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UniProtKB/Swiss-Prot P37231: Variant p.Pro12Ala

Peroxisome proliferator-activated receptor gamma
Gene: PPARG
Variant information

Variant position:  12
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 Proline (P) to Alanine (A) at position 12 (P12A, p.Pro12Ala).
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 (P) to small size and hydrophobic (A)
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

Polymorphism:  Genetic variations in PPARG define the body mass index quantitative trait locus 1 (BMIQ1) [MIM:606641]. The body max index (BMI) reflects the amount of fat, lean mass, and body build.Genetic variations in PPARG influence the carotid intimal medial thickness (CIMT) [MIM:609338]. CIMT is a measure of atherosclerosis that is independently associated with traditional atherosclerotic cardiovascular disease risk factors and coronary atherosclerotic burden. 35 to 45% of the variability in multivariable-adjusted CIMT is explained by genetic factors. -
Additional information on the polymorphism described.

Variant description:  Polymorphism; significant independent determinant of CIMT; may protect from early atherosclerosis in subject at risk for diabetes; associated with BMI.
Any additional useful information about the variant.

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



Sequence information

Variant position:  12
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  505
The length of the canonical sequence.

Location on the sequence:   MGETLGDSPID  P ESDSFTDTLSANISQEMTMV
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                         MGETLGDSPIDPESDSFTDTLSANISQEMTMV

                              MGETLGDSLIDPESDSFADTLSASTSQETTMV

Rhesus macaque                MGETLGDSPIDPESDSFTDTLSANISQEITMV

Mouse                         MGETLGDSPVDPEHGAFADALPMSTSQEITMV

Rat                           MGETLGDPPVDPEHGAFADALPMSTSQEITMV

Pig                           MGETLGDSLIDPESDAF-DTLSANISQEVTMV

Bovine                        MGETLGDALIDPESEPFAVTVSARTSQEITMV

Rabbit                        ------------------------------MV

Xenopus laevis                ------------------------------MV

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 – 505 Peroxisome proliferator-activated receptor gamma
Alternative sequence 1 – 28 Missing. In isoform 1 and isoform 3.


Literature citations

Submission
SeattleSNPs variation discovery resource;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANT ALA-12;

Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR-gamma) gene in diabetic Caucasians: identification of a pro12ala PPAR-gamma-2 missense mutation.
Yen C.-J.; Beamer B.A.; Negri C.; Silver K.; Brown K.A.; Yarnall D.P.; Burns D.K.; Roth J.; Shuldiner A.R.;
Biochem. Biophys. Res. Commun. 241:270-274(1997)
Cited for: VARIANT ALA-12;

A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity.
Deeb S.S.; Fajas L.; Nemoto M.; Pihlajamaeki J.; Mykkaenen L.; Kuusisto J.; Laakso M.; Fujimoto W.; Auwerx J.;
Nat. Genet. 20:284-287(1998)
Cited for: INVOLVEMENT IN BMIQ1; VARIANT ALA-12;

Missense variants in the human peroxisome proliferator-activated receptor-gamma2 gene in lean and obese subjects.
Hamann A.; Munzberg H.; Buttron P.; Busing B.; Hinney A.; Mayer H.; Siegfried W.; Hebebrand J.; Greten H.;
Eur. J. Endocrinol. 141:90-92(1999)
Cited for: VARIANT ALA-12;

Two polymorphisms in the peroxisome proliferator-activated receptor-gamma gene are associated with severe overweight among obese women.
Valve R.; Sivenius K.; Miettinen R.; Pihlajamaeki J.; Rissanen A.; Deeb S.S.; Auwerx J.; Uusitupa M.; Laakso M.;
J. Clin. Endocrinol. Metab. 84:3708-3712(1999)
Cited for: INVOLVEMENT IN BMIQ1; VARIANT ALA-12;

Loss-of-function mutations in PPAR-gamma associated with human colon cancer.
Sarraf P.; Mueller E.; Smith W.M.; Wright H.M.; Kum J.B.; Aaltonen L.A.; de la Chapelle A.; Spiegelman B.M.; Eng C.;
Mol. Cell 3:799-804(1999)
Cited for: VARIANTS COLON CANCER PRO-314 AND HIS-316; VARIANT ALA-12;

Effect of the peroxisome proliferator activated receptor-gamma gene Pro12Ala variant on body mass index: a meta-analysis.
Masud S.; Ye S.;
J. Med. Genet. 40:773-780(2003)
Cited for: ASSOCIATION OF VARIANT ALA-12 WITH BMI;

Ala12Ala genotype of the peroxisome proliferator-activated receptor gamma2 protects against atherosclerosis.
Temelkova-Kurktschiev T.; Hanefeld M.; Chinetti G.; Zawadzki C.; Haulon S.; Kubaszek A.; Koehler C.; Leonhardt W.; Staels B.; Laakso M.;
J. Clin. Endocrinol. Metab. 89:4238-4242(2004)
Cited for: ASSOCIATION OF VARIANT ALA-12 WITH CIMT;

Effects of peroxisome proliferator-activated receptor-gamma 2 Pro12Ala polymorphism on body fat distribution in female Korean subjects.
Kim K.S.; Choi S.M.; Shin S.U.; Yang H.S.; Yoon Y.;
Metabolism 53:1538-1543(2004)
Cited for: VARIANT ALA-12;

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.