LH3 ASN223SER
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.	SiMPLOD3-259
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.668A>G mutation	PLOD3 NM_001084.4:c.668A>G - NCBI RefSeq NCBI SNP: rs121434414 NCBI ClinVar: 6643
Mutation type   Current information about the clinical implications of the mutation	Pathogenic
Disease Phenotype   Annotated information about disease phenotypes associated to this mutation	Connective tissue disorder (bone fragility with contractures, arterial rupture, and deafness, resembling to osteogenesis imperfecta) Link1
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: 612394 Orphanet: ORPHA:300284 ICD-10: Q78.0 MeSH: C567320
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	Salo et al., 2008 - DOI - PubMed Scietti et al., 2018 - DOI - PubMed
Notes from publications   A curated excerpt with information about the mutation from the publications found above	The Asn223Ser mutation characterized by one nucleotide transition c.668A/G was first reported by Salo et al. in one male sibling stillborn at 28 weeks gestation. Clinical features are described. The same patient was also characterized by the heterozygous nucleotide deletion c.2071 delT (Cys691Ala-End). Reduced values of glycosyltranferase activity in the serum and in lymphoblastoid cells of the proband was observed. Low PLOD3 protein concentration in lymphoblastoid cells was also described. The recombinant protein with Asn223Ser mutations resulted in higher apparent molecular mass in SDS-PAGE. This difference was not observed after treatment with EndoH (a glycosidase) suggesting that this mutation introduce a new glycosylation site for PLOD3 at Asn221. Scietti et al. mapped the Asn223Ser close to the entrance of the glycosyltranferase catalytic site, suggesting an interference with recognition of acceptor substrate molecules. Structural and biochemical features are described.
Structural Observations   An evaluation of the possible effects/implications of the mutations on the LH3 molecular structure	Introduces glycosylation near UDP-donor substrate binding site
Related Entries   A list of related LH/PLOD variants found matching the structural position of the mutation currently visualized	SiMPLOD3-358: LH3 ASN223ASN (SNP) SiMPLOD3-359: LH3 ASN223LYS (SNP) SiMPLOD3-385: LH3 ASN223HIS (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)