UniProtKB/Swiss-Prot A6NFY7: Variant p.Gly57Arg

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 57 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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 Glycine (G) to Arginine (R) at position 57 (G57R, p.Gly57Arg). 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 large size and basic (R) 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 MC2DN2; abolishes binding to the iron-sulfur transfer complex formed by HSC20, HSPA9 and ICSU; prevents interaction with SDHB; leads to rapid degradation of SDHAF1. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs137853192 [ dbSNP | Ensembl ]

Sequence information

Variant position: 57 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 115 The length of the canonical sequence.
Location on the sequence: RQHAGLPRSDVLRIEYLYRR G RRQLQLLRSGHATAMGAFVR 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.
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.

Type	Positions	Description
Chain	1 – 115	Succinate dehydrogenase assembly factor 1, mitochondrial
Region	53 – 65	Interaction with SDHB

Literature citations

SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy.
Ghezzi D.; Goffrini P.; Uziel G.; Horvath R.; Klopstock T.; Lochmuller H.; D'Adamo P.; Gasparini P.; Strom T.M.; Prokisch H.; Invernizzi F.; Ferrero I.; Zeviani M.;
Nat. Genet. 41:654-656(2009)
Cited for: VARIANTS MC2DN2 PRO-55 AND ARG-57; FUNCTION; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; Leukoencephalopathy with accumulated succinate is indicative of SDHAF1 related complex II deficiency.
Ohlenbusch A.; Edvardson S.; Skorpen J.; Bjornstad A.; Saada A.; Elpeleg O.; Gaertner J.; Brockmann K.;
Orphanet J. Rare Dis. 7:69-69(2012)
Cited for: VARIANTS MC2DN2 8-GLN--ARG-115 DEL; PRO-55 AND ARG-57; Magnetic resonance imaging spectrum of succinate dehydrogenase-related infantile leukoencephalopathy.
Helman G.; Caldovic L.; Whitehead M.T.; Simons C.; Brockmann K.; Edvardson S.; Bai R.; Moroni I.; Taylor J.M.; Van Haren K.; Taft R.J.; Vanderver A.; van der Knaap M.S.;
Ann. Neurol. 79:379-386(2016)
Cited for: VARIANTS MC2DN2 8-GLN--ARG-115 DEL; 52-TYR--ARG-115 DEL; PRO-55; ARG-57 AND GLU-57; Disease-causing SDHAF1 mutations impair transfer of Fe-S clusters to SDHB.
Maio N.; Ghezzi D.; Verrigni D.; Rizza T.; Bertini E.; Martinelli D.; Zeviani M.; Singh A.; Carrozzo R.; Rouault T.A.;
Cell Metab. 23:292-302(2016)
Cited for: CHARACTERIZATION OF VARIANTS MC2DN2 PRO-55 AND ARG-57; VARIANT MC2DN2 35-GLU--ARG-115 DEL; FUNCTION; INTERACTION WITH HSC20 AND SDHB; ROLE OF LYR MOTIFS; MUTAGENESIS OF 14-LYS--ARG-16 AND 53-LYS--ARG-55;