SiMPLOD v. 0.6.2 alpha

LH3 CYS691ALAFS

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.
SiMPLOD3-260

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.2071del mutation
PLOD3 NM_001084.4:c.2071del - NCBI RefSeq
NCBI SNP: rs786205872
NCBI ClinVar: 6644

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
Warning: this variant incorporates a premature truncation of the aminoacid sequence at residue 691, 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
Salo et al., 2008 - DOI - PubMed

Notes from publications
  A curated excerpt with information about the mutation from the publications found above
Salo et al. reported of a male sibling stillborn at 28 weeks gestation with one nucleotide deletion c.2071delT. The mutation cause a translational frameshift generating a premature translational stop codon in the sequence (p.Cys691AlafsX9). Clinical features are described. The patient was also characterized by the heterozygous nucleotide transition c.668A/G (Asn223Ser). If expressed, the resulting protein would lack of almost all the b-barrel constituting the lysyl-hydroxylase domain.

Structural Observations
  An evaluation of the possible effects/implications of the mutations on the LH3 molecular structure

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 CYS691ALAFS
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.	SiMPLOD3-260
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.2071del mutation	PLOD3 NM_001084.4:c.2071del - NCBI RefSeq NCBI SNP: rs786205872 NCBI ClinVar: 6644
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	Warning: this variant incorporates a premature truncation of the aminoacid sequence at residue 691, 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	Salo et al., 2008 - DOI - PubMed
Notes from publications A curated excerpt with information about the mutation from the publications found above	Salo et al. reported of a male sibling stillborn at 28 weeks gestation with one nucleotide deletion c.2071delT. The mutation cause a translational frameshift generating a premature translational stop codon in the sequence (p.Cys691AlafsX9). Clinical features are described. The patient was also characterized by the heterozygous nucleotide transition c.668A/G (Asn223Ser). If expressed, the resulting protein would lack of almost all the b-barrel constituting the lysyl-hydroxylase domain.
Structural Observations An evaluation of the possible effects/implications of the mutations on the LH3 molecular structure
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):