UniProtKB/SwissProt variant VAR

Variant information

Variant position:

114

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 Tyrosine (Y) to Cysteine (C) at position 114 (Y114C, p.Tyr114Cys).

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 aromatic (Y) to medium size and polar (C)

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

Involvement in disease:

Paragangliomas 1 (PGL1) [MIM:168000]: A neural crest tumor usually derived from the chromoreceptor tissue of a paraganglion. PGL1 is a rare autosomal dominant disorder which is characterized by the development of mostly benign, highly vascular, slowly growing tumors in the head and neck. In the head and neck region, the carotid body is the largest of all paraganglia and is also the most common site of the tumors. {ECO:0000269|PubMed:10657297, ECO:0000269|PubMed:11343322, ECO:0000269|PubMed:11391796, ECO:0000269|PubMed:11391798, 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.

Variant description:

In PGL1.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104894304 [ dbSNP | Ensembl ]

Sequence information

Variant position:

114

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:

SLAAALTLHGHWGLGQVVTD Y VHGDALQKAAKAGLLALSAL

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                         SLAAALTLHGHWGLGQVVTDY----VHGDALQKAAKAGLLALSAL

Mouse                         SLAAALTLHSHWGLGQVVTDY----VHGDTLPKAARAGLLA

Rat                           SLAAALTLHSHWGIGQVVTDY----VHGDALQKATKAGLLA

Pig                           SLAAALTLHGHWGIGQVVTDY----VRGDALQKVAKAGLLA

Bovine                        SLAATLTLHSHWGIGQVVTDY----VHGDAVQKAAKTGLLV

Sheep                         SLAATLTLHSHWGIGQVVTDY----VHGDAVQKAAKTGLLV

Chicken                       SLAAALTLHGHWGLGQVITDY----VHGDTPIKVANTGLYV

Xenopus tropicalis            SLAAALTLHGHWGLGQVVTDY----VHGDAKIKMANTSLFA

Caenorhabditis elegans        VLTVALTLHIHWGIHGVVYDYARPYVIGEAAAKAAHVGVYL

Drosophila                    LMAISVVIHTHWGVEAMVVDYMRPSVVGNVLPKVAHIALII

Baker's yeast                 FFSVMLLGYCYMEFNSCITDYISERVYG-VWHKYAMYMLGL

Fission yeast                 ALACTLITHAHLGFESCVIDYFPARRFK-KLSPLMHWILRG

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
Topological domain	112 – 120	Mitochondrial matrix
Metal binding	102 – 102	Iron (heme axial ligand); shared with SDHC
Binding site	114 – 114	Ubiquinone; shared with IP/SDHB
Alternative sequence	56 – 158	HSGSKAASLHWTSERVVSVLLLGLLPAAYLNPCSAMDYSLAAALTLHGHWGLGQVVTDYVHGDALQKAAKAGLLALSALTFAGLCYFNYHDVGICKAVAMLWK -> HWALDKLLLTMFMGMPCRKLPRQGFWHFQ. In isoform 3.
Alternative sequence	106 – 143	GLGQVVTDYVHGDALQKAAKAGLLALSALTFAGLCYFN -> LECNGAILARHDLGSARSQLTATSAFRVQAILLPQPPK. In isoform 4.

Literature citations

Novel mutations and the emergence of a common mutation in the SDHD gene causing familial paraganglioma.
Milunsky J.M.; Maher T.A.; Michels V.V.; Milunsky A.;
Am. J. Med. Genet. 100:311-314(2001)
Cited for: VARIANT PGL1 CYS-114;

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 O14521: Variant p.Tyr114Cys