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UniProtKB/Swiss-Prot O14521: Variant p.Gly12Ser

Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial
Gene: SDHD
Variant information

Variant position:  12
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 Glycine (G) to Serine (S) at position 12 (G12S, p.Gly12Ser).
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 small size and polar (S)
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

Variant description:  Polymorphism that may increase susceptibility for developing pheochromocytoma, paraganglioma, intestinal carcinoid tumor and breast, renal and uterus carcinoma; associated with increased manganese superoxide dismutase expression; associated with increased reactive oxygen species; associated with 1.9-fold increase in both AKT and MAPK expression.
Any additional useful information about the variant.

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



Sequence information

Variant position:  12
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  159
The length of the canonical sequence.

Location on the sequence:   MAVLWRLSAVC  G ALGGRALLLRTPVVRPAHIS
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                         MAVLWRLSAVCGALGGRALLLRTPVVRP--AHIS

Mouse                         MAVLLKLGVLCSGQGARALLLRSRVVRP--AY

Rat                           MAVLLKLGVLCSGQGARALSLRSRAVRP--AF

Pig                           MATLWRLSVLCGARGGGALVLRTSVVRP--AH

Bovine                        -MALWRLSVLCGAREGRALFLRTPVVRP--AL

Sheep                         -MALSRLSVLCGVREGRALFLRTPVVRP--AL

Chicken                       AALVLLRAGLARPRGVPTALLRGTLLRH----

Xenopus tropicalis            MATLLRVSSLC--RANRASAFKSLLIRP----

Caenorhabditis elegans        AASLRHMA-----HFQKALLVARSAPR-----

Drosophila                    SLSLLLRGAVRCNAANLVKSARITPLKSYSTL

Baker's yeast                 PRSMKFMTGRRIFHTATVRAFQSTAKKSLTIP

Fission yeast                 LQTRLGLGALR--QGRLLFAVKSFSTTS----

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
Transit peptide 1 – 56 Mitochondrion


Literature citations

Germline SDHD mutation in paraganglioma of the spinal cord.
Masuoka J.; Brandner S.; Paulus W.; Soffer D.; Vital A.; Chimelli L.; Jouvet A.; Yonekawa Y.; Kleihues P.; Ohgaki H.;
Oncogene 20:5084-5086(2001)
Cited for: VARIANT SER-12;

Alterations of the SDHD gene locus in midgut carcinoids, Merkel cell carcinomas, pheochromocytomas, and abdominal paragangliomas.
Kytoelae S.; Nord B.; Elder E.E.; Carling T.; Kjellman M.; Cedermark B.; Juhlin C.; Hoeoeg A.; Isola J.; Larsson C.;
Genes Chromosomes Cancer 34:325-332(2002)
Cited for: VARIANTS SER-12 AND ARG-50;

Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas.
Gimenez-Roqueplo A.-P.; Favier J.; Rustin P.; Rieubland C.; Crespin M.; Nau V.; Khau Van Kien P.; Corvol P.; Plouin P.-F.; Jeunemaitre X.;
Cancer Res. 63:5615-5621(2003)
Cited for: VARIANTS SER-12 AND ARG-50;

G12S and H50R variations are polymorphisms in the SDHD gene.
Cascon A.; Ruiz-Llorente S.; Cebrian A.; Leton R.; Telleria D.; Benitez J.; Robledo M.;
Genes Chromosomes Cancer 37:220-221(2003)
Cited for: DISCUSSION OF PATHOGENIC ROLE OF VARIANTS SER-12 AND ARG-50;

SDHD mutation analysis in seven German patients with sporadic carotid body paraganglioma: one novel mutation, no Dutch founder mutation and further evidence that G12S is a polymorphism.
Leube B.; Huber R.; Goecke T.O.; Sandmann W.; Royer-Pokora B.;
Clin. Genet. 65:61-63(2004)
Cited for: VARIANT SER-12;

Germline mutations and variants in the succinate dehydrogenase genes in Cowden and Cowden-like syndromes.
Ni Y.; Zbuk K.M.; Sadler T.; Patocs A.; Lobo G.; Edelman E.; Platzer P.; Orloff M.S.; Waite K.A.; Eng C.;
Am. J. Hum. Genet. 83:261-268(2008)
Cited for: VARIANTS SER-12; ARG-50 AND ASN-145; CHARACTERIZATION OF VARIANTS SER-12; ARG-50 AND ASN-145;

DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome.
Ley T.J.; Mardis E.R.; Ding L.; Fulton B.; McLellan M.D.; Chen K.; Dooling D.; Dunford-Shore B.H.; McGrath S.; Hickenbotham M.; Cook L.; Abbott R.; Larson D.E.; Koboldt D.C.; Pohl C.; Smith S.; Hawkins A.; Abbott S.; Locke D.; Hillier L.W.; Miner T.; Fulton L.; Magrini V.; Wylie T.; Glasscock J.; Conyers J.; Sander N.; Shi X.; Osborne J.R.; Minx P.; Gordon D.; Chinwalla A.; Zhao Y.; Ries R.E.; Payton J.E.; Westervelt P.; Tomasson M.H.; Watson M.; Baty J.; Ivanovich J.; Heath S.; Shannon W.D.; Nagarajan R.; Walter M.J.; Link D.C.; Graubert T.A.; DiPersio J.F.; Wilson R.K.;
Nature 456:66-72(2008)
Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-12;

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.