UniProtKB/SwissProt variant VAR

Variant information

Variant position:

416

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 Arginine (R) to Tryptophan (W) at position 416 (R416W, p.Arg416Trp).

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 (R) to large size and aromatic (W)

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

BLOSUM score:

-3

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 ALXDRD.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121909717 [ dbSNP | Ensembl ]

Sequence information

Variant position:

416

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

Protein sequence length:

432

The length of the canonical sequence.

Location on the sequence:

TKSVSEGHLKRNIVVKTVEM R DGEVIKESKQEHKDVM

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                         TKSVSEGHLKRNIVVKTVEMRDGEVIKESKQEHKDVM-

Mouse                         TKSVSEGHLKRNIVVKTVEMRDGEVIKDSKQEHKDVV

Rat                           TKSVSEGHLKRNIVVKTVEMRDGEVIKESKQEHKDVM

Bovine                        TKSVSEGHLKRNIVVKTVEMRDGEVIKESKQEHKDVM

Zebrafish                     TKLTPEAHVKRSIVVRTVETRDGEIIKESTTERKDLP

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 – 432	Glial fibrillary acidic protein
Region	378 – 432	Tail
Modified residue	406 – 406	Citrulline
Modified residue	416 – 416	Citrulline
Alternative sequence	391 – 432	ETSLDTKSVSEGHLKRNIVVKTVEMRDGEVIKESKQEHKDVM -> GQYSRASWEGHWSPAPSSRACRLLQTGTEDQGKGIQLSLGAFVTLQRS. In isoform 2.
Alternative sequence	391 – 432	ETSLDTKSVSEGHLKRNIVVKTVEMRDGEVIKESKQEHKDVM -> GGKSTKDGENHKVTRYLKSLTIRVIPIQAHQIVNGTPPARG. In isoform 3.

Literature citations

Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease.
Brenner M.; Johnson A.B.; Boespflug-Tanguy O.; Rodriguez D.; Goldman J.E.; Messing A.;
Nat. Genet. 27:117-120(2001)
Cited for: INVOLVEMENT IN ALXDRD; VARIANTS ALXDRD CYS-79; HIS-79; CYS-239; HIS-239; PRO-258 AND TRP-416; VARIANTS LEU-47 AND ASN-295;

Molecular findings in symptomatic and pre-symptomatic Alexander disease patients.
Gorospe J.R.; Naidu S.; Johnson A.B.; Puri V.; Raymond G.V.; Jenkins S.D.; Pedersen R.C.; Lewis D.; Knowles P.; Fernandez R.; De Vivo D.; van der Knaap M.S.; Messing A.; Brenner M.; Hoffman E.P.;
Neurology 58:1494-1500(2002)
Cited for: VARIANTS ALXDRD ARG-73; GLY-79; CYS-79; HIS-79; CYS-88; CYS-239; ASP-242; LYS-373 AND TRP-416;

Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease.
Li R.; Johnson A.B.; Salomons G.; Goldman J.E.; Naidu S.; Quinlan R.; Cree B.; Ruyle S.Z.; Banwell B.; D'Hooghe M.; Siebert J.R.; Rolf C.M.; Cox H.; Reddy A.; Gutierrez-Solana L.G.; Collins A.; Weller R.O.; Messing A.; van der Knaap M.S.; Brenner M.;
Ann. Neurol. 57:310-326(2005)
Cited for: VARIANTS LEU-47; ILE-115; ASN-157 AND GLN-223; VARIANTS ALXDRD GLN-63; THR-73; PHE-76; VAL-76; SER-77; CYS-79; CYS-88; PRO-97; LYS-207; GLN-207; LYS-210; PRO-235; CYS-239; HIS-239; PRO-239; VAL-244; GLY-253; GLU-279; PRO-352; VAL-359; PRO-364; HIS-366; LYS-373; GLN-373; GLY-374 AND TRP-416; CHARACTERIZATION OF VARIANTS ALXDRD GLN-63; LYS-210; VAL-244 AND GLY-253; CHARACTERIZATION OF VARIANT ILE-115;

GFAP mutations and polymorphisms in 13 unrelated Italian patients affected by Alexander disease.
Caroli F.; Biancheri R.; Seri M.; Rossi A.; Pessagno A.; Bugiani M.; Corsolini F.; Savasta S.; Romano S.; Antonelli C.; Romano A.; Pareyson D.; Gambero P.; Uziel G.; Ravazzolo R.; Ceccherini I.; Filocamo M.;
Clin. Genet. 72:427-433(2007)
Cited for: VARIANTS ALXDRD TRP-70; GLN-70; LYS-73; SER-77; CYS-79; PRO-79; CYS-88; HIS-239; PRO-239; PRO-359 AND TRP-416;

Diagnosis by whole exome sequencing of atypical infantile onset Alexander disease masquerading as a mitochondrial disorder.
Nishri D.; Edvardson S.; Lev D.; Leshinsky-Silver E.; Ben-Sira L.; Henneke M.; Lerman-Sagie T.; Blumkin L.;
Eur. J. Paediatr. Neurol. 18:495-501(2014)
Cited for: VARIANT ALXDRD TRP-416;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P14136: Variant p.Arg416Trp