LH1 ARG319END
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.	SiMPLOD1-35
Isoenzyme   Follow the links to gather information about the LH1 isoenzyme	Lysyl Hydroxylase 1 (human) - UniProt - Full Info
Nucleotide mutation   Follow the links to explore annotated information about the significance of the PLOD1 c.955C>T mutation	PLOD1 NM_000302.2:c.955C>T - NCBI RefSeq NCBI SNP: rs121913550 NCBI ClinVar: 14364
Mutation type   Current information about the clinical implications of the mutation	Pathogenic
LOVD   Link to Leiden Open Variation Database (LOVD)	c.955C>T
Disease Phenotype   Annotated information about disease phenotypes associated to this mutation	no disease phenotype information available
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	Warning: this variant incorporates a premature truncation of the aminoacid sequence at residue 319, and may result in misfolding and/or complete absence of the enzyme. This variant is EXTREMELY UNLIKELY to be compatible with a folded LH enzyme. The representation shown in the structure viewer is therefore for mere display purposes and does not refer to an actual predicted existing protein product.
References   Publications (and associated links) describing the mutation	Hyland et al., 1992 - DOI - PubMed Eyre et al., 2002 - DOI - PubMed Giunta et al., 2005 - DOI - PubMed Steinmann et al., 1995 - PubMed al-Gazali et al., 1997 - DOI - PubMed Royce et al. 1985 - DOI - PubMed
Notes from publications   A curated excerpt with information about the mutation from the publications found above	Hyland et al. first reported in two siblings with EDS type VI on the single basepair substitution converting the CGA codon (Arg319) to a TGA termination codon. The healthy parents were first cousins, and two of the three healthy siblings of the patients are heterozygous for the mutation. The authors demonstrated a total loss of lysyl hydroxylase activity in extracts derived from fibroblasts of the patients. Eyre et al. analyzed the urine of a patient bearing Arg319End mutation showing the lack of hydroxylation of the helical lysines at residues 930 of alpha 1(I) and 933 of alpha 2(I) of the collagen triple-helix. This mutation was also identified by Giunta et al. in the mutation analysis of PLOD1 gene. The phenotype associated to this variant was also reported as Nevo Syndrome, now merged with Kyphoscholiotic Ehlers-Danlos (type VIa) syndrome.
Structural Observations   An evaluation of the possible effects/implications of the mutations on the LH1 molecular structure
Related Entries   A list of related LH/PLOD variants found matching the structural position of the mutation currently visualized	SiMPLOD1-319: LH1 delta282-325 (Pathogenic) SiMPLOD1-805: LH1 ARG319GLN (SNP) SiMPLOD1-806: LH1 ARG319LEU (SNP)
Last Update   An evaluation of the possible effects/implications of the mutations on the LH1 molecular structure	2021-06-23 08:38:51
The three-dimensional visualization is currently based on the homology model of full-length, dimeric human LH1 (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): LH1 homology modelLH3 with Fe2+ and 2-OG (PDB 6FXK)