UniProtKB/SwissProt variant VAR

Variant information

Variant position:

54

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 Cysteine (C) at position 54 (R54C, p.Arg54Cys).

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 medium size and polar (C)

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:

Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, 1 (CADASIL1) [MIM:125310]: A cerebrovascular disease characterized by multiple subcortical infarcts, pseudobulbar palsy, dementia, and the presence of granular deposits in small cerebral arteries producing ischemic stroke. {ECO:0000269|PubMed:10227618, ECO:0000269|PubMed:10371548, ECO:0000269|PubMed:10802807, ECO:0000269|PubMed:10854111, ECO:0000269|PubMed:11058919, ECO:0000269|PubMed:11102981, ECO:0000269|PubMed:11559313, ECO:0000269|PubMed:11755616, ECO:0000269|PubMed:11810186, ECO:0000269|PubMed:12136071, ECO:0000269|PubMed:12146805, ECO:0000269|PubMed:12589106, ECO:0000269|PubMed:12810003, ECO:0000269|PubMed:15229130, ECO:0000269|PubMed:15300988, ECO:0000269|PubMed:15350543, ECO:0000269|PubMed:15364702, ECO:0000269|PubMed:15378071, ECO:0000269|PubMed:15818833, ECO:0000269|PubMed:16009764, ECO:0000269|PubMed:24000151, ECO:0000269|PubMed:9388399}. 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 CADASIL1.

Any additional useful information about the variant.

Sequence information

Variant position:

54

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

Protein sequence length:

2321

The length of the canonical sequence.

Location on the sequence:

AGPGAAAPPCLDGSPCANGG R CTQLPSREAACLCPPGWVGE

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                         AGPGAAAPPCLDGSPCANGGRCT-QLPSREAACLCPPGWVGE

Mouse                         AGLGAAAPPCLDGSPCANGGRCTHQQPSLEAACLCLPGWVG

Rat                           AGLGAAAPPCLDGSPCANGGRCTHQQPSREAACLCLPGWVG

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	40 – 2321	Neurogenic locus notch homolog protein 3
Topological domain	40 – 1643	Extracellular
Domain	40 – 77	EGF-like 1
Disulfide bond	43 – 55
Disulfide bond	49 – 65

Literature citations

Diagnostic Notch3 sequence analysis in CADASIL: three new mutations in Dutch patients. Dutch CADASIL Research Group.
Lesnik Oberstein S.A.J.; Ferrari M.D.; Bakker E.; van Gestel J.; Kneppers A.L.J.; Frants R.R.; Breuning M.H.; Haan J.;
Neurology 52:1913-1915(1999)
Cited for: VARIANTS CADASIL1 CYS-133; CYS-141; CYS-153; CYS-182; CYS-207; CYS-544 AND ARG-1015;

Evaluation of DHPLC analysis in mutational scanning of Notch3, a gene with a high G-C content.
Escary J.-L.; Cecillon M.; Maciazek J.; Lathrop M.; Tournier-Lasserve E.; Joutel A.;
Hum. Mutat. 16:518-526(2000)
Cited for: VARIANTS CADASIL1 TYR-49; CYS-54; CYS-90; CYS-110; 114-GLY--PRO-120 DEL; TYR-123; CYS-133; CYS-141; ARG-146; CYS-153; SER-162; CYS-169; TYR-174; CYS-180; CYS-182; ARG-185; TYR-194; TYR-206; CYS-207; SER-212; GLY-222; TYR-224; CYS-258; TYR-542; CYS-558; CYS-578; CYS-607; CYS-728; CYS-984; CYS-985; CYS-1006; CYS-1031; CYS-1231 AND ARG-1261;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9UM47: Variant p.Arg54Cys