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UniProtKB/Swiss-Prot P04180: Variant p.Arg347Cys

Phosphatidylcholine-sterol acyltransferase
Gene: LCAT
Variant information

Variant position:  347
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 Arginine (R) to Cysteine (C) at position 347 (R347C, p.Arg347Cys).
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 (C)
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

Involvement in disease:  Fish-eye disease (FED) [MIM:136120]: A disorder of lipoprotein metabolism due to partial lecithin-cholesterol acyltransferase deficiency that affects only alpha-LCAT activity. FED is characterized by low plasma HDL and corneal opacities due to accumulation of cholesterol deposits in the cornea ('fish-eye'). {ECO:0000269|PubMed:1516702, ECO:0000269|PubMed:1571050, ECO:0000269|PubMed:15994445, ECO:0000269|PubMed:1737840, ECO:0000269|PubMed:21901787, ECO:0000269|PubMed:8620346, ECO:0000269|PubMed:9261271}. 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 FED; results in reduced activity.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  347
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  440
The length of the canonical sequence.

Location on the sequence:   GLPAPGVEVYCLYGVGLPTP  R TYIYDHGFPYTDPVGVLYED
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                         GLPAPGVEVYCLYGVGLPTPRTYIYDHGFPYTDPVGVLYED

Mouse                         RLPAPGVEVYCLYGVGRPTPHTYIYDHNFPYKDPVAALYED

Rat                           GLPAPGVEVYCLYGVGMPTAHTYIYDHNFPYKDPVAALYED

Rabbit                        GLPAPGVEVYCLYGIGLPTPHTYIYDHGFPYTDPVGVLYED

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 25 – 440 Phosphatidylcholine-sterol acyltransferase
Disulfide bond 337 – 380
Beta strand 335 – 350


Literature citations

High prevalence of mutations in LCAT in patients with low HDL cholesterol levels in The Netherlands: identification and characterization of eight novel mutations.
Holleboom A.G.; Kuivenhoven J.A.; Peelman F.; Schimmel A.W.; Peter J.; Defesche J.C.; Kastelein J.J.; Hovingh G.K.; Stroes E.S.; Motazacker M.M.;
Hum. Mutat. 32:1290-1298(2011)
Cited for: VARIANTS 134-GLU-TYR-135 DELINS ASP-ASN; PHE-246; CYS-268 AND CYS-322; VARIANTS FED SER-99; PHE-338 AND CYS-347; CHARACTERIZATION OF VARIANTS 134-GLU-TYR-135 DELINS ASP-ASN; PHE-246; CYS-268 AND CYS-322; CHARACTERIZATION OF VARIANTS FED SER-99; PHE-338 CYS-347 AND CYS-347;

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.