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UniProtKB/Swiss-Prot Q16134: Variant p.Leu127His

Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial
Gene: ETFDH
Variant information

Variant position:  127
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 Leucine (L) to Histidine (H) at position 127 (L127H, p.Leu127His).
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 hydrophobic (L) to medium size and polar (H)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Glutaric aciduria 2C (GA2C) [MIM:231680]: An autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. {ECO:0000269|PubMed:12359134, ECO:0000269|PubMed:12815589, ECO:0000269|PubMed:16527485, ECO:0000269|PubMed:17412732, ECO:0000269|PubMed:19249206, ECO:0000269|PubMed:20370797}. 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 GA2C.
Any additional useful information about the variant.

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



Sequence information

Variant position:  127
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  617
The length of the canonical sequence.

Location on the sequence:   AQIGAHTLSGACLDPGAFKE  L FPDWKEKGAPLNTPVTEDRF
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                         AQIGAHTLSGACLDPGAFKELFPDWKEK-----GAPLNTPVTEDRF

Mouse                         AQIGAHTLSGACLDPAAFKELFPDWKEK-----GAPLNTPV

Rat                           AQIGAHTLSGACLDPAAFKELFPDWKEK-----GAPLNTPV

Pig                           AHIGAHTLSGACLDPRAFEELFPDWKEK-----GAPLNTPV

Bovine                        AQIGAHTLSGACLDPRALQELFPDWKEK-----GAPLNTPV

Caenorhabditis elegans        SVIGGHTLSGAVIETRALDELIPNWKEL-----GAPVYQQV

Slime mold                    SEVGSHILSGAVMDPKALNELIPDWKEK-----GAPLITEV

Baker's yeast                 SVLGGQTVSGAILEPGVWKELFPDEKSDIGIPLPKELATLV

Fission yeast                 AEPGNHSVSGAVIQPTALDELLPNWRDD-----PPENCTAV

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 34 – 617 Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial
Intramembrane 109 – 130
Modified residue 132 – 132 N6-acetyllysine


Literature citations

ETFDH mutations, CoQ10 levels, and respiratory chain activities in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency.
Liang W.C.; Ohkuma A.; Hayashi Y.K.; Lopez L.C.; Hirano M.; Nonaka I.; Noguchi S.; Chen L.H.; Jong Y.J.; Nishino I.;
Neuromuscul. Disord. 19:212-216(2009)
Cited for: VARIANTS GA2C THR-84; HIS-127 AND LEU-175;

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.