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UniProtKB/Swiss-Prot P03897: Variant p.Ala47Thr

NADH-ubiquinone oxidoreductase chain 3
Gene: MT-ND3
Variant information

Variant position:  47
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 47 (A47T, p.Ala47Thr).
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:  Mitochondrial complex I deficiency, mitochondrial type 1 (MC1DM1) [MIM:500014]: A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. {ECO:0000269|PubMed:11456298, ECO:0000269|PubMed:14705112, ECO:0000269|PubMed:20818383}. 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.

Involvement in disease:  Leigh syndrome (LS) [MIM:256000]: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. {ECO:0000269|PubMed:17152068}. 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 LS and MC1DM1.
Any additional useful information about the variant.

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



Sequence information

Variant position:  47
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  115
The length of the canonical sequence.

Location on the sequence:   LNGYMEKSTPYECGFDPMSP  A RVPFSMKFFLVAITFLLFDL
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                         LNGYMEKSTPYECGFDPMSPARVPFSMKFFLVAITFLLFDL

Gorilla                       LNSYMEKTNPYECGFDPVSPARIPFSMKFFLVAITFLLFDL

                              LNIYTDKTSPYECGFDPMGSARLPFSMKFFLVAITFLLFDL

Chimpanzee                    LNSYMEKSTPYECGFDPMSPARVPFSMKFFLVAITFLLFDL

Mouse                         MNLYSEKANPYECGFDPTSSARLPFSMKFFLVAITFLLFDL

Rat                           MNLYSEKANPYECGFDPTSSARLPFSMKFFLVAITFLLFDL

Pig                           LNAYSEKTSPYECGFDPMGSARLPFSMKFFLVAITFLLFDL

Bovine                        LNVYSEKTSPYECGFDPMGSARLPFSMKFFLVAITFLLFDL

Rabbit                        LNIYSEKSSPYECGFDPMGSARLPFSMKFFLVAITFLLFDL

Sheep                         LNVYSEKTSPYECGFDPMGSARLPFSMKFFLVAITFLLFDL

Cat                           LNIYAEKASPYECGFDPMGSARLPFSMKFFLVAITFLLFDL

Horse                         LNIYAEKTSPYECGFDPMGSARLPFSMKFFLVAITFLLFDL

Chicken                       MAPDTEKLSPYECGFDPLGSARLPFSIRFFLVAILFLLFDL

Xenopus laevis                MTPDMEKLSPYECGFDPLGSMRLPFSMRFFLIAILFLLFDL

Zebrafish                     MNSDTEKLSPYECGFDPLGSARLPFSLRFFLVAVLFPLFDL

Caenorhabditis elegans        KDMGKNKISAFECGFVSVGKIQNSFSIHFFIMMLMFVIFDL

Drosophila                    ALIDREKSSPFECGFDPKSSSRLPFSLRFFLITIIFLIFDV

Slime mold                    KVAYEDKLMGYECGFDPFGNARGEFDIRFYLVAILFLIFDL

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 – 115 NADH-ubiquinone oxidoreductase chain 3


Literature citations

A novel recurrent mitochondrial DNA mutation in ND3 gene is associated with isolated complex I deficiency causing Leigh syndrome and dystonia.
Sarzi E.; Brown M.D.; Lebon S.; Chretien D.; Munnich A.; Rotig A.; Procaccio V.;
Am. J. Med. Genet. A 143:33-41(2007)
Cited for: VARIANT LS THR-47;

High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency.
Calvo S.E.; Tucker E.J.; Compton A.G.; Kirby D.M.; Crawford G.; Burtt N.P.; Rivas M.; Guiducci C.; Bruno D.L.; Goldberger O.A.; Redman M.C.; Wiltshire E.; Wilson C.J.; Altshuler D.; Gabriel S.B.; Daly M.J.; Thorburn D.R.; Mootha V.K.;
Nat. Genet. 42:851-858(2010)
Cited for: VARIANTS MC1DM1 PRO-34; PRO-45 AND THR-47;

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.