LH3 PRO270LEU
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.	SiMPLOD3-1151
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.809C>T mutation	PLOD3 NM_001084.4:c.809C>T - NCBI RefSeq NCBI ClinVar: 623469
Mutation type   Current information about the clinical implications of the mutation	Pathogenic
Disease Phenotype   Annotated information about disease phenotypes associated to this mutation	Stickler syndrome type VII (vascular type) Link1 Link2 Link3 Link4
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: 108300 Orphanet: ORPHA:828 ICD-10: Q87.8 MeSH: C537492
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 MAY EXIST at the protein level, although no experimental evidence is currently available to support its existence.
References   Publications (and associated links) describing the mutation	Ewans et al, 2019 - DOI - PubMed
Notes from publications   A curated excerpt with information about the mutation from the publications found above	The altered proline residue is highly conserved and located in close proximity to an alpha-helix that interconnects the N-terminal glycosyltransferase (GT) domain with the accessory (AC) domain. Whilst Pro270 is located at a distance and orientation that make it unlikely to be directly involved in GT or GGT reactions, the region incorporating this residue constitutes one of the distinguishing loops that uniquely shape the LH3 GT domain10 and may represent a critical binding site for either collagen substrates or interacting macromolecular partners critical for its correct subcellular trafficking or enzyme function. Computational modeling of the Pro270Leu mutation in an LH3 molecular structure did not show significant perturbations. The Pro270Leu variant seems to reduce at least the glucosyltransferase activity (GGT) of the mutant LH3 enzyme, whereas no sound conclusions can be drawn on the galactosyl-transferase activity (GT). Analysis of the pyridinoline crosslinks of collagen on unhydrolyzed urine showed that the glucosyl-galactosyl- hydroxylysylpyridinoline (GGHP) to hydroxylysylpyridinoline (HP) ratio was slightly reduced.
Related Entries   A list of related LH/PLOD variants found matching the structural position of the mutation currently visualized	SiMPLOD1-160: LH1 PRO258PRO (Likely benign) SiMPLOD1-753: LH1 PRO258LEU (Uncertain significance)
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)