UniProtKB/Swiss-Prot P03905: Variant p.Thr420Ala

NADH-ubiquinone oxidoreductase chain 4
Gene: MT-ND4
Chromosomal location: M
Variant information

Variant position:  420
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Threonine (T) to Alanine (A) at position 420 (T420A, p.Thr420Ala).
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 (T) to small size and hydrophobic (A)
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:  Detected in a patient with mitochondrial complex I deficiency; uncertain pathological significance.
Any additional useful information about the variant.

Sequence information

Variant position:  420
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  459
The length of the canonical sequence.

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                         MLVTALYSLYMF----------------TTTQWGSLTHHINNM-------------------KPSFTR------------ENTLMFMH

Gorilla                       MLITALYSLYMF----------------TTTQWGPLTHHIT

Chimpanzee                    MLITALYSLYMF----------------TTTQWGSLTHHIN

Mouse                         IIITGMYSMYMI----------------ITTQRGKLTNHMI

Rat                           IVITGMYSMYMI----------------ITTQRGKLTSHMN

Pig                           MMITALYSLYML----------------ITTQRGKYTHHIN

Bovine                        MVITALYSLYML----------------IMTQRGKYTYHIN

Rabbit                        VLITALYSLYML----------------STTQRGKFTYHTN

Sheep                         MVITALYSLYML----------------ITTQRGKHTHHIN

Cat                           IIITALYSLYML----------------IMTQRGKYTHHIK

Dog                           IIITALYSLYML----------------ITTQRGKYSHHIK

Horse                         ITITALYSLYML----------------ITTQRGKYTHHIN

Chicken                       TLLTASYTLYML----------------LSTQRGTLPSHIT

Xenopus laevis                TLLTASYSLYMF----------------LMTQRGMTPEHLN

Zebrafish                     TLITANYSLYMF----------------LTSQRGSIPEHIT

Caenorhabditis elegans        FVVSFYYSLFLI----------------TSSLMGKGYHNFN

Drosophila                    SFFSAAYTLYLY----------------SFSQHGKLFSGVY


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.

Chain 1 – 459 NADH-ubiquinone oxidoreductase chain 4

Literature citations

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: VARIANT ALA-420;

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.