UniProtKB/SwissProt variant VAR

Variant information

Variant position:

233

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

Type of variant:

US

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 Glycine (G) to Serine (S) at position 233 (G233S, p.Gly233Ser).

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:

In D2HGA1; unknown pathological significance; no effect on catalytic activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs374535734 [ dbSNP | Ensembl ]

Sequence information

Variant position:

233

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

Protein sequence length:

521

The length of the canonical sequence.

Location on the sequence:

FLRYGSLHGTVLGLEVVLAD G TVLDCLTSLRKDNTGYDLKQ

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                         FLRYGSLHGTVLGLEVVLADGTVLDCLTSLRKDNTGYDLKQ

Mouse                         FLRYGSLRGTVLGLEVVLADGTILNCLTSLRKDNTGYDLKQ

Rat                           FLRYGSLRGTVLGLEVVLADGTILNCLTSLRKDNTGYDLKQ

Bovine                        VLRYGSLRGTVLGLEVVLADGTVLNCLTSLRKDNTGYDLKQ

Zebrafish                     LLRYGSLRGTVLGLEVVLADGHVLNCLATLRKDNTGYDLKQ

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	14 – 521	D-2-hydroxyglutarate dehydrogenase, mitochondrial
Domain	96 – 275	FAD-binding PCMH-type

Literature citations

Evidence for genetic heterogeneity in D-2-hydroxyglutaric aciduria.
Kranendijk M.; Struys E.A.; Gibson K.M.; Wickenhagen W.V.; Abdenur J.E.; Buechner J.; Christensen E.; de Kremer R.D.; Errami A.; Gissen P.; Gradowska W.; Hobson E.; Islam L.; Korman S.H.; Kurczynski T.; Maranda B.; Meli C.; Rizzo C.; Sansaricq C.; Trefz F.K.; Webster R.; Jakobs C.; Salomons G.S.;
Hum. Mutat. 31:279-283(2010)
Cited for: VARIANTS D2HGA1 TRP-109; LYS-127; VAL-131; SER-147; THR-153; VAL-153; 169-GLN--ALA-521 DEL; TYR-172; LEU-189; VAL-205; VAL-231; SER-233; TYR-375; MET-399; 400-TYR--ALA-521 DEL; HIS-419; THR-426; ASP-439; ALA-444; VAL-446 AND ARG-477; CHARACTERIZATION OF VARIANTS D2HGA1 TRP-109; VAL-153; TYR-172; 400-TYR--ALA-521 DEL; HIS-419 AND THR-426; FUNCTION; CATALYTIC ACTIVITY;

Structure, substrate specificity, and catalytic mechanism of human D-2-HGDH and insights into pathogenicity of disease-associated mutations.
Yang J.; Zhu H.; Zhang T.; Ding J.;
Cell Discov. 7:3-3(2021)
Cited for: X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 51-521 IN COMPLEX WITH D-2-HYDROXYGLUTARATE; D-MALATE; D-LACTATE; L-2-HYDROXYGLUTARATE AND 2-OXOGLUTARATE; FUNCTION; CATALYTIC ACTIVITY; ZINC-BINDING SITES; BIOPHYSICOCHEMICAL PROPERTIES; MUTAGENESIS OF ARG-386; THR-390; LYS-401; HIS-434; HIS-441; ASN-443; GLU-475 AND HIS-476; CHARACTERIZATION OF VARIANTS D2HGA1 TRP-109; LYS-127; VAL-131; SER-147; THR-153; VAL-153; TYR-172; LEU-189; VAL-205; VAL-231; SER-233; TYR-375; MET-399; HIS-419; THR-426; ASP-439; ALA-444; VAL-446 AND ARG-477; CHARACTERIZATION OF VARIANT VAL-436;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q8N465: Variant p.Gly233Ser