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UniProtKB/Swiss-Prot P09622: Variant p.Arg482Gly

Dihydrolipoyl dehydrogenase, mitochondrial
Gene: DLD
Variant information

Variant position:  482
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 Arginine (R) to Glycine (G) at position 482 (R482G, p.Arg482Gly).
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 glycine (G)
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

Variant description:  In DLDD; reduced enzyme activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  482
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:   EMVNEAALALEYGASCEDIA  R VCHAHPTLSEAFREANLAAS
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                         EMVNEAALALEYGASCEDIARVCHAHPTLSEAFREANLAAS

                              EMVNEAALALEYGASCEDIARVCHAHPTLSEAFREANLAAS

Mouse                         EMVNEAALALEYGASCEDIARVCHAHPTLSEAFREANLAAA

Rat                           EMVNEAALALEYGASCEDVARVCHAHPTLSEAFREANLAAS

Pig                           EMINEAALALEYGASCEDIARVCHAHPTLSEAFREANLAAS

Caenorhabditis elegans        EMIAEATLAMEYGASAEDVARVCHPHPTLSEAFREANLAAY

Slime mold                    ELIGECVLAMEYGASCEDIARTCHGHPTLSEAVKEAAMDAY

Baker's yeast                 EMIAEAGLALEYGASAEDVARVCHAHPTLSEAFKEANMAAY

Fission yeast                 ELIGEATLALEYGASAEDVARVCHAHPTLSEATKEAMMAAW

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
Active site 487 – 487 Proton acceptor
Site 473 – 473 Important for interaction with PDHX and activity of multienzyme pyruvate dehydrogenase complex
Modified residue 502 – 502 Phosphoserine
Mutagenesis 466 – 466 E -> A. Decreases dehydrogenase activity. Loss of proteolytic activity.
Mutagenesis 473 – 473 Y -> A. Reduces interaction with PDHX. Inhibits multienzyme pyruvate dehydrogenase complex activity. Does not affect dihydrolipoyl dehydrogenase activity.
Mutagenesis 473 – 473 Y -> F. Does not affect dihydrolipoyl dehydrogenase activity.
Mutagenesis 473 – 473 Y -> H. Reduces interaction with PDHX. Inhibits multienzyme pyruvate dehydrogenase complex activity. Does not affect dihydrolipoyl dehydrogenase activity.
Mutagenesis 482 – 482 R -> A. Does not affect dihydrolipoyl dehydrogenase activity.
Mutagenesis 482 – 482 R -> M. Does not affect interaction with PDHX.
Mutagenesis 485 – 485 H -> A. Loss of dehydrogenase activity. Increases proteolytic activity.
Mutagenesis 491 – 491 S -> A. Loss of proteolytic activity. Does not affect dehydrogenase activity.
Mutagenesis 492 – 492 E -> Q. Reduces dihydrolipoyl dehydrogenase activity. Does not affect interaction with PDHX.
Helix 477 – 482


Literature citations

A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency.
Odievre M.H.; Chretien D.; Munnich A.; Robinson B.H.; Dumoulin R.; Masmoudi S.; Kadhom N.; Roetig A.; Rustin P.; Bonnefont J.P.;
Hum. Mutat. 25:323-324(2005)
Cited for: VARIANT DLDD GLY-482; CHARACTERIZATION OF VARIANT DLDD GLY-482; 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.