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UniProtKB/Swiss-Prot P09622: Variant p.Glu375Lys

Dihydrolipoyl dehydrogenase, mitochondrial
Gene: DLD
Variant information

Variant position:  375
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Glutamate (E) to Lysine (K) at position 375 (E375K, p.Glu375Lys).
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 large size and basic (K)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
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 DLDD; loss of enzyme activity; abolished interaction with PDHX.
Any additional useful information about the variant.

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



Sequence information

Variant position:  375
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  509
The length of the canonical sequence.

Location on the sequence:   DVVAGPMLAHKAEDEGIICV  E GMAGGAVHIDYNCVPSVIYT
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                         DVVAGPMLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYT

                              DVVAGPMLAHKAEDEGIICVEGMAGGAVPIDYNCVPSVIYT

Mouse                         DVVAGPMLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYT

Rat                           DVVAGPMLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYT

Pig                           DVVAGPMLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYT

Caenorhabditis elegans        DVIEGPMLAHKAEDEGILCVEGIAGGPVHIDYNCVPSVVYT

Slime mold                    DAIRGPMLAHKAEEEGIAIIEQIHNGGGHVNYGAIPSIIYT

Baker's yeast                 DVTFGPMLAHKAEEEGIAAVEMLKTGHGHVNYNNIPSVMYS

Fission yeast                 DATLGPMLAHKAEDEGIAAVEYIAKGQGHVNYNCIPAVMYT

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 36 – 509 Dihydrolipoyl dehydrogenase, mitochondrial
Binding site 355 – 355 FAD
Mutagenesis 383 – 383 H -> A. Reduces dihydrolipoyl dehydrogenase activity.
Mutagenesis 383 – 383 H -> L. Reduces dihydrolipoyl dehydrogenase activity.
Helix 363 – 377


Literature citations

Interaction of E1 and E3 components with the core proteins of the human pyruvate dehydrogenase complex.
Patel M.S.; Korotchkina L.G.; Sidhu S.;
J. Mol. Catal., B Enzym. 61:2-6(2009)
Cited for: CATALYTIC ACTIVITY; INTERACTION WITH PDHX; MUTAGENESIS OF LYS-89; ARG-482; GLU-492 AND LYS-505; CHARACTERIZATION OF VARIANTS DLDD GLU-72; LYS-375; LEU-488 AND GLY-495;

Deficiency of dihydrolipoamide dehydrogenase due to two mutant alleles (E340K and G101del). Analysis of a family and prenatal testing.
Hong Y.S.; Kerr D.S.; Liu T.C.; Lusk M.; Powell B.R.; Patel M.S.;
Biochim. Biophys. Acta 1362:160-168(1997)
Cited for: VARIANTS DLDD GLY-136 DEL AND LYS-375;

Novel mutations in a boy with dihydrolipoamide dehydrogenase deficiency.
Cerna L.; Wenchich L.; Hansikova H.; Kmoch S.; Peskova K.; Chrastina P.; Brynda J.; Zeman J.;
Med. Sci. Monit. 7:1319-1325(2001)
Cited for: VARIANTS DLDD VAL-361 AND LYS-375;

Novel mutations in dihydrolipoamide dehydrogenase deficiency in two cousins with borderline-normal PDH complex activity.
Cameron J.M.; Levandovskiy V.; Mackay N.; Raiman J.; Renaud D.L.; Clarke J.T.; Feigenbaum A.; Elpeleg O.; Robinson B.H.;
Am. J. Med. Genet. A 140:1542-1552(2006)
Cited for: VARIANTS DLDD THR-47; CYS-229 AND LYS-375; CATALYTIC ACTIVITY;

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.