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UniProtKB/Swiss-Prot P00966: Variant p.Ala118Thr

Argininosuccinate synthase
Gene: ASS1
Variant information

Variant position:  118
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Alanine (A) to Threonine (T) at position 118 (A118T, p.Ala118Thr).
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 small size and hydrophobic (A) to medium size and polar (T)
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

Variant description:  In CTLN1; decreased thermal stability; decreased affinity for aspartate; decreased affinity for citrulline; decreased argininosuccinate synthase activity.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  118
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  412
The length of the canonical sequence.

Location on the sequence:   IARKQVEIAQREGAKYVSHG  A TGKGNDQVRFELSCYSLAPQ
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                         IARKQVEIAQREGAKYVSHGATGKGNDQVRFELSCYSLAPQ

Mouse                         IARRQVEIAQREGAKYVSHGATGKGNDQVRFELTCYSLAPQ

Rat                           IARKQVEIAQREGAKYVSHGATGKGNDQVRFELTCYSLAPQ

Bovine                        IARKQVEIAQREGAKYVSHGATGKGNDQIRFELTCYSLAPQ

Chicken                       IARHLVLIAQEEGARYIAHGATGKGNDQVRFELGCYALCPS

Xenopus laevis                IAKKQVEIAKKEAAEYVSHGATGKGNDQIRFELTCYSLYPE

Xenopus tropicalis            IAKKQVEIAKKEAAEYVSHGATGKGNDQIRFELTCYALYPE

Zebrafish                     IARRQVQIAQREGAQYVSHGATGKGNDQVRFELTCYALYPQ

Drosophila                    ISVALMEVAREYGAKYLAHGATGKGNDQVRFELCAYALKPD

Baker's yeast                 IAKAQIDVAKQEGCFAVSHGCTGKGNDQIRFELSFYALKPD

Fission yeast                 IARRQIQIAEKENCIAVSHGCTGKGNDQVRFELAYYALKPD

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 1 – 412 Argininosuccinate synthase
Nucleotide binding 115 – 123 ATP
Binding site 119 – 119 Aspartate
Binding site 123 – 123 Aspartate
Binding site 123 – 123 Citrulline
Binding site 124 – 124 Aspartate
Binding site 127 – 127 Citrulline
Modified residue 112 – 112 N6-acetyllysine
Modified residue 113 – 113 Phosphotyrosine


Literature citations

Mutations in argininosuccinate synthetase mRNA of Japanese patients, causing classical citrullinemia.
Kobayashi K.; Shaheen N.; Terazono H.; Saheki T.;
Am. J. Hum. Genet. 55:1103-1112(1994)
Cited for: VARIANTS CTLN1 THR-118; VAL-192; CYS-272; ARG-280; TRP-304 AND LEU-363;

Investigation of citrullinemia type I variants by in vitro expression studies.
Berning C.; Bieger I.; Pauli S.; Vermeulen T.; Vogl T.; Rummel T.; Hoehne W.; Koch H.G.; Rolinski B.; Gempel K.; Haeberle J.;
Hum. Mutat. 29:1222-1227(2008)
Cited for: VARIANTS CTLN1 CYS-265 AND VAL-302; CHARACTERIZATION OF VARIANTS CTLN1 THR-118; ARG-179; VAL-263; CYS-265; VAL-302; SER-324; VAL-362 AND ARG-390; FUNCTION; CATALYTIC ACTIVITY; PATHWAY; BIOPHYSICOCHEMICAL PROPERTIES;

Kinetic mutations in argininosuccinate synthetase deficiency: characterisation and in vitro correction by substrate supplementation.
Diez-Fernandez C.; Wellauer O.; Gemperle C.; Ruefenacht V.; Fingerhut R.; Haeberle J.;
J. Med. Genet. 53:710-719(2016)
Cited for: VARIANTS CTLN1 PRO-91; LEU-96; SER-117; THR-118; ILE-119; ASN-124; CYS-157; HIS-157; CYS-272; HIS-272 AND LEU-272; CHARACTERIZATION OF VARIANTS CTLN1 PRO-91; SER-95; HIS-96; LEU-96; SER-96; SER-117; THR-118; ILE-119; ASN-124; GLN-127; TRP-127; CYS-157; HIS-157; ASN-180; ILE-180; GLN-191; GLN-270; CYS-272; HIS-272 AND LEU-272; CHARACTERIZATION OF VARIANT LEU-127; CATALYTIC ACTIVITY; PATHWAY; FUNCTION; SUBCELLULAR LOCATION;

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.