UniProtKB/SwissProt variant VAR

Variant information

Variant position:

171

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 Serine (S) to Phenylalanine (F) at position 171 (S171F, p.Ser171Phe).

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 large size and aromatic (F)

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:

Leukodystrophy with vanishing white matter (VWM) [MIM:603896]: A leukodystrophy that occurs mainly in children. Neurological signs include progressive cerebellar ataxia, spasticity, inconstant optic atrophy and relatively preserved mental abilities. The disease is chronic-progressive with, in most individuals, additional episodes of rapid deterioration following febrile infections or minor head trauma. While childhood onset is the most common form of the disorder, some severe forms are apparent at birth. A severe, early-onset form seen among the Cree and Chippewayan populations of Quebec and Manitoba is called Cree leukoencephalopathy. Milder forms may not become evident until adolescence or adulthood. Some females with milder forms of the disease who survive to adolescence exhibit ovarian dysfunction. This variant of the disorder is called ovarioleukodystrophy. {ECO:0000269|PubMed:11704758, ECO:0000269|PubMed:12707859, ECO:0000269|PubMed:15776425, ECO:0000269|PubMed:21484434, ECO:0000269|PubMed:22285377, ECO:0000269|PubMed:22729508}. 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 VWM; with ovarian failure.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104894428 [ dbSNP | Ensembl ]

Sequence information

Variant position:

171

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

Protein sequence length:

351

The length of the canonical sequence.

Location on the sequence:

IAAQALEHIHSNEVIMTIGF S RTVEAFLKEAARKRKFHVIV

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                         IAAQALEHIHSNEVIMTIGF-SRTVEAFLKEAARK--RKFHVIV

Mouse                         IAAQALEHIHSNEVIMTIGY-SRTVEAFLKEAARK--RKFH

Rat                           IAAQALEHIHSNEVIMTIGF-SRTVEAFLREAAQK--RKFH

Bovine                        IAAQALEHIHSNEVIMTIGF-SRTVEAFLREAARK--RKFH

Rabbit                        IAAQALEHIHSNEVIMTIGL-SRTVEAFLREAARK--RKFH

Slime mold                    VAEQAIEHIHSNETIMTLGC-SRTVEEFLKEAARK--RSFK

Baker's yeast                 IQQIAIDLIHDHEILLTPTPDSKTVLKFLITARERSNRTFT

Fission yeast                 IEVQSMDHLHSNEIILTQGC-SKTVEAFLRFAAKK--RKFS

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 – 351	Translation initiation factor eIF-2B subunit beta

Literature citations

Ovarian failure related to eukaryotic initiation factor 2B mutations.
Fogli A.; Rodriguez D.; Eymard-Pierre E.; Bouhour F.; Labauge P.; Meaney B.F.; Zeesman S.; Kaneski C.R.; Schiffmann R.; Boespflug-Tanguy O.;
Am. J. Hum. Genet. 72:1544-1550(2003)
Cited for: VARIANTS VWM PHE-171 AND GLY-213;

Identification of ten novel mutations in patients with eIF2B-related disorders.
Ohlenbusch A.; Henneke M.; Brockmann K.; Goerg M.; Hanefeld F.; Kohlschutter A.; Gartner J.;
Hum. Mutat. 25:411-411(2005)
Cited for: VARIANTS VWM PHE-171; SER-196; VAL-200 AND GLY-213;

UniProtKB/Swiss-Prot P49770: Variant p.Ser171Phe