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UniProtKB/Swiss-Prot P01130: Variant p.Pro826Ser

Low-density lipoprotein receptor
Gene: LDLR
Variant information

Variant position:  826
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
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 Proline (P) to Serine (S) at position 826 (P826S, p.Pro826Ser).
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 polar (S)
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

Variant description:  In FHCL1.
Any additional useful information about the variant.

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



Sequence information

Variant position:  826
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  860
The length of the canonical sequence.

Location on the sequence:   VFLLWKNWRLKNINSINFDN  P VYQKTTEDEVHICHNQDGYS
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                         VFLLWKNWRLKNINSINFDNPVYQKTTEDEVHICHNQDGYS

Mouse                         AVLLWRNWRLKNINSINFDNPVYQKTTEDELHICRSQDGYT

Rat                           AILLWRNWRLRNINSINFDNPVYQKTTEDEIHICRSQDGYT

Bovine                        TFLLWKNWRLKSINSINFDNPVYQKTTEDEVHICRSQDGYT

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 22 – 860 Low-density lipoprotein receptor
Topological domain 811 – 860 Cytoplasmic
Region 811 – 860 Required for MYLIP-triggered down-regulation of LDLR
Motif 823 – 828 NPXY motif
Mutagenesis 811 – 811 K -> R. No change. No change; when associated with R-816 and R-830. Insensitive to MYLIP-triggered degradation; when associated with R-816; R-830 and A-839.
Mutagenesis 816 – 816 K -> R. No change. No change; when associated with R-830. No change; when associated with R-811 and R-830. Insensitive to MYLIP-triggered degradation; when associated with R-830 and A-839. Insensitive to MYLIP-triggered degradation; when associated with R-811; R-830 and A-839.
Mutagenesis 821 – 821 I -> A. 3-fold decreased affinity for LDLRAP1.
Mutagenesis 821 – 821 I -> R. 10-fold decreased affinity for LDLRAP1.
Mutagenesis 828 – 828 Y -> A. Abolishes interaction with ARRB2.
Mutagenesis 829 – 829 Q -> A. Decreased affinity for LDLRAP1.
Mutagenesis 830 – 830 K -> R. No change. No change; when associated with R-816. No change; when associated with R-811 and R-816. Insensitive to MYLIP-triggered degradation; when associated with A-839. Insensitive to MYLIP-triggered degradation; when associated with R-816 and A-839. Insensitive to MYLIP-triggered degradation; when associated with R-811; R-816 and A-839.
Mutagenesis 839 – 839 C -> A. No change. Insensitive to MYLIP-triggered degradation; when associated with R-830. Insensitive to MYLIP-triggered degradation; when associated with R-816 and R-830. Insensitive to MYLIP-triggered degradation; when associated with R-811; R-816 and R-830.
Turn 826 – 829


Literature citations

The molecular basis of familial hypercholesterolemia in Lebanon: spectrum of LDLR mutations and role of PCSK9 as a modifier gene.
Abifadel M.; Rabes J.-P.; Jambart S.; Halaby G.; Gannage-Yared M.-H.; Sarkis A.; Beaino G.; Varret M.; Salem N.; Corbani S.; Aydenian H.; Junien C.; Munnich A.; Boileau C.;
Hum. Mutat. 30:E682-E691(2009)
Cited for: VARIANTS FHCL1 PRO-254; TYR-356; TYR-358; THR-451 AND SER-826;

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.