UniProtKB/Swiss-Prot P30566: Variant p.Arg194Cys

Adenylosuccinate lyase
Gene: ADSL
Chromosomal location: 22q13.2
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

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

Variant description:  In ADSL deficiency; severe. Reduces protein stability.
Any additional useful information about the variant.



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.

TypePositionsDescription
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); VARIANTS ADSL DEFICIENCY 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 ADSL DEFICIENCY CYS-194; GLU-246; VAL-311; CYS-396 AND HIS-396; ENZYME REGULATION;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.