UniProtKB/SwissProt variant VAR

Variant information

Variant position:

685

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 Leucine (L) at position 685 (P685L, p.Pro685Leu).

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:

-3

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; Gujerat/Zambia/Belgian/Dutch/Sweden/Japan.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs28942084 [ dbSNP | Ensembl ]

Sequence information

Variant position:

685

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:

NWCERTTLSNGGCQYLCLPA P QINPHSPKFTCACPDGMLLA

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                         NWCERTTL-SNGGCQYLCLPAPQINPHSPKFTCACPDGMLLA

Mouse                         NWCETTALLPNGGCQYLCLPAPQIGPHSPKFTCACPDGMLL

Rat                           NWCEATVL-PNGGCQYMCLPAPQISAHSPKFTCACPDGMLL

Bovine                        NWCERTAL-RNGGCQYLCLPAPQINPRSPKFTCACPDGMLL

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	22 – 788	Extracellular
Domain	663 – 712	EGF-like 3
Disulfide bond	677 – 696
Alternative sequence	663 – 713	Missing. In isoform 2.

Literature citations

Identification of a point mutation in growth factor repeat C of the low density lipoprotein-receptor gene in a patient with homozygous familial hypercholesterolemia that affects ligand binding and intracellular movement of receptors.
Soutar A.K.; Knight B.L.; Patel D.D.;
Proc. Natl. Acad. Sci. U.S.A. 86:4166-4170(1989)
Cited for: VARIANT FHCL1 LEU-685;

Identification and properties of the proline664-leucine mutant LDL receptor in South Africans of Indian origin.
Rubinsztein D.C.; Coetzee G.A.; Marais A.D.; Leitersdorf E.; Seftel H.C.; van der Westhuyzen D.R.;
J. Lipid Res. 33:1647-1655(1992)
Cited for: VARIANT FHCL1 LEU-685;

Common mutations in the low-density-lipoprotein-receptor gene causing familial hypercholesterolemia in the Japanese population.
Maruyama T.; Miyake Y.; Tajima S.; Harada-Shiba M.; Yamamura T.; Tsushima M.; Kishino B.; Horiguchi Y.; Funahashi T.; Matsuzawa Y.; Yamamoto A.;
Arterioscler. Thromb. Vasc. Biol. 15:1713-1718(1995)
Cited for: VARIANTS FHCL1 LYS-140; SER-338 AND LEU-685;

Mutational and genetic origin of LDL receptor gene mutations detected in both Belgian and Dutch familial hypercholesterolemics.
Peeters A.V.; van Gaal L.F.; du Plessis L.; Lombardi M.P.R.; Havekes L.M.; Kotze M.J.;
Hum. Genet. 100:266-270(1997)
Cited for: VARIANT FHCL1 LEU-685;

Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk.
Humphries S.E.; Whittall R.A.; Hubbart C.S.; Maplebeck S.; Cooper J.A.; Soutar A.K.; Naoumova R.; Thompson G.R.; Seed M.; Durrington P.N.; Miller J.P.; Betteridge D.J.B.; Neil H.A.W.;
J. Med. Genet. 43:943-949(2006)
Cited for: VARIANTS FHCL1 TYR-89; LYS-101; GLY-218 DEL; GLY-221; ASN-221; TYR-358; PRO-479; HIS-482; ARG-677 AND LEU-685; FUNCTION;

Diagnosis of families with familial hypercholesterolaemia and/or Apo B-100 defect by means of DNA analysis of LDL-receptor gene mutations.
Widhalm K.; Dirisamer A.; Lindemayr A.; Kostner G.;
J. Inherit. Metab. Dis. 30:239-247(2007)
Cited for: VARIANTS FHCL1 THR-50; LEU-211; GLY-221; GLU-266; LYS-277; ARG-286; ARG-314; ARG-352; LYS-408; THR-431; HIS-442; MET-523; GLY-577; THR-585 AND LEU-685;

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.Pro685Leu