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:

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 Aspartate (D) to Glycine (G) at position 92 (D92G, p.Asp92Gly).

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 glycine (G)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-1

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:

Mitochondrial complex II deficiency (MT-C2D) [MIM:252011]: A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations. Clinical features include psychomotor regression in infants, poor growth with lack of speech development, severe spastic quadriplegia, dystonia, progressive leukoencephalopathy, muscle weakness, exercise intolerance, cardiomyopathy. Some patients manifest Leigh syndrome or Kearns-Sayre syndrome. {ECO:0000269|PubMed:24367056, ECO:0000269|PubMed:26008905}. 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 MT-C2D; results in highly reduced protein expression; results in impaired cellular respiration.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs786205436 [ 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

A recessive homozygous p.Asp92Gly SDHD mutation causes prenatal cardiomyopathy and a severe mitochondrial complex II deficiency.
Alston C.L.; Ceccatelli Berti C.; Blakely E.L.; Olahova M.; He L.; McMahon C.J.; Olpin S.E.; Hargreaves I.P.; Nolli C.; McFarland R.; Goffrini P.; O'Sullivan M.J.; Taylor R.W.;
Hum. Genet. 134:869-879(2015)
Cited for: VARIANT MT-C2D GLY-92; INVOLVEMENT IN MT-C2D; CHARACTERIZATION OF VARIANT MT-C2D GLY-92;

UniProtKB/Swiss-Prot O14521: Variant p.Asp92Gly