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UniProtKB/Swiss-Prot Q9NST1: Variant p.Ile148Met

1-acylglycerol-3-phosphate O-acyltransferase PNPLA3
Gene: PNPLA3
Chromosomal location: 22q13.31
Variant information

Variant position:  148
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 Isoleucine (I) to Methionine (M) at position 148 (I148M, p.Ile148Met).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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:  Polymorphic variation at position 148 influences insulin secretion levels and obesity. In obese subjects the body mass index and waist are higher in carriers of the Ile-148 allele. The Ile-148 carriers also display decreased insulin secretion in response to oral glucose tolerance test. Met-148 allele carriers are seemingly more insulin resistant at a lower body mass index.
Additional information on the polymorphism described.

Variant description:  Common polymorphism; associated with increased hepatic fat content and serum aspartate aminotransferase concentrations; increases 1-acylglycerol-3-phosphate O-acyltransferase activity 2-fold.
Any additional useful information about the variant.

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



Sequence information

Variant position:  148
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  481
The length of the canonical sequence.

Location on the sequence:   LVSDFRSKDEVVDALVCSCF  I PFYSGLIPPSFRGVRYVDGG
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                         LVSDFRSKDEVVDALVCSCFIPFYSGLIPPSFRGVRYVDGG

Mouse                         LVSEFHSKDEVVDALVCSCFIPLFSGLIPPSFRGERYVDGG

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 – 481 1-acylglycerol-3-phosphate O-acyltransferase PNPLA3
Topological domain 63 – 481 Lumenal
Domain 10 – 179 PNPLA
Active site 166 – 166 Proton acceptor


Literature citations

Complete sequencing and characterization of 21,243 full-length human cDNAs.
Ota T.; Suzuki Y.; Nishikawa T.; Otsuki T.; Sugiyama T.; Irie R.; Wakamatsu A.; Hayashi K.; Sato H.; Nagai K.; Kimura K.; Makita H.; Sekine M.; Obayashi M.; Nishi T.; Shibahara T.; Tanaka T.; Ishii S.; Yamamoto J.; Saito K.; Kawai Y.; Isono Y.; Nakamura Y.; Nagahari K.; Murakami K.; Yasuda T.; Iwayanagi T.; Wagatsuma M.; Shiratori A.; Sudo H.; Hosoiri T.; Kaku Y.; Kodaira H.; Kondo H.; Sugawara M.; Takahashi M.; Kanda K.; Yokoi T.; Furuya T.; Kikkawa E.; Omura Y.; Abe K.; Kamihara K.; Katsuta N.; Sato K.; Tanikawa M.; Yamazaki M.; Ninomiya K.; Ishibashi T.; Yamashita H.; Murakawa K.; Fujimori K.; Tanai H.; Kimata M.; Watanabe M.; Hiraoka S.; Chiba Y.; Ishida S.; Ono Y.; Takiguchi S.; Watanabe S.; Yosida M.; Hotuta T.; Kusano J.; Kanehori K.; Takahashi-Fujii A.; Hara H.; Tanase T.-O.; Nomura Y.; Togiya S.; Komai F.; Hara R.; Takeuchi K.; Arita M.; Imose N.; Musashino K.; Yuuki H.; Oshima A.; Sasaki N.; Aotsuka S.; Yoshikawa Y.; Matsunawa H.; Ichihara T.; Shiohata N.; Sano S.; Moriya S.; Momiyama H.; Satoh N.; Takami S.; Terashima Y.; Suzuki O.; Nakagawa S.; Senoh A.; Mizoguchi H.; Goto Y.; Shimizu F.; Wakebe H.; Hishigaki H.; Watanabe T.; Sugiyama A.; Takemoto M.; Kawakami B.; Yamazaki M.; Watanabe K.; Kumagai A.; Itakura S.; Fukuzumi Y.; Fujimori Y.; Komiyama M.; Tashiro H.; Tanigami A.; Fujiwara T.; Ono T.; Yamada K.; Fujii Y.; Ozaki K.; Hirao M.; Ohmori Y.; Kawabata A.; Hikiji T.; Kobatake N.; Inagaki H.; Ikema Y.; Okamoto S.; Okitani R.; Kawakami T.; Noguchi S.; Itoh T.; Shigeta K.; Senba T.; Matsumura K.; Nakajima Y.; Mizuno T.; Morinaga M.; Sasaki M.; Togashi T.; Oyama M.; Hata H.; Watanabe M.; Komatsu T.; Mizushima-Sugano J.; Satoh T.; Shirai Y.; Takahashi Y.; Nakagawa K.; Okumura K.; Nagase T.; Nomura N.; Kikuchi H.; Masuho Y.; Yamashita R.; Nakai K.; Yada T.; Nakamura Y.; Ohara O.; Isogai T.; Sugano S.;
Nat. Genet. 36:40-45(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2); VARIANTS CYS-115; MET-148 AND GLU-434;

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
The MGC Project Team;
Genome Res. 14:2121-2127(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1); VARIANTS GLY-99; MET-148 AND GLU-434;

Adiponutrin functions as a nutritionally regulated lysophosphatidic acid acyltransferase.
Kumari M.; Schoiswohl G.; Chitraju C.; Paar M.; Cornaciu I.; Rangrez A.Y.; Wongsiriroj N.; Nagy H.M.; Ivanova P.T.; Scott S.A.; Knittelfelder O.; Rechberger G.N.; Birner-Gruenberger R.; Eder S.; Brown H.A.; Haemmerle G.; Oberer M.; Lass A.; Kershaw E.E.; Zimmermann R.; Zechner R.;
Cell Metab. 15:691-702(2012)
Cited for: FUNCTION; CATALYTIC ACTIVITY; CHARACTERIZATION OF VARIANT MET-148; MUTAGENESIS OF CYS-15; SER-47; ASP-206 AND PRO-311; PATHWAY; SUBCELLULAR LOCATION; CAUTION;

Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity.
Johansson L.E.; Lindblad U.; Larsson C.A.; Raastam L.; Ridderstraale M.;
Eur. J. Endocrinol. 159:577-583(2008)
Cited for: VARIANT MET-148; POLYMORPHISM;

Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease.
Romeo S.; Kozlitina J.; Xing C.; Pertsemlidis A.; Cox D.; Pennacchio L.A.; Boerwinkle E.; Cohen J.C.; Hobbs H.H.;
Nat. Genet. 40:1461-1465(2008)
Cited for: VARIANTS MET-148 AND ILE-453; INVOLVEMENT IN SUSCEPTIBILITY TO NAFLD1;

A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans.
Kotronen A.; Johansson L.E.; Johansson L.M.; Roos C.; Westerbacka J.; Hamsten A.; Bergholm R.; Arkkila P.; Arola J.; Kiviluoto T.; Fisher R.M.; Ehrenborg E.; Orho-Melander M.; Ridderstrale M.; Groop L.; Yki-Jarvinen H.;
Diabetologia 52:1056-1060(2009)
Cited for: VARIANT MET-148; INVOLVEMENT IN SUSCEPTIBILITY TO NAFLD1;

A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity.
Sookoian S.; Castano G.O.; Burgueno A.L.; Gianotti T.F.; Rosselli M.S.; Pirola C.J.;
J. Lipid Res. 50:2111-2116(2009)
Cited for: VARIANT MET-148; INVOLVEMENT IN SUSCEPTIBILITY TO NAFLD1;

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.