UniProtKB/SwissProt variant VAR

Variant information

Variant position:

565

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 565 (R565W, p.Arg565Trp).

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

Involvement in disease:

Polymicrogyria, bilateral frontoparietal (BFPP) [MIM:606854]: A malformation of the cortex in which the brain surface is irregular and characterized by an excessive number of small gyri with abnormal lamination, most severe in the frontoparietal regions. BFPP clinical manifestations include developmental and psychomotor delay, cerebellar and pyramidal signs, truncal ataxia, seizures, hyperreflexia. Polymicrogyria is a heterogeneous disorder, considered to be the result of postmigratory abnormal cortical organization. {ECO:0000269|PubMed:15044805, ECO:0000269|PubMed:16240336, ECO:0000269|PubMed:21349848, ECO:0000269|PubMed:21723461, ECO:0000269|PubMed:22238662, ECO:0000269|PubMed:24949629}. 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 BFPP; reduces cell surface localization.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121908464 [ dbSNP | Ensembl ]

Sequence information

Variant position:

565

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

Protein sequence length:

693

The length of the canonical sequence.

Location on the sequence:

IILAVHRTPEGVIYPSMCWI R DSLVSYITNLGLFSLVFLFN

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                         IILAVHRTPEGVIYPSMCWIRDSLVSYITNLGLFSLVFLFN

Gorilla                       IILAVHRTPEGVIYPSMCWIRDSLVSYITNLGLFSLVFLFN

Rhesus macaque                IILAVHRTPESVIYPSMCWIRDSLVSYITNLGLFSLVFLFN

Chimpanzee                    IILAVHRTPEGVIYPSMCWIRDSLVSYITNLGLFSLVFLFN

Mouse                         IILAVRRTPERVTYPSMCWIRDSLVSYVTNLGLFSLVFLFN

Rat                           IILAVRRTPDHVIYPSMCWIRDSVVSYVTNLGLFSLVFLFN

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	26 – 693	Adhesion G-protein coupled receptor G1
Chain	383 – 693	ADGRG1 C-terminal fragment
Topological domain	540 – 576	Extracellular

Literature citations

Disease-associated GPR56 mutations cause bilateral frontoparietal polymicrogyria via multiple mechanisms.
Chiang N.Y.; Hsiao C.C.; Huang Y.S.; Chen H.Y.; Hsieh I.J.; Chang G.W.; Lin H.H.;
J. Biol. Chem. 286:14215-14225(2011)
Cited for: SUBUNIT; SUBCELLULAR LOCATION (ADGRG1 N-TERMINAL FRAGMENT); GLYCOSYLATION; CHARACTERIZATION OF VARIANTS BFPP TRP-38; CYS-88; SER-91; SER-346; SER-349; TRP-565 AND ARG-640; MUTAGENESIS OF THR-383;

G protein-coupled receptor-dependent development of human frontal cortex.
Piao X.; Hill R.S.; Bodell A.; Chang B.S.; Basel-Vanagaite L.; Straussberg R.; Dobyns W.B.; Qasrawi B.; Winter R.M.; Innes A.M.; Voit T.; Ross M.E.; Michaud J.L.; Descarie J.-C.; Barkovich A.J.; Walsh C.A.;
Science 303:2033-2036(2004)
Cited for: VARIANTS BFPP TRP-38; CYS-88; SER-91; SER-346 AND TRP-565;

Genotype-phenotype analysis of human frontoparietal polymicrogyria syndromes.
Piao X.; Chang B.S.; Bodell A.; Woods K.; Benzeev B.; Topcu M.; Guerrini R.; Goldberg-Stern H.; Sztriha L.; Dobyns W.B.; Barkovich A.J.; Walsh C.A.;
Ann. Neurol. 58:680-687(2005)
Cited for: VARIANTS BFPP GLN-38; TRP-38; SER-349; TRP-565 AND ARG-640;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9Y653: Variant p.Arg565Trp