UniProtKB/Swiss-Prot P21549: Variant p.Ile244Thr

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 244 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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 Isoleucine (I) to Threonine (T) at position 244 (I244T, p.Ile244Thr). 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 hydrophobic (I) to medium size and polar (T) 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
Variant description: In HP1; associated in cis with L-11 and M-340; results in protein misfolding; decreased alanine--glyoxylate aminotransferase activity in vitro; no loss of dimerization; partial mitochondrial mistargeting; loss of alanine--glyoxylate aminotransferase activity in vitro when associated with L-11 and M-340. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs121908525 [ dbSNP | Ensembl ]

Sequence information

Variant position: 244 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 392 The length of the canonical sequence.
Location on the sequence: DKAKKKMYSRKTKPFSFYLD I KWLANFWGCDDQPRMYHHTI 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.
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	1 – 392	Alanine--glyoxylate aminotransferase
Modified residue	225 – 225	N6-acetyllysine; alternate
Modified residue	225 – 225	N6-succinyllysine; alternate
Modified residue	234 – 234	N6-acetyllysine
Helix	244 – 250

Literature citations

Primary hyperoxaluria type 1: a cluster of new mutations in exon 7 of the AGXT gene.
von Schnakenburg C.; Rumsby G.;
J. Med. Genet. 34:489-492(1997)
Cited for: VARIANTS HP1 CYS-233; HIS-233 AND THR-244; Primary hyperoxaluria type I: a model for multiple mutations in a monogenic disease within a distinct ethnic group.
Rinat C.; Wanders R.J.A.; Drukker A.; Halle D.; Frishberg Y.;
J. Am. Soc. Nephrol. 10:2352-2358(1999)
Cited for: VARIANTS HP1 ARG-41; ARG-156; ARG-190; THR-244; CYS-289 AND PRO-298; Identification of 5 novel mutations in the AGXT gene.
Basmaison O.; Rolland M.-O.; Cochat P.; Bozon D.;
Hum. Mutat. 15:577-577(2000)
Cited for: VARIANTS HP1 ILE-152; ARG-170; ASN-183; CYS-233 AND THR-244; Functional synergism between the most common polymorphism in human alanine:glyoxylate aminotransferase and four of the most common disease-causing mutations.
Lumb M.J.; Danpure C.J.;
J. Biol. Chem. 275:36415-36422(2000)
Cited for: CHARACTERIZATION OF VARIANTS HP1 ARG-41; GLU-82; ILE-152; ARG-170 AND THR-244; CHARACTERIZATION OF VARIANT LEU-11; MUTAGENESIS OF LYS-209; FUNCTION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION; COFACTOR; SUBUNIT; BIOPHYSICOCHEMICAL PROPERTIES; ACTIVITY REGULATION; Primary hyperoxaluria type 1 in the Canary Islands: a conformational disease due to I244T mutation in the P11L-containing alanine:glyoxylate aminotransferase.
Santana A.; Salido E.; Torres A.; Shapiro L.J.;
Proc. Natl. Acad. Sci. U.S.A. 100:7277-7282(2003)
Cited for: CHARACTERIZATION OF VARIANT HP1 THR-244; FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; SUBUNIT; SUBCELLULAR LOCATION; Implications of genotype and enzyme phenotype in pyridoxine response of patients with type I primary hyperoxaluria.
Monico C.G.; Olson J.B.; Milliner D.S.;
Am. J. Nephrol. 25:183-188(2005)
Cited for: VARIANTS HP1 VAL-139 DEL; ARG-156; LEU-158; ARG-190; GLU-201; LEU-233; THR-244 AND ARG-253; VARIANT ASN-9; Intra-familial clinical heterogeneity: absence of genotype-phenotype correlation in primary hyperoxaluria type 1 in Israel.
Frishberg Y.; Rinat C.; Shalata A.; Khatib I.; Feinstein S.; Becker-Cohen R.; Weismann I.; Wanders R.J.A.; Rumsby G.; Roels F.; Mandel H.;
Am. J. Nephrol. 25:269-275(2005)
Cited for: VARIANTS HP1 ARG-41; ARG-108; ARG-156; ARG-190; ARG-195; HIS-243; THR-244; MET-279; THR-287; CYS-289 AND PRO-298; VARIANT ASN-9; Selected exonic sequencing of the AGXT gene provides a genetic diagnosis in 50% of patients with primary hyperoxaluria type 1.
Williams E.; Rumsby G.;
Clin. Chem. 53:1216-1221(2007)
Cited for: VARIANTS HP1 CYS-36; ARG-41; GLU-41; PRO-150; ILE-152; ARG-156; LEU-158; CYS-161; SER-161; PRO-166; ARG-170; TYR-173; CYS-233; HIS-233; THR-244 AND ARG-253; VARIANT ASN-9; CHARACTERIZATION OF VARIANTS HP1 CYS-36; GLU-41; PRO-150; ARG-156; LEU-158; CYS-161; SER-161; PRO-166; TYR-173; CYS-233; HIS-233 AND ARG-253; CHARACTERIZATION OF VARIANT ASN-9; Four of the most common mutations in primary hyperoxaluria type 1 unmask the cryptic mitochondrial targeting sequence of alanine:glyoxylate aminotransferase encoded by the polymorphic minor allele.
Fargue S.; Lewin J.; Rumsby G.; Danpure C.J.;
J. Biol. Chem. 288:2475-2484(2013)
Cited for: CHARACTERIZATION OF VARIANTS HP1 ARG-41; ILE-152; ARG-170 AND THR-244; FUNCTION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION; SUBUNIT;