UniProtKB/Swiss-Prot Q9NST1: Variant p.Ile148Met

1-acylglycerol-3-phosphate O-acyltransferase PNPLA3
Gene: PNPLA3
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Variant information Variant position:

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

LB/B 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 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:

Associated with increased hepatic fat content and serum aspartate aminotransferase concentrations; probable gain-of-function variant; 2-fold increase in 1-acylglycerol-3-phosphate O-acyltransferase/lysophosphatidic acid acyltransferase activity; results on glycerolipid hydrolysis activity are controversial with reduction in triacylglycerol, diacylglycerol and monoacylglycerol hydrolase activity or no effect compared to wild-type in which this activity may be very low; does not affect subcellular location, nor association with lipid droplets. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs738409 [ dbSNP | Ensembl ]

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.

Type	Positions	Description
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; 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; A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis.
He S.; McPhaul C.; Li J.Z.; Garuti R.; Kinch L.; Grishin N.V.; Cohen J.C.; Hobbs H.H.;
J. Biol. Chem. 285:6706-6715(2010)
Cited for: CATALYTIC ACTIVITY; FUNCTION; SUBCELLULAR LOCATION; PATHWAY; CHARACTERIZATION OF VARIANT MET-148; Expression and characterization of a PNPLA3 protein isoform (I148M) associated with nonalcoholic fatty liver disease.
Huang Y.; Cohen J.C.; Hobbs H.H.;
J. Biol. Chem. 286:37085-37093(2011)
Cited for: CHARACTERIZATION OF VARIANT MET-148; INVOLVEMENT IN SUSCEPTIBILITY TO NAFLD1; CATALYTIC ACTIVITY; FUNCTION; BIOPHYSICOCHEMICAL PROPERTIES; MUTAGENESIS OF SER-47; 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;

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.