UniProtKB/SwissProt variant VAR

Variant information

Variant position:

172

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 Aspartate (D) to Asparagine (N) at position 172 (D172N, p.Asp172Asn).

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 (D) to medium size and polar (N)

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; does not affect receptor expression at the cell surface; results in reduced LDL binding; results in reduced LDL uptake and internalization.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs879254554 [ dbSNP | Ensembl ]

Sequence information

Variant position:

172

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:

SFQCNSSTCIPQLWACDNDP D CEDGSDEWPQRCRGLYVFQG

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                         SFQCNSSTCIPQLWACDNDPDCEDGSDEWPQRCRGLYVFQ--G

Mouse                         HFRCNSSICIPSLWACDGDVDCVDGSDEWPQNCQGRDTASK

Rat                           HFRCNSSSCIPSLWACDGDRDCDDGSDEWPQNCGAEDTAAE

Bovine                        NFQCNSSMCIPQLWACDGDPDCDDGSDEWPKHCGTPHPSGP

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	146 – 186	LDL-receptor class A 4
Glycosylation	156 – 156	N-linked (GlcNAc...) asparagine
Disulfide bond	155 – 173
Disulfide bond	167 – 184
Alternative sequence	105 – 272	Missing. In isoform 3.
Alternative sequence	106 – 232	Missing. In isoform 2.

Literature citations

Spectrum of LDL receptor gene mutations in Denmark: implications for molecular diagnostic strategy in heterozygous familial hypercholesterolemia.
Jensen H.K.; Jensen L.G.; Meinertz H.; Hansen P.S.; Gregersen N.; Faergeman O.;
Atherosclerosis 146:337-344(1999)
Cited for: VARIANTS FHCL1 GLY-87; LYS-140; ASN-172; ARG-243; LEU-306; PRO-404; HIS-564; SER-577; ASN-579; ILE-726 AND LYS-825;

Activity-associated effect of LDL receptor missense variants located in the cysteine-rich repeats.
Etxebarria A.; Benito-Vicente A.; Stef M.; Ostolaza H.; Palacios L.; Martin C.;
Atherosclerosis 238:304-312(2015)
Cited for: CHARACTERIZATION OF VARIANTS FHCL1 ARG-116; ASN-168; ASN-172; GLY-300 AND GLY-301; CHARACTERIZATION OF VARIANT TRP-257;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P01130: Variant p.Asp172Asn