UniProtKB/Swiss-Prot Q8IV16 : Variant p.Thr108Arg
Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1
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Variant information
Variant position:
108
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
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. ]
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:
108 (T108R, p.Thr108Arg).
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:
The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:
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).following page
Variant description:
Any additional useful information about the variant.
Sequence information
Variant position:
108
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:
184
The length of the canonical sequence.
Location on the sequence:
T WCTDSCQPITKTVEGTQVTM
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 T-CTTLIAHGNTESGLLTTHST WCTDSCQPITKTVEGTQVTM
Mouse PFCITLVSHSGTDKGYLTTYSM WCTDTCQPIIKTVGGTQMT
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
21 – 151 Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1
Domain
63 – 148 UPAR/Ly6
Region
103 – 109 Important for interaction with LPL
Disulfide bond
83 – 110
Mutagenesis
91 – 91 T -> A. Promotes formation of dimers and oligomers reducing number of monomers.
Mutagenesis
92 – 92 L -> A. Only slightly increased formation of dimers and oligomers. No effect on number of monomers. Loss of LPL interaction.
Mutagenesis
93 – 93 I -> A. Promotes formation of dimers and oligomers reducing number of monomers.
Mutagenesis
101 – 101 G -> S. Promotes formation of dimers and oligomers reducing number of monomers. Retained some interaction with LPL.
Mutagenesis
104 – 104 T -> A. Promotes formation of dimers and oligomers reducing number of monomers. Retained some interaction with LPL.
Mutagenesis
105 – 105 T -> A. Promotes formation of dimers and oligomers reducing number of monomers.
Mutagenesis
106 – 106 H -> L. Promotes formation of dimers and oligomers severely reducing number of monomers.
Mutagenesis
107 – 107 S -> A. Promotes formation of dimers and oligomers reducing number of monomers.
Mutagenesis
108 – 108 T -> A. Retained some interaction with LPL. No effect on number of monomers.
Mutagenesis
109 – 109 W -> CPT. Promotes formation of dimers and oligomers reducing number of monomers. Loss of LPL interaction.
Mutagenesis
109 – 109 W -> SYHAF. Loss of interaction with LPL. Only slightly increased formation of dimers and oligomers. No effect on number of monomers.
Mutagenesis
115 – 115 Q -> K. No effect on number of monomers.
Mutagenesis
126 – 126 V -> A. Promotes formation of dimers and oligomers reducing number of monomers.
Beta strand
101 – 113
Literature citations
Mutations in LPL, APOC2, APOA5, GPIHBP1 and LMF1 in patients with severe hypertriglyceridaemia.
Surendran R.P.; Visser M.E.; Heemelaar S.; Wang J.; Peter J.; Defesche J.C.; Kuivenhoven J.A.; Hosseini M.; Peterfy M.; Kastelein J.J.; Johansen C.T.; Hegele R.A.; Stroes E.S.; Dallinga-Thie G.M.;
J. Intern. Med. 272:185-196(2012)
Cited for: VARIANTS HLPP1D TYR-65; ARG-108; PRO-115 AND PHE-144;
GPIHBP1 missense mutations often cause multimerization of GPIHBP1 and thereby prevent lipoprotein lipase binding.
Beigneux A.P.; Fong L.G.; Bensadoun A.; Davies B.S.; Oberer M.; Gaardsvoll H.; Ploug M.; Young S.G.;
Circ. Res. 116:624-632(2015)
Cited for: CHARACTERIZATION OF VARIANTS HLPP1D SER-65; TYR-65; ARG-68; GLY-68; TYR-68; PHE-89; ARG-108 AND PRO-115; SUBUNIT; INTERACTION WITH LPL; MUTAGENESIS OF TYR-66; LEU-71; THR-91; LEU-92; ILE-93; GLY-101; THR-104; THR-105; HIS-106; SER-107; THR-108; TRP-109; GLN-115 AND VAL-126;
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.
