UniProtKB/Swiss-Prot P21912: Variant p.Cys192Arg

Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial
Gene: SDHB
Chromosomal location: 1p35.2
Variant information

Variant position:  192
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 Cysteine (C) to Arginine (R) at position 192 (C192R, p.Cys192Arg).
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 polar (C) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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 pheochromocytoma.
Any additional useful information about the variant.



Sequence information

Variant position:  192
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  280
The length of the canonical sequence.

Location on the sequence:   QSIEEREKLDGLYECILCAC  C STSCPSYWWNGDKYLGPAVL
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                         QSIEEREKLDGLYECILCACCSTSCPSYWWNGDK---YLGPAVL

Mouse                         QSIEDREKLDGLYECILCACCSTSCPSYWWNGDK---YLGP

Rat                           QSIEDREKLDGLYECILCACCSTSCPSYWWNGDK---YLGP

Pig                           QSIEEREKLDGLYECILCACCSTSCPSYWWNGDK---YLGP

Bovine                        QSIEDREKLDGLYECILCACCSTSCPSYWWNGDK---YLGP

Chicken                       QSIEDRQKLDGLYECILCACCSTSCPSYWWNGDK---YLGP

Xenopus laevis                QSIEDRDKLDGLYECILCACCSTSCPSYWWNADK---YLGP

Xenopus tropicalis            QSIEDRDKLDGLYECILCACCSTSCPSYWWNADK---YLGP

Zebrafish                     QSVEDRQKLDGLYECILCACCSTSCPSYWWNADK---YLGP

Caenorhabditis elegans        QSVAERDRLDGLYECILCACCSTSCPSYWWNADK---YLGP

Drosophila                    QSVEDRSKLDGLYECILCACCSTSCPSYWWNAEK---YLGP

Slime mold                    QSKENRHKLDGLYECILCACCSTSCPSYWWSEGGDGGYLGP

Baker's yeast                 QSIEDRKKLDGLYECILCACCSTSCPSYWWNQEQ---YLGP

Fission yeast                 QSRADRAKLDGLYECILCACCSTSCPSYWWNSEE---YLGP

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 29 – 280 Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial
Domain 176 – 206 4Fe-4S ferredoxin-type
Metal binding 186 – 186 Iron-sulfur 2 (4Fe-4S)
Metal binding 189 – 189 Iron-sulfur 2 (4Fe-4S)
Metal binding 192 – 192 Iron-sulfur 2 (4Fe-4S)
Metal binding 196 – 196 Iron-sulfur 3 (3Fe-4S)
Binding site 201 – 201 Ubiquinone; shared with DHSD


Literature citations

Germ-line mutations in nonsyndromic pheochromocytoma.
Neumann H.P.H.; Bausch B.; McWhinney S.R.; Bender B.U.; Gimm O.; Franke G.; Schipper J.; Klisch J.; Altehoefer C.; Zerres K.; Januszewicz A.; Smith W.M.; Munk R.; Manz T.; Glaesker S.; Apel T.W.; Treier M.; Reineke M.; Walz M.K.; Hoang-Vu C.; Brauckhoff M.; Klein-Franke A.; Klose P.; Schmidt H.; Maier-Woelfle M.; Peczkowska M.; Szmigielski C.; Eng C.;
N. Engl. J. Med. 346:1459-1466(2002)
Cited for: VARIANTS PHEOCHROMOCYTOMA GLN-29 INS; GLY-46; TYR-101; ARG-192; TYR-196 AND HIS-242;

Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations.
Neumann H.P.H.; Pawlu C.; Peczkowska M.; Bausch B.; McWhinney S.R.; Muresan M.; Buchta M.; Franke G.; Klisch J.; Bley T.A.; Hoegerle S.; Boedeker C.C.; Opocher G.; Schipper J.; Januszewicz A.; Eng C.;
JAMA 292:943-951(2004)
Cited for: VARIANTS PHEOCHROMOCYTOMA GLY-46; GLN-46; ARG-53; PRO-65; SER-87; TYR-101; ARG-192; TYR-196 AND HIS-242; VARIANTS PGL4 GLN-46 AND HIS-242;

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.