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UniProtKB/Swiss-Prot O60568: Variant p.Asn223Ser

Multifunctional procollagen lysine hydroxylase and glycosyltransferase LH3
Gene: PLOD3
Chromosomal location: 7q36
Variant information

Variant position:  223
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Asparagine (N) to Serine (S) at position 223 (N223S, p.Asn223Ser).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and polar (N) to small size and polar (S)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in disease:  Lysyl hydroxylase 3 deficiency (LH3 deficiency) [MIM:612394]: Connective tissue disorder. The syndrome is characterized by congenital malformations severely affecting many tissues and organs and revealing features of several collagen disorders, most of them involving COL2A1 (type II collagen). The findings suggest that the failure of lysyl hydroxylation and hydroxylysyl carbohydrate addition, which affects many collagens, is the molecular basis of this syndrome. {ECO:0000269|PubMed:18834968, ECO:0000269|PubMed:30089812}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In LH3 deficiency; generates a new glycosylation site; decreases protein stability; strongly decreases lysyl hydroxylase activity and nearly abolishes glycosyltransferase activity.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  223
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  738
The length of the canonical sequence.

Location on the sequence:   GLREKLSLNLDHKSRIFQNL  N GALDEVVLKFDRNRVRIRNV
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         GLREKLSLNLDHKSRIFQNLNGALDEVVLKFDRNRVRIRNV

Mouse                         GLREKLKLSLDHKSRIFQNLNGALDEVILKFDQNRVRIRNV

Rat                           GLREKLKLSLDHKSRIFQNLNGALDEVVLKFDQNRVRIRNV

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 25 – 738 Multifunctional procollagen lysine hydroxylase and glycosyltransferase LH3
Region 25 – 290 Required for glycosyltransferase activity
Mutagenesis 208 – 208 L -> I. Reduced glucosyltransferase activity.


Literature citations

Molecular architecture of the multifunctional collagen lysyl hydroxylase and glycosyltransferase LH3.
Scietti L.; Chiapparino A.; De Giorgi F.; Fumagalli M.; Khoriauli L.; Nergadze S.; Basu S.; Olieric V.; Cucca L.; Banushi B.; Profumo A.; Giulotto E.; Gissen P.; Forneris F.;
Nat. Commun. 9:3163-3163(2018)
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 25-738 IN COMPLEX WITH IRON; 2-OXOGLUTARATE; MANGANESE AND UDP-GLUCOSE; CATALYTIC ACTIVITY; FUNCTION; COFACTOR; SUBUNIT; DOMAIN; GLYCOSYLATION AT ASN-63 AND ASN-548; DISULFIDE BONDS; CHARACTERIZATION OF VARIANT LH3 DEFICIENCY SER-223; MUTAGENESIS OF TRP-75; TYR-114; THR-672; ARG-714 AND LEU-715;

A connective tissue disorder caused by mutations of the lysyl hydroxylase 3 gene.
Salo A.M.; Cox H.; Farndon P.; Moss C.; Grindulis H.; Risteli M.; Robins S.P.; Myllylae R.;
Am. J. Hum. Genet. 83:495-503(2008)
Cited for: VARIANT LH3 DEFICIENCY SER-223; CHARACTERIZATION OF VARIANT LH3 DEFICIENCY SER-223; CATALYTIC ACTIVITY; FUNCTION;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.