UniProtKB/Swiss-Prot P30566: Variant p.Arg396His

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

Variant position:  396
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 Histidine (H) at position 396 (R396H, p.Arg396His).
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 (H)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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. Abolishes cooperativity and reduces enzyme activity.
Any additional useful information about the variant.



Sequence information

Variant position:  396
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:   ELPFMATENIIMAMVKAGGS  R QDCHEKIRVLSQQAASVVKQ
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                         ELPFMATENIIMAMVKAGGSRQDCHEKIRVLSQQAASVVKQ

Mouse                         ELPFMATENIIMAMVKAGGSRQDCHEKIRVLSQQAAAVVKQ

Bovine                        ELPFMATENIIMAMVKAGGNRQDCREKIRVLSQQAAAVVKQ

Chicken                       ELPFMATENIIMAMVKAGGNRQDCHEKIRVLSQQAAAVVKQ

Caenorhabditis elegans        EIAFLGLEKAMMMLTEEGVDRQQAHAVIRKTALEAKQLQAT

Slime mold                    NWAVV-SEAIQTILRREGFPKP--YEALKELTRVSGSKKIT

Baker's yeast                 ELPFMATENIIMAMVEKNASRQEVHERIRVLSHQAAAVVKE

Fission yeast                 ELPFMATENIIMAMTKHGASRHECHEQIRVLSHQAGRVVKE

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 396 – 416


Literature citations

Screening for adenylosuccinate lyase deficiency: clinical, biochemical and molecular findings in four patients.
Castro M.; Perez-Cerda C.; Merinero B.; Garcia M.J.; Bernar J.; Gil Nagel A.; Torres J.; Bermudez M.; Garavito P.; Marie S.; Vincent F.; Van den Berghe G.; Ugarte M.;
Neuropediatrics 33:186-189(2002)
Cited for: VARIANTS ADSL DEFICIENCY VAL-311; MET-364; HIS-396 AND PRO-452;

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.