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UniProtKB/Swiss-Prot P40939: Variant p.Glu510Gln

Trifunctional enzyme subunit alpha, mitochondrial
Gene: HADHA
Chromosomal location: 2p23
Variant information

Variant position:  510
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 Glutamate (E) to Glutamine (Q) at position 510 (E510Q, p.Glu510Gln).
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 acidic (E) to medium size and polar (Q)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  2
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:  Maternal acute fatty liver of pregnancy (AFLP) [MIM:609016]: Severe maternal illness occurring during pregnancies with affected fetuses. This disease is associated with LCHAD deficiency and characterized by sudden unexplained infant death or hypoglycemia and abnormal liver enzymes (Reye-like syndrome). {ECO:0000269|PubMed:7846063}. 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:  Long-chain 3-hydroxyl-CoA dehydrogenase deficiency (LCHAD deficiency) [MIM:609016]: The clinical features are very similar to TFP deficiency. Biochemically, LCHAD deficiency is characterized by reduced long-chain 3-hydroxyl-CoA dehydrogenase activity, while the other enzyme activities of the TFP complex are normal or only slightly reduced. {ECO:0000269|PubMed:7811722, ECO:0000269|PubMed:9266371}. 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 AFLP and LCHAD deficiency; loss of activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  510
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  763
The length of the canonical sequence.

Location on the sequence:   RPEKVIGMHYFSPVDKMQLL  E IITTEKTSKDTSASAVAVGL
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                         RPEKVIGMHYFSPVDKMQLLEIITTEKTSKDTSASAVAVGL

Mouse                         RPEKVIGMHYFSPVDKMQLLEIITTDKTSKDTTASAVAVGL

Rat                           RPEKVIGMHYFSPVDKMQLLEIITTDKTSKDTTASAVAVGL

Pig                           RPEKVIGMHYFSPVDKMQLLEIITTEKTSKDSTASAVEVGL

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 37 – 763 Trifunctional enzyme subunit alpha, mitochondrial
Modified residue 505 – 505 N6-acetyllysine; alternate
Modified residue 505 – 505 N6-succinyllysine; alternate
Modified residue 519 – 519 N6-acetyllysine; alternate
Modified residue 519 – 519 N6-succinyllysine; alternate
Alternative sequence 83 – 763 Missing. In isoform 2.


Literature citations

Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of the major disease-causing mutation in the alpha-subunit of the mitochondrial trifunctional protein.
Ijlst L.; Wanders R.J.A.; Ushikubo S.; Kamijo T.; Hashimoto T.;
Biochim. Biophys. Acta 1215:347-350(1994)
Cited for: VARIANT LCHAD DEFICIENCY GLN-510;

The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy.
Sims H.F.; Brackett J.C.; Powell C.K.; Treem W.R.; Hale D.E.; Bennett M.J.; Gibson B.; Shapiro S.; Strauss A.W.;
Proc. Natl. Acad. Sci. U.S.A. 92:841-845(1995)
Cited for: VARIANT AFLP GLN-510;

Common missense mutation G1528C in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Characterization and expression of the mutant protein, mutation analysis on genomic DNA and chromosomal localization of the mitochondrial trifunctional protein alpha subunit gene.
Ijlst L.; Ruiter J.P.N.; Hoovers J.M.N.; Jakobs M.E.; Wanders R.J.A.;
J. Clin. Invest. 98:1028-1033(1996)
Cited for: CHARACTERIZATION OF VARIANT LCHAD DEFICIENCY GLN-510;

Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of two new mutations.
Ijlst L.; Oostheim W.; Ruiter J.P.N.; Wanders R.J.A.;
J. Inherit. Metab. Dis. 20:420-422(1997)
Cited for: VARIANTS LCHAD DEFICIENCY PRO-342 AND GLN-510;

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.