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UniProtKB/Swiss-Prot P01130: Variant p.Asp172Asn

Low-density lipoprotein receptor
Gene: LDLR
Variant information

Variant position:  172
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

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

Involvement in disease:  Familial hypercholesterolemia (FH) [MIM:143890]: A common autosomal dominant disorder characterized by elevated serum low-density lipoprotein (LDL) cholesterol levels, which result in excess deposition of cholesterol in tissues and leads to xanthelasma, xanthomas, accelerated atherosclerosis and increased risk of premature coronary heart disease. The disorder occurs in 2 clinical forms: a mild form that becomes evident in the fourth or fifth decade in individuals carrying heterozygous LDLR mutations; a more severe form that usually manifests in the first two decades of life in individuals with homozygous LDLR mutations. {ECO:0000269|PubMed:10090484, ECO:0000269|PubMed:10206683, ECO:0000269|PubMed:10422803, ECO:0000269|PubMed:10447263, ECO:0000269|PubMed:10532689, ECO:0000269|PubMed:10660340, ECO:0000269|PubMed:10882754, ECO:0000269|PubMed:10978268, ECO:0000269|PubMed:10980548, ECO:0000269|PubMed:11298688, ECO:0000269|PubMed:11462246, ECO:0000269|PubMed:1446662, ECO:0000269|PubMed:1464748, ECO:0000269|PubMed:17142622, ECO:0000269|PubMed:17347910, ECO:0000269|PubMed:1867200, ECO:0000269|PubMed:19318025, ECO:0000269|PubMed:19319977, ECO:0000269|PubMed:22160468, ECO:0000269|PubMed:22509010, ECO:0000269|PubMed:2318961, ECO:0000269|PubMed:24529145, ECO:0000269|PubMed:25378237, ECO:0000269|PubMed:25545329, ECO:0000269|PubMed:2569482, ECO:0000269|PubMed:2726768, ECO:0000269|PubMed:3263645, ECO:0000269|PubMed:3955657, ECO:0000269|PubMed:7550239, ECO:0000269|PubMed:7573037, ECO:0000269|PubMed:7583548, ECO:0000269|PubMed:7635461, ECO:0000269|PubMed:7635482, ECO:0000269|PubMed:7649546, ECO:0000269|PubMed:7649549, ECO:0000269|PubMed:8168830, ECO:0000269|PubMed:8347689, ECO:0000269|PubMed:8462973, ECO:0000269|PubMed:8664907, ECO:0000269|PubMed:8740918, ECO:0000269|PubMed:9026534, ECO:0000269|PubMed:9104431, ECO:0000269|PubMed:9143924, ECO:0000269|PubMed:9254862, ECO:0000269|PubMed:9259195, ECO:0000269|PubMed:9452094, ECO:0000269|PubMed:9452095, ECO:0000269|PubMed:9452118, ECO:0000269|PubMed:9654205, ECO:0000269|PubMed:9678702, ECO:0000269|PubMed:9852677, ECO:0000269|Ref.71}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In FH; 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.



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.

TypePositionsDescription
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 FH 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 FH ARG-116; ASN-168; ASN-172; GLY-300 AND GLY-301; CHARACTERIZATION OF VARIANT TRP-257;

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.