGPYGILQPFADAMKLFMKEPMRPLTTSMSLFI

Pig                           QLRKGPNVVGPYGLLQPIADALKLFTKEPLRPATSSISMFI

Bovine                        QLRKGPNVVGPYGLLQPIADAIKLFIKEPLRPATSSASMFI

Rabbit                        QLRKGPNIVGPYGLLQPIADAIKLFTKEPLRPLTSSPLLFI

Sheep                         QFRKGPNVVGPYGLLQPIADAIKLFIKEPLRPATSSISMFI

Cat                           QLRKGPNVVGPYGLLQPIADAVKLFTKEPLRPLTSSMLMFI

Horse                         QLRKGPNIVGPYGLLQPIADALKLFIKEPLQPLTSSTSMFI

Chicken                       QARKGPNIVGPFGLLQPVADGVKLFIKEPIRPSTSSPFLFI

Xenopus laevis                QHRKGPNIVGPTGLIQPIADGVKLFIKEPVRPSTSSQTMFL

Zebrafish                     QLRKGPNVMGPRGLLQSVADGVKLFIKEPIRPSMASPILFL

Caenorhabditis elegans        QNRLGPTKVTFMGLAQALLDGVKLLKKEQMTPLNSSEVSFL

Drosophila                    QIRKGPNKVGLMGIPQPFCDAIKLFTKEQTYPLLSNYLSYY

Slime mold                    QKRRGPNVVGFVGLLQPLADGLKLVLKETIIPIVADKLIYA

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 – 318 NADH-ubiquinone oxidoreductase chain 1


Literature citations

Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees.
Howell N.; Bindoff L.A.; McCullough D.A.; Kubacka I.; Poulton J.; Mackey D.; Taylor L.; Turnbull D.M.;
Am. J. Hum. Genet. 49:939-950(1991)
Cited for: VARIANT LHON THR-52;

A new mtDNA mutation associated with Leber hereditary optic neuroretinopathy.
Huoponen K.; Vilkki J.; Aula P.; Nikoskelainen E.K.; Savontaus M.L.;
Am. J. Hum. Genet. 48:1147-1153(1991)
Cited for: VARIANT LHON THR-52;

Electron transfer properties of NADH:ubiquinone reductase in the ND1/3460 and the ND4/11778 mutations of the Leber hereditary optic neuroretinopathy (LHON).
Majander A.; Huoponen K.; Savontaus M.-L.; Nikoskelainen E.; Wikstroem M.;
FEBS Lett. 292:289-292(1991)
Cited for: CHARACTERIZATION OF VARIANT LHON THR-52;

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.