UniProtKB/Swiss-Prot P03905: Variant p.Arg340His

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

Variant position:  340
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 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 Arginine (R) to Histidine (H) at position 340 (R340H, p.Arg340His).
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 large size and basic (R) to medium size and polar (H)
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; primary mutation; almost no vision recovery; most frequent mutation; seems to have no effect on electron transfer activity of the complex in inner mitochondrial membrane preparations.
Any additional useful information about the variant.



Sequence information

Variant position:  340
The position of the amino-acid change on the UniProtKB canonical protein sequence.

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

Location on the sequence:   GLTSSLLFCLANSNYERTHS  R IMILSQGLQTLLPLMAFWWL
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                         GLTSSLLFCLAN-SNYERTHSRIMILSQGLQTLLPLMAFWWL

Gorilla                       GLTSSLLFCLAN-SNYERTHSRIMILSQGLQTLLPLMALWW

Chimpanzee                    GLTSSLLSCLAN-SNYERTHSRIMILSQGLQTLLPLMAFWW

Mouse                         GLTSSLLFCLAN-SNYERIHSRTMIMARGLQMVFPLMATWW

Rat                           GLTSSLLFCLAN-TNYERIHSRTMIMARGLQMIFPLMATWW

Pig                           GLTSSMLFCLAN-TNYERVHSRTMILARGLQTLLPLMATWW

Bovine                        GLTSSMLFCLAN-SNYERIHSRTMILARGLQTLLPLMATWW

Rabbit                        GLTSSLLFCLAN-SNYERIHSRTMLLARGLQTILPLMAAWW

Sheep                         GLTSSMLFCLAN-SNYERVHSRTMILARGLQTLLPLMAAWW

Cat                           GLTSSMLFCLAN-SNYERVHSRTMILARGLQTILPLMAAWW

Dog                           GLTSSMLFCLAN-SNYERIHSRTMILARGLQTLLPLMAAWW

Horse                         GLTSSMLFCLAN-SNYERTHSRTMILARGLQTLLPLMAAWW

Chicken                       GLTSSLLFCLAN-TNYERTHSRILILTRGLQPLLPLMSVWW

Xenopus laevis                GLTHSALCCLAKYQSYERTHSRALLLSRGLETILPLMGTWW

Zebrafish                     GLTSSALFCLAN-TSYERTHSRTMILARGLQMVLPLATVWW

Caenorhabditis elegans        GYTSTLMFYLIG-EFYHTSGSRMIYFMSSFFSSSMIMGILF

Drosophila                    GLCSSGLFCLAN-VSYERLGSRSMLINKGLLNFMPSMTLWW

Slime mold                    GVVSGGLFLCIG-VIYDRCKTRIVYAYNNLVHVMPIMAILF

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 – 459 NADH-ubiquinone oxidoreductase chain 4


Literature citations

Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy.
Wallace D.C.; Singh G.; Lott M.T.; Hodge J.A.; Schurr T.G.; Lezza A.M.; Elsas L.J. II; Nikoskelainen E.K.;
Science 242:1427-1430(1988)
Cited for: VARIANT LHON HIS-340;

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 HIS-340;

Detection of the G to A mitochondrial DNA mutation at position 11778 in German families with Leber's hereditary optic neuropathy.
Kormann B.A.; Schuster H.; Berninger T.A.; Leo-Kottler B.;
Hum. Genet. 88:98-100(1991)
Cited for: VARIANT LHON HIS-340;

Leber's hereditary optic neuropathy in Indonesia: two families with the mtDNA 11778G>A and 14484T>C mutations.
Sudoyo H.; Sitepu M.; Malik S.; Poesponegoro H.D.; Marzuki S.;
Hum. Mutat. Suppl. 1:S271-S274(1998)
Cited for: VARIANT LHON HIS-340;

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.