UniProtKB/SwissProt variant VAR

Variant information

Variant position:

92

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

Type of variant:

LP/P [Disclaimer]

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 Aspartate (D) to Tyrosine (Y) at position 92 (D92Y, p.Asp92Tyr).

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 acidic (D) to large size and aromatic (Y)

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 PGL1 and pheochromocytoma.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs80338845 [ dbSNP | Ensembl ]

Sequence information

Variant position:

92

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:

VSVLLLGLLPAAYLNPCSAM D YSLAAALTLHGHWGLGQVVT

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                         VSVLLLG--LLPAAYLNPCSA---MDYSLAAALTLHGHWGLGQVVT

Mouse                         VSVLLLG--LIPAGYLNPCSV---VDYSLAAALTLHSHWGL

Rat                           VSVLLLG--LIPAGYLNPCSV---VDYSLAAALTLHSHWGI

Pig                           VSVLLLG--LLPAAYLNPCSA---MDYSLAAALTLHGHWGI

Bovine                        VSVLLLG--LIPAAYLNPCSA---MDYSLAATLTLHSHWGI

Sheep                         VSVLLLG--LIPAAYLNPCSA---MDYSLAATLTLHSHWGI

Chicken                       VSALLLG--LLPAAYLYPGPA---VDYSLAAALTLHGHWGL

Xenopus tropicalis            LSVALLG--LLPAAYLYPGAA---MDYSLAAALTLHGHWGL

Caenorhabditis elegans        WAVGMLP--ILPASYFIHGPV---MDAVLTVALTLHIHWGI

Drosophila                    VSAGLLA--VIPAAFIAPSQV---LDALMAISVVIHTHWGV

Baker's yeast                 FALSVVP--LATTAMLTTGPLSTAADSFFSVMLLGYCYMEF

Fission yeast                 IAIAMVPQVMIPLFTGTSHPL---MDAALACTLITHAHLGF

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	57 – 159	Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial
Transmembrane	91 – 111	Helical
Metal binding	102 – 102	Iron (heme axial ligand); shared with SDHC
Alternative sequence	56 – 158	HSGSKAASLHWTSERVVSVLLLGLLPAAYLNPCSAMDYSLAAALTLHGHWGLGQVVTDYVHGDALQKAAKAGLLALSALTFAGLCYFNYHDVGICKAVAMLWK -> HWALDKLLLTMFMGMPCRKLPRQGFWHFQ. In isoform 3.

Literature citations

Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma.
Baysal B.E.; Ferrell R.E.; Willett-Brozick J.E.; Lawrence E.C.; Myssiorek D.; Bosch A.; van der Mey A.; Taschner P.E.M.; Rubinstein W.S.; Myers E.N.; Richard C.W. III; Cornelisse C.J.; Devilee P.; Devlin B.;
Science 287:848-851(2000)
Cited for: VARIANTS PGL1 LEU-81; TYR-92 AND LEU-102;

Nearly all hereditary paragangliomas in the Netherlands are caused by two founder mutations in the SDHD gene.
Taschner P.E.M.; Jansen J.C.; Baysal B.E.; Bosch A.; Rosenberg E.H.; Broecker-Vriends A.H.J.T.; van Der Mey A.G.L.; van Ommen G.-J.B.; Cornelisse C.J.; Devilee P.;
Genes Chromosomes Cancer 31:274-281(2001)
Cited for: VARIANTS PGL1 TYR-92 AND PRO-139;

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: VARIANT PHEOCHROMOCYTOMA TYR-92;

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 PGL1 LEU-81; CYS-114 AND VAL-148; VARIANT PHEOCHROMOCYTOMA TYR-92;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O14521: Variant p.Asp92Tyr