UniProtKB/Swiss-Prot Q9UHC9: Variant p.Ile1233Asn

NPC1-like intracellular cholesterol transporter 1
Gene: NPC1L1
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Variant information Variant position:

1233 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Isoleucine (I) to Asparagine (N) at position 1233 (I1233N, p.Ile1233Asn). 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 (I) to medium size and polar (N) 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
Polymorphism:

Genetic variations in NPC1L1 influence low density lipoprotein cholesterol (LDL-C) content defining the low density lipoprotein cholesterol level quantitative trait locus 7 (LDLCQ7) [MIM:617966]. Inactivating variants may confer a lower risk of coronary heart disease (PubMed:25390462). Rare NPC1L1 variants also influence response to ezetimibe, a drug that reduces plasma LDL-C by blocking sterol absorption in enterocytes (PubMed:15679830). Additional information on the polymorphism described.
Variant description:

Found in a non-responder to ezetimibe treatment. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs52815063 [ dbSNP | Ensembl ]

Sequence information Variant position:

1233 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1359 The length of the canonical sequence.
Location on the sequence:

TRSFAISTKPTWLERAKEAT I SMGSAVFAGVAMTNLPGILV 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                         TRSFAISTKPTWLERAKEATISMGSAVFAGVAMTNLPGILV

Mouse                         TRSFAVSTKPTRLERAKDATIFMGSAVFAGVAMTNFPGILI

Rat                           TRSFAVSTKPTRLERAKDATVFMGSAVFAGVAMTNFPGILI

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 – 1359	NPC1-like intracellular cholesterol transporter 1
Topological domain	1213 – 1236	Cytoplasmic
Alternative sequence	725 – 1359	Missing. In isoform 3.
Helix	1224 – 1252

Literature citations
Compound heterozygosity for two non-synonymous polymorphisms in NPC1L1 in a non-responder to ezetimibe.
Wang J.; Williams C.M.; Hegele R.A.;
Clin. Genet. 67:175-177(2005)
Cited for: VARIANTS LEU-55 AND ASN-1233; POLYMORPHISM;

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.