UniProtKB/SwissProt variant VAR

Variant information

Variant position:

814

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

Type of variant:

US

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 Arginine (R) to Glutamine (Q) at position 814 (R814Q, p.Arg814Gln).

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 large size and basic (R) to medium size and polar (Q)

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; unknown pathological significance.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs5928 [ dbSNP | Ensembl ]

Sequence information

Variant position:

814

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:

LPIVLLVFLCLGVFLLWKNW R LKNINSINFDNPVYQKTTED

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                         LPIVLLVFLCLGVFLLWKNWRLKNINSINFDNPVYQKTTED

Mouse                         FPIALVALLVLGAVLLWRNWRLKNINSINFDNPVYQKTTED

Rat                           LPIALVALLVFGAILLWRNWRLRNINSINFDNPVYQKTTED

Bovine                        LPIALLILLAFGTFLLWKNWRLKSINSINFDNPVYQKTTED

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	22 – 860	Low-density lipoprotein receptor
Topological domain	811 – 860	Cytoplasmic
Region	811 – 860	Required for MYLIP-triggered down-regulation of LDLR
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.

Literature citations

Characterization of single-nucleotide polymorphisms in coding regions of human genes.
Cargill M.; Altshuler D.; Ireland J.; Sklar P.; Ardlie K.; Patil N.; Shaw N.; Lane C.R.; Lim E.P.; Kalyanaraman N.; Nemesh J.; Ziaugra L.; Friedland L.; Rolfe A.; Warrington J.; Lipshutz R.; Daley G.Q.; Lander E.S.;
Nat. Genet. 22:231-238(1999)
Cited for: VARIANTS ARG-2; ILE-468 AND GLN-814;

Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia.
Thiart R.; Scholtz C.L.; Vergotine J.; Hoogendijk C.F.; de Villiers J.N.P.; Nissen H.; Brusgaard K.; Gaffney D.; Hoffs M.S.; Vermaak W.J.H.; Kotze M.J.;
J. Med. Genet. 37:514-519(2000)
Cited for: VARIANT FHCL1 47-ASP-GLY-48 DEL; VARIANTS HIS-172; TRP-253; GLN-406; LYS-408; LEU-699 AND GLN-814;

Presence and type of low density lipoprotein receptor (LDLR) mutation influences the lipid profile and response to lipid-lowering therapy in Brazilian patients with heterozygous familial hypercholesterolemia.
Santos P.C.; Morgan A.C.; Jannes C.E.; Turolla L.; Krieger J.E.; Santos R.D.; Pereira A.C.;
Atherosclerosis 233:206-210(2014)
Cited for: VARIANTS FHCL1 TYR-160; ALA-168; LEU-177; TYR-184; GLY-221; GLN-228; LYS-228; TRP-276; TYR-285; GLY-301; PHE-318; CYS-326; SER-343; TYR-368; ASP-373; TRP-406; MET-429; ASN-492; ASP-549; HIS-564; HIS-574; TRP-595; HIS-601; LEU-685; LEU-699; MET-797 AND GLN-814;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P01130: Variant p.Arg814Gln