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UniProtKB/Swiss-Prot P21549: Variant p.Phe152Ile

Serine--pyruvate aminotransferase
Gene: AGXT
Chromosomal location: 2q37.3
Variant information

Variant position:  152
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Phenylalanine (F) to Isoleucine (I) at position 152 (F152I, p.Phe152Ile).
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 aromatic (F) to medium size and hydrophobic (I)
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:  Hyperoxaluria primary 1 (HP1) [MIM:259900]: An inborn error of glyoxylate metabolism characterized by increased excretion of oxalate and glycolate, and progressive tissue accumulation of insoluble calcium oxalate. Affected individuals are at risk for nephrolithiasis, nephrocalcinosis and early onset end-stage renal disease. {ECO:0000269|PubMed:10394939, ECO:0000269|PubMed:10453743, ECO:0000269|PubMed:10541294, ECO:0000269|PubMed:10862087, ECO:0000269|PubMed:10960483, ECO:0000269|PubMed:12559847, ECO:0000269|PubMed:12777626, ECO:0000269|PubMed:1301173, ECO:0000269|PubMed:1349575, ECO:0000269|PubMed:15253729, ECO:0000269|PubMed:15849466, ECO:0000269|PubMed:15961946, ECO:0000269|PubMed:15963748, ECO:0000269|PubMed:16971151, ECO:0000269|PubMed:1703535, ECO:0000269|PubMed:17495019, ECO:0000269|PubMed:2039493, ECO:0000269|PubMed:23229545, ECO:0000269|PubMed:24055001, ECO:0000269|PubMed:24934730, ECO:0000269|PubMed:26149463, ECO:0000269|PubMed:8101040, ECO:0000269|PubMed:9192270, ECO:0000269|PubMed:9604803}. 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 HP1; when associated with L-11 and M-340 on the minor AGXT allele; results in protein destabilization; decreased alanine--glyoxylate aminotransferase activity; no loss of dimerization; mitochondrial mistargeting.
Any additional useful information about the variant.

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



Sequence information

Variant position:  152
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:   GHYTLQEVEEGLAQHKPVLL  F LTHGESSTGVLQPLDGFGEL
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                         GHYTLQEVEEGLAQHKPVLLFLTHGESSTGVLQPLDGFGEL

Mouse                         EHYTLQEVEEGLAQHKPVLLFLVHGESSTGVVQPLDGFGEL

Rat                           EHYTLQEVEEGLAQHKPVLLFLTHGESSTGVLQPLDGFGEL

Rabbit                        SHYTLQEVEECLAQHKPVLLFLTHGESSTGVLQPLDGFGEL

Cat                           NHYTLQELEEALAQHKPVLLFLTQGESSSGVLQPLDGYGEL

Slime mold                    QWFALEEIESALVQHKPSLLTLVFGETSTGVKQQMEGVGEL

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 – 392 Serine--pyruvate aminotransferase
Beta strand 149 – 156


Literature citations

Enzymological and mutational analysis of a complex primary hyperoxaluria type 1 phenotype involving alanine:glyoxylate aminotransferase peroxisome-to-mitochondrion mistargeting and intraperoxisomal aggregation.
Danpure C.J.; Purdue P.E.; Fryer P.; Griffiths S.; Allsop J.; Lumb M.J.; Guttridge K.M.; Jennings P.R.; Scheinman J.I.; Mauer S.M.; Davidson N.O.;
Am. J. Hum. Genet. 53:417-432(1993)
Cited for: VARIANTS HP1 ARG-41 AND ILE-152;

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;

Clinical implications of mutation analysis in primary hyperoxaluria type 1.
van Woerden C.S.; Groothoff J.W.; Wijburg F.A.; Annink C.; Wanders R.J.A.; Waterham H.R.;
Kidney Int. 66:746-752(2004)
Cited for: VARIANTS HP1 ARG-82; ILE-152; VAL-153; ARG-170 AND ASP-336;

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; SUBCELLULAR LOCATION; SUBUNIT;

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.