UniProtKB/SwissProt variant VAR

Variant information

Variant position:

258

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 Serine (S) to Leucine (L) at position 258 (S258L, p.Ser258Leu).

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 small size and polar (S) to medium size and hydrophobic (L)

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

Variant description:

In CDG1K; decreased function in protein glycosylation as shown by rescue assays in an ALG1-deficient yeast strain.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs28939378 [ dbSNP | Ensembl ]

Sequence information

Variant position:

258

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

Protein sequence length:

464

The length of the canonical sequence.

Location on the sequence:

GSMHSPFRARSEPEDPVTER S AFTERDAGSGLVTRLRERPA

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                         GSMHSPFRARSEPEDPVTERSAFTERDAGSGLVTRLRERPA

Mouse                         SHTYSPFQSCSDPSHPDTERSAFTERDCQSGVVRRLHGRPA

Slime mold                    -TFINKY-------SIKGEDKVYIESVISKKSIRNPKQQTS

Baker's yeast                 KAFIKNYIR----DDFDTEKG------------------DK

Fission yeast                 KKIPCEY-------NPSS---------------------TK

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 – 464	Chitobiosyldiphosphodolichol beta-mannosyltransferase
Topological domain	24 – 464	Lumenal
Region	243 – 262	Disordered
Compositional bias	245 – 259	Basic and acidic residues
Modified residue	242 – 242	Phosphoserine

Literature citations

Deficiency of GDP-Man:GlcNAc2-PP-dolichol mannosyltransferase causes congenital disorder of glycosylation type Ik.
Schwarz M.; Thiel C.; Luebbehusen J.; Dorland B.; de Koning T.; von Figura K.; Lehle L.; Koerner C.;
Am. J. Hum. Genet. 74:472-481(2004)
Cited for: VARIANT CDG1K LEU-258; FUNCTION; CATALYTIC ACTIVITY; PATHWAY;

Congenital disorder of glycosylation type Ik (CDG-Ik): a defect of mannosyltransferase I.
Kranz C.; Denecke J.; Lehle L.; Sohlbach K.; Jeske S.; Meinhardt F.; Rossi R.; Gudowius S.; Marquardt T.;
Am. J. Hum. Genet. 74:545-551(2004)
Cited for: VARIANTS CDG1K LEU-258 AND PRO-342;

Deficiency of the first mannosylation step in the N-glycosylation pathway causes congenital disorder of glycosylation type Ik.
Grubenmann C.E.; Frank C.G.; Huelsmeier A.J.; Schollen E.; Matthijs G.; Mayatepek E.; Berger E.G.; Aebi M.; Hennet T.;
Hum. Mol. Genet. 13:535-542(2004)
Cited for: VARIANTS CDG1K ARG-150 AND LEU-258; VARIANT GLU-429;

ALG1-CDG: Clinical and Molecular Characterization of 39 Unreported Patients.
Ng B.G.; Shiryaev S.A.; Rymen D.; Eklund E.A.; Raymond K.; Kircher M.; Abdenur J.E.; Alehan F.; Midro A.T.; Bamshad M.J.; Barone R.; Berry G.T.; Brumbaugh J.E.; Buckingham K.J.; Clarkson K.; Cole F.S.; O'Connor S.; Cooper G.M.; Van Coster R.; Demmer L.A.; Diogo L.; Fay A.J.; Ficicioglu C.; Fiumara A.; Gahl W.A.; Ganetzky R.; Goel H.; Harshman L.A.; He M.; Jaeken J.; James P.M.; Katz D.; Keldermans L.; Kibaek M.; Kornberg A.J.; Lachlan K.; Lam C.; Yaplito-Lee J.; Nickerson D.A.; Peters H.L.; Race V.; Regal L.; Rush J.S.; Rutledge S.L.; Shendure J.; Souche E.; Sparks S.E.; Trapane P.; Sanchez-Valle A.; Vilain E.; Voello A.; Waechter C.J.; Wang R.Y.; Wolfe L.A.; Wong D.A.; Wood T.; Yang A.C.; Matthijs G.; Freeze H.H.;
Hum. Mutat. 37:653-660(2016)
Cited for: INVOLVEMENT IN CDG1K; FUNCTION; VARIANTS CDG1K ARG-50; PHE-71; LEU-74; VAL-88; LEU-98; PHE-114; ARG-150; SER-209; LEU-258; TRP-276; PHE-281; GLY-289; VAL-291; ASP-353; ARG-358; LEU-359; VAL-360; ALA-363; GLN-366; GLN-367; LYS-382; ARG-384; SER-388 AND TRP-438; CHARACTERIZATION OF VARIANTS CDG1K ARG-50; PHE-71; LEU-74; VAL-88; LEU-98; PHE-114; ARG-150; SER-209; LEU-258; TRP-276; PHE-281; GLY-289; VAL-291; ASP-353; ARG-358; LEU-359; VAL-360; ALA-363; GLN-366; GLN-367; LYS-382; ARG-384; SER-388 AND TRP-438; CHARACTERIZATION OF VARIANT ASN-267;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9BT22: Variant p.Ser258Leu