UniProtKB/SwissProt variant VAR

Dehydrodolichyl diphosphate synthase complex subunit DHDDS
Gene: DHDDS
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Variant information Variant position:

42 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 Lysine (K) to Glutamate (E) at position 42 (K42E, p.Lys42Glu). 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 basic (K) to medium size and acidic (E) 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
Variant description:

In RP59; 5-fold reduction in catalytic activity and reduced affinity for FPP but not for IPP. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs147394623 [ dbSNP | Ensembl ]

Sequence information Variant position:

42 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

333 The length of the canonical sequence.
Location on the sequence:

AGPMPKHIAFIMDGNRRYAK K CQVERQEGHSQGFNKLAETL 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                         AGPMPKHIAFIMDGNRRYAKKCQVERQEGHSQGFNKLAETL

Mouse                         AGPVPKHIAFIMDGNRRYAKKCQVERQEGHTQGFNKLAETL

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	1 – 333	Dehydrodolichyl diphosphate synthase complex subunit DHDDS
Binding site	34 – 34
Binding site	34 – 34
Binding site	34 – 34
Binding site	35 – 35
Binding site	35 – 35
Binding site	37 – 37
Binding site	37 – 37
Binding site	38 – 38
Binding site	38 – 38
Mutagenesis	34 – 34	D -> AEN. Strongly reduced cis-prenyltransferase activity.
Mutagenesis	38 – 38	R -> H. Strongly reduced cis-prenyltransferase activity.
Helix	36 – 42

Literature citations
A conserved C-terminal RXG motif in the NgBR subunit of cis-prenyltransferase is critical for prenyltransferase activity.
Grabinska K.A.; Edani B.H.; Park E.J.; Kraehling J.R.; Sessa W.C.;
J. Biol. Chem. 292:17351-17361(2017)
Cited for: COFACTOR; SUBUNIT; CATALYTIC ACTIVITY; FUNCTION; CHARACTERIZATION OF VARIANT RP59 GLU-42; BIOPHYSICOCHEMICAL PROPERTIES; PATHWAY; ACTIVITY REGULATION; Whole-exome sequencing links a variant in DHDDS to retinitis pigmentosa.
Zuchner S.; Dallman J.; Wen R.; Beecham G.; Naj A.; Farooq A.; Kohli M.A.; Whitehead P.L.; Hulme W.; Konidari I.; Edwards Y.J.; Cai G.; Peter I.; Seo D.; Buxbaum J.D.; Haines J.L.; Blanton S.; Young J.; Alfonso E.; Vance J.M.; Lam B.L.; Pericak-Vance M.A.;
Am. J. Hum. Genet. 88:201-206(2011)
Cited for: VARIANT RP59 GLU-42; A missense mutation in DHDDS, encoding dehydrodolichyl diphosphate synthase, is associated with autosomal-recessive retinitis pigmentosa in Ashkenazi Jews.
Zelinger L.; Banin E.; Obolensky A.; Mizrahi-Meissonnier L.; Beryozkin A.; Bandah-Rozenfeld D.; Frenkel S.; Ben-Yosef T.; Merin S.; Schwartz S.B.; Cideciyan A.V.; Jacobson S.G.; Sharon D.;
Am. J. Hum. Genet. 88:207-215(2011)
Cited for: VARIANT RP59 GLU-42; TISSUE SPECIFICITY;

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.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q86SQ9: Variant p.Lys42Glu