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UniProtKB/Swiss-Prot P21912: Variant p.Arg242His

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

Variant position:  242
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Arginine (R) to Histidine (H) at position 242 (R242H, p.Arg242His).
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 medium size and polar (H)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Paragangliomas 4 (PGL4) [MIM:115310]: A neural crest tumor usually derived from the chromoreceptor tissue of a paraganglion. Paragangliomas can develop at various body sites, including the head, neck, thorax and abdomen. Most commonly, they are located in the head and neck region, specifically at the carotid bifurcation, the jugular foramen, the vagal nerve, and in the middle ear. {ECO:0000269|PubMed:11404820, ECO:0000269|PubMed:11897817, ECO:0000269|PubMed:14715873, ECO:0000269|PubMed:14974914, ECO:0000269|PubMed:15328326}. 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:  Pheochromocytoma (PCC) [MIM:171300]: A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. {ECO:0000269|PubMed:11404820, ECO:0000269|PubMed:12000816, ECO:0000269|PubMed:12618761, ECO:0000269|PubMed:14500403, ECO:0000269|PubMed:14974914, ECO:0000269|PubMed:15328326, ECO:0000269|PubMed:17634472}. Note=Disease susceptibility is associated with variations 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.

Variant description:  In PGL4 and PCC.
Any additional useful information about the variant.

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



Sequence information

Variant position:  242
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:   SRDDFTEERLAKLQDPFSLY  R CHTIMNCTRTCPKGLNPGKA
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                         SRDDFTEERLAKL-QDPFSLYRCHTIMNCTRTCPKGLNPGKA

Mouse                         SRDDFTEERLAKL-QDPFSVYRCHTIMNCTQTCPKGLNPGK

Rat                           SRDEFTEERLAKL-QDPFSLYRCHTIMNCTQTCPKGLNPGK

Pig                           SRDDFTEERLAKL-QDPFSLYRCHTIMNCTGTCPKGLNPGK

Bovine                        SRDDFTEERLAKL-QDPFSLYRCHTIMNCTQTCPKGLNPGK

Chicken                       SRDDYTEERLAQL-QDPFSLYRCHTIMNCTRTCPKGLNPGK

Xenopus laevis                SRDDFTEERLSKL-QDPFSLYRCHTIMNCTRTCPKGLNPGK

Xenopus tropicalis            SRDDYTEERLAKL-QDPFSLYRCHTIMNCTRTCPKGLNPGK

Zebrafish                     SRDDFTEDRLSKL-QDPFSLYRCHTIMNCTRTCPKGLNPGK

Caenorhabditis elegans        SRDDYATERLHRM-HDSFSAFKCHTIMNCTKTCPKHLNPAK

Drosophila                    SRDENSAERLNKL-KDPFSVYRCHTIMNCTRTCPKGLNPGR

Slime mold                    SRDSIQKDRLAILSEDQMKVYKCHTIMNCTAVCPKGLNPGK

Baker's yeast                 SRDQATKTRKAML-NNSMSLYRCHTIMNCTRTCPKGLNPGL

Fission yeast                 SRDQATAKRLDVM-QNSMSVYRCHTIMNCARTCPKGLNPGL

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
Metal binding 243 – 243 Iron-sulfur 3 (3Fe-4S)
Metal binding 249 – 249 Iron-sulfur 3 (3Fe-4S)
Metal binding 253 – 253 Iron-sulfur 2 (4Fe-4S)


Literature citations

Familial malignant catecholamine-secreting paraganglioma with prolonged survival associated with mutation in the succinate dehydrogenase B gene.
Young A.L.; Baysal B.E.; Deb A.; Young W.F. Jr.;
J. Clin. Endocrinol. Metab. 87:4101-4105(2002)
Cited for: VARIANT FAMILIAL MALIGNANT PARAGANGLIOMA HIS-242;

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 PCC 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 PCC 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.