UniProtKB/Swiss-Prot Q9BY76: Variant p.Glu40Lys

Angiopoietin-related protein 4
Gene: ANGPTL4
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Variant information Variant position:

40 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 Glutamate (E) to Lysine (K) at position 40 (E40K, p.Glu40Lys). 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 acidic (E) to large size and basic (K) 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 ANGPTL4 are associated with low plasma triglyceride levels and define the plasma triglyceride level quantitative trait locus (TGQTL) [MIM:615881]. Additional information on the polymorphism described.
Variant description:

Associated with lower plasma levels of triglyceride and higher levels of HDL cholesterol; strongly reduced inactivation of lipoprotein lipase LPL; no effect on protein secretion and stability of monomers; abolishes accumulation of oligomers. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs116843064 [ dbSNP | Ensembl ]

Sequence information Variant position:

40 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

406 The length of the canonical sequence.
Location on the sequence:

LLSAQGGPVQSKSPRFASWD E MNVLAHGLLQLGQGLREHAE 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                         LLSAQGGPVQSKSPRFASWDEMNVLAHGLLQLGQGLREHAE

Mouse                         LLSAQGRPAQPEPPRFASWDEMNLLAHGLLQLGHGLREHVE

Rat                           LLSAQGRPAQPEPPRFASWDEMNLLAHGLLQLGHGLREHVE

Pig                           LLSAQGSPEPPEAPRFASWDEVNVLAHGLLQLGRGLREHVE

Bovine                        LLSAQGRPEPPETPRFASWDEVNVLAHGLLQLGHGLREHVE

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	26 – 406	Angiopoietin-related protein 4
Chain	26 – 163	ANGPTL4 N-terminal chain
Alternative sequence	1 – 167	Missing. In isoform 3.
Mutagenesis	40 – 40	E -> A. Loss of inactivation of lipoprotein lipase LPL.
Mutagenesis	40 – 40	E -> D. Decreased inactivation of lipoprotein lipase LPL.

Literature citations
Genetic variation in ANGPTL4 provides insights into protein processing and function.
Yin W.; Romeo S.; Chang S.; Grishin N.V.; Hobbs H.H.; Cohen J.C.;
J. Biol. Chem. 284:13213-13222(2009)
Cited for: SUBCELLULAR LOCATION; SUBUNIT; PROTEOLYTIC CLEAVAGE; CHARACTERIZATION OF VARIANT LYS-40; MUTAGENESIS OF GLU-40; CYS-76; CYS-80 AND 161-ARG--ARG-164; DISULFIDE BONDS; The angiopoietin-like protein ANGPTL4 catalyzes unfolding of the hydrolase domain in lipoprotein lipase and the endothelial membrane protein GPIHBP1 counteracts this unfolding.
Mysling S.; Kristensen K.K.; Larsson M.; Kovrov O.; Bensadouen A.; Joergensen T.J.; Olivecrona G.; Young S.G.; Ploug M.;
Elife 5:0-0(2016)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT LYS-40; Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL.
Romeo S.; Pennacchio L.A.; Fu Y.; Boerwinkle E.; Tybjaerg-Hansen A.; Hobbs H.H.; Cohen J.C.;
Nat. Genet. 39:513-516(2007)
Cited for: ASSOCIATION WITH TGQTL; VARIANTS LEU-5; LYS-40; ILE-41; ARG-67; LEU-72; ARG-77; LYS-167; SER-174; GLN-190; LYS-196; CYS-230; ARG-233; VAL-237; THR-251; MET-266; GLN-278; MET-291; MET-293; VAL-296; SER-307; MET-308; CYS-336; GLU-338; CYS-349; SER-361; ARG-361; GLN-371 AND TRP-384; Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes.
Gusarova V.; O'Dushlaine C.; Teslovich T.M.; Benotti P.N.; Mirshahi T.; Gottesman O.; Van Hout C.V.; Murray M.F.; Mahajan A.; Nielsen J.B.; Fritsche L.; Wulff A.B.; Gudbjartsson D.F.; Sjoegren M.; Emdin C.A.; Scott R.A.; Lee W.J.; Small A.; Kwee L.C.; Dwivedi O.P.; Prasad R.B.; Bruse S.; Lopez A.E.; Penn J.; Marcketta A.; Leader J.B.; Still C.D.; Kirchner H.L.; Mirshahi U.L.; Wardeh A.H.; Hartle C.M.; Habegger L.; Fetterolf S.N.; Tusie-Luna T.; Morris A.P.; Holm H.; Steinthorsdottir V.; Sulem P.; Thorsteinsdottir U.; Rotter J.I.; Chuang L.M.; Damrauer S.; Birtwell D.; Brummett C.M.; Khera A.V.; Natarajan P.; Orho-Melander M.; Flannick J.; Lotta L.A.; Willer C.J.; Holmen O.L.; Ritchie M.D.; Ledbetter D.H.; Murphy A.J.; Borecki I.B.; Reid J.G.; Overton J.D.; Hansson O.; Groop L.; Shah S.H.; Kraus W.E.; Rader D.J.; Chen Y.I.; Hveem K.; Wareham N.J.; Kathiresan S.; Melander O.; Stefansson K.; Nordestgaard B.G.; Tybjaerg-Hansen A.; Abecasis G.R.; Altshuler D.; Florez J.C.; Boehnke M.; McCarthy M.I.; Yancopoulos G.D.; Carey D.J.; Shuldiner A.R.; Baras A.; Dewey F.E.; Gromada J.;
Nat. Commun. 9:2252-2252(2018)
Cited for: VARIANT LYS-40; SUBCELLULAR LOCATION; TISSUE SPECIFICITY;

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.