UniProtKB/SwissProt variant VAR

Variant information

Variant position:

194

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 194 (R194C, p.Arg194Cys).

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:

Adenylosuccinase deficiency (ADSLD) [MIM:103050]: An autosomal recessive disorder characterized by the accumulation in the body fluids of succinylaminoimidazole-carboxamide riboside (SAICA-riboside) and succinyladenosine (S-Ado). Most children display marked psychomotor delay, often accompanied by epilepsy or autistic features, or both, although some patients may be less profoundly retarded. Occasionally, growth retardation and muscular wasting are also present. {ECO:0000269|PubMed:10090474, ECO:0000269|PubMed:10888601, ECO:0000269|PubMed:10958654, ECO:0000269|PubMed:12368987, ECO:0000269|PubMed:12833398, ECO:0000269|PubMed:1302001, ECO:0000269|PubMed:19405474, ECO:0000269|PubMed:22812634, ECO:0000269|PubMed:9266401, ECO:0000269|PubMed:9545543}. 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 ADSLD; severe; reduces protein stability.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs1465152683 [ dbSNP | Ensembl ]

Sequence information

Variant position:

194

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

Protein sequence length:

484

The length of the canonical sequence.

Location on the sequence:

LWIQDLCMDLQNLKRVRDDL R FRGVKGTTGTQASFLQLFEG

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                         LWIQDLCMDLQNLKR-VRDDLRFRGVKGT-TGTQASFLQLFEG

Mouse                         LWIQDLCMDLQNLKR-VRDELRFRGVKGT-TGTQASFLQLF

Bovine                        LWIQDLCMDLQNLKR-VRDELRFRGVKGT-TGTQASFLQLF

Chicken                       LWIQDLCMDLQNLER-ARDDLRFRGVKGT-TGTQASFLQLF

Caenorhabditis elegans        LWAQELLMAFQSLSE-FRDKMRFRGIKGA-TGTQDSFLTLF

Slime mold                    VFIERLENQINHLEQSVPHTCKFGGATGNLNAHKVSYPAI-

Baker's yeast                 LWIQELLWDLRNFER-ARNDIGLRGVKGT-TGTQASFLALF

Fission yeast                 LWIQELLWDLRNFVR-ARNDIGFRGVKGT-TGTQASFLALF

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	2 – 484	Adenylosuccinate lyase

Literature citations

Human adenylosuccinate lyase (ADSL), cloning and characterization of full-length cDNA and its isoform, gene structure and molecular basis for ADSL deficiency in six patients.
Kmoch S.; Hartmannova H.; Stiburkova B.; Krijt J.; Zikanova M.; Sebesta I.;
Hum. Mol. Genet. 9:1501-1513(2000)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2); FUNCTION; VARIANTS ADSLD VAL-3; HIS-114; GLN-190; CYS-194; ASN-268; HIS-426 AND ASN-430;

Biochemical and biophysical analysis of five disease-associated human adenylosuccinate lyase mutants.
Ariyananda Lde Z.; Lee P.; Antonopoulos C.; Colman R.F.;
Biochemistry 48:5291-5302(2009)
Cited for: CHARACTERIZATION OF VARIANTS ADSLD CYS-194; GLU-246; VAL-311; CYS-396 AND HIS-396; ACTIVITY REGULATION;

UniProtKB/Swiss-Prot P30566: Variant p.Arg194Cys