Variant position:  244

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.]

Residue change:  From Isoleucine (I) to Threonine (T) at position 244 (I244T, p.Ile244Thr).

Physico-chemical properties:  Change from medium size and hydrophobic (I) to medium size and polar (T)

BLOSUM score:  -1

Variant description:  In HP1; prevalent mutation in the Canary islands; when associated with L-11 and M-340 on the minor AGXT allele; results in protein misfolding; decreased alanine--glyoxylate aminotransferase activity; no loss of dimerization; partial mitochondrial mistargeting.

Other resources:  

• Variant rs121908525 [ dbSNP | Ensembl ]

Variant position:  244

Protein sequence length:  392

Location on the sequence:   DKAKKKMYSRKTKPFSFYLD  I KWLANFWGCDDQPRMYHHTI

Residue conservation: 

Human                         DKAKKKMYSRKTKPFSFYLDIKWLANFWG-----CDDQ---------PRMYHHTI

Mouse                         DKAKYKVYSRKTKPVSFYTDITYLAKLWG-----CEGE---

Rat                           DKAKSKVYSRKTKPVSFYTDITYLSKLWG-----CEGK---

Rabbit                        DKAKSKIYARKTKPFSFYMDVQLLANIWG-----CDGK---

Cat                           DKAKNKIYTRKTKPVSFYLDMKWLANIWG-----CDGK---

Slime mold                    NAACHKIATRKTPVANWYLDCNLLGGYWCPEFNLADGTIAK

Sequence annotation in neighborhood:  

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;