UniProtKB/Swiss-Prot P30566: Variant p.Asp268Asn

Adenylosuccinate lyase
Gene: ADSL
Chromosomal location: 22q13.2
Variant information

Variant position:  268
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 Aspartate (D) to Asparagine (N) at position 268 (D268N, p.Asp268Asn).
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 medium size and acidic (D) to medium size and polar (N)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
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 (ADSL deficiency) [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. 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 ADSL deficiency; severe. Total loss of activity.
Any additional useful information about the variant.



Sequence information

Variant position:  268
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:   DIEVLSVLASLGASVHKICT  D IRLLANLKEMEEPFEKQQIG
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                         DIEVLSVLASLGASVHKICTDIRLLANLKEMEEPFEKQQIG

Mouse                         DIEVLSVLASLGASVHKICTDIRLLANLKEMEEPFEKQQIG

Bovine                        DIEVLSVLASLGASVHKICTDIRLLANLKEMEEPFEKQQIG

Chicken                       DIEVLSVLASLGASVHKICTDIRLLANLKEIEEPFEKDQIG

Caenorhabditis elegans        DSQLVFSLSLLGAAAKKVCTDIRVLQAFGELLEPFEKDQIG

Slime mold                    VASLLDAFKRINTILIDLCRDIWTYISMEYFNQKLVKGEVG

Baker's yeast                 DIDVLAPLSSFAATAHKMATDIRLLANLKEVEEPFEKSQIG

Fission yeast                 DIDVLQPLASFGATAHKIATDIRLLANLKEVEEPFEAGQIG

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
Helix 246 – 274


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;

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.