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UniProtKB/Swiss-Prot P31040: Variant p.Gly555Glu

Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
Gene: SDHA
Chromosomal location: 5p15
Variant information

Variant position:  555
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 Glycine (G) to Glutamate (E) at position 555 (G555E, p.Gly555Glu).
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 glycine (G) to medium size and acidic (E)
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:  Cardiomyopathy, dilated 1GG (CMD1GG) [MIM:613642]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:20551992}. 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:  Mitochondrial complex II deficiency (MT-C2D) [MIM:252011]: A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations. Clinical features include psychomotor regression in infants, poor growth with lack of speech development, severe spastic quadriplegia, dystonia, progressive leukoencephalopathy, muscle weakness, exercise intolerance, cardiomyopathy. Some patients manifest Leigh syndrome or Kearns-Sayre syndrome. Note=The disease is caused by mutations affecting the gene represented in this entry. {ECO:0000269|PubMed:12794685}.
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 MT-C2D and CMD1GG.
Any additional useful information about the variant.

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



Sequence information

Variant position:  555
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  664
The length of the canonical sequence.

Location on the sequence:   GCGKISKLYGDLKHLKTFDR  G MVWNTDLVETLELQNLMLCA
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                         GCGKISKLYGDL-KHLKTFDRGMVWNTDLVETLELQNLMLCA

Mouse                         GCEKISQLYGDL-KHLKTFDRGMVWNTDLVETLELQNLMLC

Rat                           GCEKVSQLYGDL-QHLKTFDRGMVWNTDLVETLELQNLMLC

Pig                           GCEKILRLYGDL-QHLKTFDRGMVWNTDLVETLELQNLMLC

Bovine                        GCEKISSLYGDL-RHLKTFDRGMVWNTDLVETLELQNLMLC

Chicken                       GCEKLSQIYCDL-AHLKTFDRGIVWNTDLVETLELQNLMLC

Xenopus tropicalis            GCEKLSAINSTM-DDIKTFDRGIVWNTDLVETLELQNLMLC

Zebrafish                     GCVKMESVYKSM-DDIKTFDRGIVWNTDLVETLELQNLMLN

Caenorhabditis elegans        GVKVLSKLYKDQ-AHLNVADKGLVWNSDLIETLELQNLLIN

Drosophila                    GVNKMKEIYKQF-KDIKVVDRSLIWNSDLVETLELQNLLAN

Slime mold                    GVELIDKCARSLINDLKTTDRTMIWNTDLIESLELQNLMTQ

Baker's yeast                 GVRNITAVEKTF-DDVKTTDRSMIWNSDLVETLELQNLLTC

Fission yeast                 GVKNIARVDGTY-KDIGIRDRGLIWNTDLVEALELRNLLTC

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 43 – 664 Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
Modified residue 538 – 538 N6-acetyllysine; alternate
Modified residue 538 – 538 N6-succinyllysine; alternate
Modified residue 541 – 541 N6-acetyllysine
Modified residue 547 – 547 N6-acetyllysine; alternate
Modified residue 547 – 547 N6-succinyllysine; alternate
Modified residue 550 – 550 N6-acetyllysine


Literature citations

Homozygous Gly555Glu mutation in the nuclear-encoded 70 kDa flavoprotein gene causes instability of the respiratory chain complex II.
Van Coster R.; Seneca S.; Smet J.; Van Hecke R.; Gerlo E.; Devreese B.; Van Beeumen J.; Leroy J.G.; De Meirleir L.; Lissens W.;
Am. J. Med. Genet. A 120:13-18(2003)
Cited for: VARIANT MT-C2D GLU-555;

Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase.
Levitas A.; Muhammad E.; Harel G.; Saada A.; Caspi V.C.; Manor E.; Beck J.C.; Sheffield V.; Parvari R.;
Eur. J. Hum. Genet. 18:1160-1165(2010)
Cited for: VARIANT CMD1GG GLU-555;

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.