LH2a ARG598HIS (LH2a) - ARG619HIS (LH2b)
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.	SiMPLOD2-229
Isoenzyme   Follow the links to gather information about the LH2a isoenzyme	Lysyl Hydroxylase 2a (human) - UniProt - Full Info
Nucleotide mutation   Follow the links to explore annotated information about the significance of the PLOD2 c.1793G>A mutation	PLOD2 NM_000935.2:c.1793G>A - NCBI RefSeq NCBI SNP: rs121434461 NCBI ClinVar: 7643
Mutation type   Current information about the clinical implications of the mutation	Pathogenic
LOVD   Link to Leiden Open Variation Database (LOVD)	c.1856G>A
Disease Phenotype   Annotated information about disease phenotypes associated to this mutation	Bruck Syndrome (Type II) Link1 Link2
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: 609220 Orphanet: ORPHA:2771 ICD-10: M21.8 MeSH: C537407
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	Ha-Vinh et al., 2004 - DOI - PubMed Hyry et al., 2009 - DOI - PubMed Puig-Hervas et al., 2012 - DOI - PubMed
Notes from publications   A curated excerpt with information about the mutation from the publications found above	Ha-Vinh et al. first described in a patient with Bruck syndrome the homozygous G>A transition at position c.1793-1856 (PLOD2a-PLOD2b). This missense mutation cause the aminoacid substitution Arg598His (Arg619 in PLOD2b). Clinical analysis and biochemical properties of urines are also described. Hyry et al. performed expression and characterization of the recombinant mutant Arg598His. The protein was expressed but high molecular weight aggregates were present even in SDS-PAGE. Decreased affinity for the substrate peptide were shown and the lysyl-hydroxylase activity was below 5% of WT. (Please note that in this publication Arg594 refers to Arg 598 in this database). These findings are consistent with our structural observation and underline the importance of this residue in PLOD catalytic activity.
Structural Observations   An evaluation of the possible effects/implications of the mutations on the LH2a molecular structure	Forms a complex with 2-OG mimicking substrate Lys in metal ion-stabilized structures
Related Entries   A list of related LH/PLOD variants found matching the structural position of the mutation currently visualized	SiMPLOD1-47: LH1 ARG588LEU (Uncertain significance) SiMPLOD1-48: LH1 ARG588HIS (SNP) SiMPLOD1-327: LH1 delta586-634 (Pathogenic) SiMPLOD1-870: LH1 ARG588CYS (SNP) SiMPLOD1-871: LH1 ARG588GLY (SNP) SiMPLOD2-992: LH2a ARG598CYS (SNP) SiMPLOD3-620: LH3 ARG599TRP (SNP) SiMPLOD3-690: LH3 ARG599ARG (SNP) SiMPLOD3-691: LH3 ARG599SER (SNP)
Last Update   An evaluation of the possible effects/implications of the mutations on the LH2a molecular structure	2021-06-23 08:38:51
The three-dimensional visualization is currently based on the homology model of full-length, dimeric human LH2a (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): LH2a homology modelLH2b homology modelLH3 with Fe2+ and 2-OG (PDB 6FXK)