SiMPLOD v. 0.6.2 alpha

LH2a SER166END (LH2a) - SER166END (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.
SiMPLOD2-250

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.497C>G mutation
PLOD2 NM_000935.2:c.497C>G - NCBI RefSeq
NCBI SNP: rs201501322

Mutation type
  Current information about the clinical implications of the mutation
Likely pathogenic

Disease Phenotype
  Annotated information about disease phenotypes associated to this mutation
Moderate Osteogenesis Imperfecta - 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
Warning: this variant incorporates a premature truncation of the aminoacid sequence at residue 166, 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
Leal et al., 2018 - DOI - PubMed

Notes from publications
  A curated excerpt with information about the mutation from the publications found above
Leal et al. described of two sibs with a kyphomelic dysplasia-like phenotype who were stillborn. Both had compound heterozygous variants in PLOD2 (p.Asp585Val and Ser166end). Clinical and familiar features are described. The nonsense variant Ser166End was previously detected in 61/276822 alleles (all heterozygous) in the gnomAD database of which the majority were found in the Finnish population (minor allele frequency of 1/525). This nonsense variant was inherited from the healthy father. The healthy son was a heterozygous carrier of the mutation.

Structural Observations
  An evaluation of the possible effects/implications of the mutations on the LH2a molecular structure

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 SER166END (LH2a) - SER166END (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.	SiMPLOD2-250
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.497C>G mutation	PLOD2 NM_000935.2:c.497C>G - NCBI RefSeq NCBI SNP: rs201501322
Mutation type Current information about the clinical implications of the mutation	Likely pathogenic
Disease Phenotype Annotated information about disease phenotypes associated to this mutation	Moderate Osteogenesis Imperfecta - 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	Warning: this variant incorporates a premature truncation of the aminoacid sequence at residue 166, 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	Leal et al., 2018 - DOI - PubMed
Notes from publications A curated excerpt with information about the mutation from the publications found above	Leal et al. described of two sibs with a kyphomelic dysplasia-like phenotype who were stillborn. Both had compound heterozygous variants in PLOD2 (p.Asp585Val and Ser166end). Clinical and familiar features are described. The nonsense variant Ser166End was previously detected in 61/276822 alleles (all heterozygous) in the gnomAD database of which the majority were found in the Finnish population (minor allele frequency of 1/525). This nonsense variant was inherited from the healthy father. The healthy son was a heterozygous carrier of the mutation.
Structural Observations An evaluation of the possible effects/implications of the mutations on the LH2a molecular structure
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):