LH3 LEU627PRO
SiMPLOD ID   This is the unique identifier for this mutation in the SiMPLOD database. Please use this identifier when linking information described in SiMPLOD about this mutation.	SiMPLOD3-1147
Isoenzyme   Follow the links to gather information about the LH3 isoenzyme	Lysyl Hydroxylase 3 (human) - UniProt - Full Info
Nucleotide mutation   Follow the links to explore annotated information about the significance of the PLOD3 c.1880T>C mutation	PLOD3 NM_001084.4:c.1880T>C - NCBI RefSeq
Mutation type   Current information about the clinical implications of the mutation	Pathogenic
Disease Phenotype   Annotated information about disease phenotypes associated to this mutation	Epidermolysis Bullosa
Clinical Databases   Link to clinical databases, including OMIM (Online Mendelian Inheritance in Man), Orphanet, ICD-10 (International Statistical Classification of Diseases and Related Health Problems, rev. 10), MeSH (Medical Subject Headings)	OMIM: 131900 Orphanet: ORPHA:508529 ICD-10: Q81.9 MeSH: 68016110
Evidence at protein level   Based on available structural and biochemical information, a statement about the existence of an LH enzyme variant bearing the described mutation is provided	This variant EXISTS at the protein level: published experimental data support its existence as protein product.
LH Activity   When available, biochemical data describing the lysyl hydroxylase activity of the mutant are reported	-
GT/GGT Activity   When available, biochemical data describing the galactosyltransferase (GT) and glucosylgalactosyltransferase (GGT) activities of the mutant are reported	-
References   Publications (and associated links) describing the mutation	Vahidnezhad et al., 2018 - DOI - PubMed
Notes from publications   A curated excerpt with information about the mutation from the publications found above	the Leu627Pro mutation to the C-terminal LH domain of LH3, responsible for lysyl hydroxylase activity. Western blotting of protein synthesized by fibroblasts established from the skin of the patient showed markedly reduced, by ~80%, levels of LH3, when compared to three unaffected controls, whereas the PLOD3mRNA levels in the patient s fibroblasts measured by whole-transcriptome sequencing and confirmed by RT-PCR, were the same as in control cells. the expression of type VII collagen was reduced significantly. Significantly decreased levels of glycosylated hydroxylysine derivatives were noted, with a concomitant relative increase in hydroxylysine
Related Entries   A list of related LH/PLOD variants found matching the structural position of the mutation currently visualized	SiMPLOD1-327: LH1 delta586-634 (Pathogenic) SiMPLOD2-1040: LH2a ILE626THR (SNP)
Last Update   An evaluation of the possible effects/implications of the mutations on the LH3 molecular structure	2021-06-23 08:38:51
The three-dimensional visualization is currently based on the homology model of full-length, dimeric human LH3 (generated using the crystal structure of full-length human LH3 as template). You may select a different PDB model file to visualize the mutation(s) using the drop-down menu below (page will refresh): LH3 homology modelLH3 with Fe2+ and 2-OG (PDB 6FXK)LH3 with Fe2+, 2-OG and Mn2+ (PDB 6FXM)LH3 with Fe2+, 2-OG, Mn2+ and UDP-Gal (PDB 6FXR)LH3 with Fe2+, 2-OG, Mn2+ and UDP-Glc (PDB 6FXT)