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UniProtKB/Swiss-Prot P02452: Variant p.Gly728Arg

Collagen alpha-1(I) chain
Gene: COL1A1
Chromosomal location: 17q21.3-q22
Variant information

Variant position:  728
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 Glycine (G) to Arginine (R) at position 728 (G728R, p.Gly728Arg).
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 glycine (G) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  Osteogenesis imperfecta 2 (OI2) [MIM:166210]: An autosomal dominant form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI2 is characterized by bone fragility, with many perinatal fractures, severe bowing of long bones, undermineralization, and death in the perinatal period due to respiratory insufficiency. {ECO:0000269|PubMed:10627137, ECO:0000269|PubMed:1460047, ECO:0000269|PubMed:1511982, ECO:0000269|PubMed:1613761, ECO:0000269|PubMed:16566045, ECO:0000269|PubMed:16786509, ECO:0000269|PubMed:18670065, ECO:0000269|PubMed:1874719, ECO:0000269|PubMed:18996919, ECO:0000269|PubMed:1939261, ECO:0000269|PubMed:1953667, ECO:0000269|PubMed:2035536, ECO:0000269|PubMed:2036375, ECO:0000269|PubMed:2037280, ECO:0000269|PubMed:2116413, ECO:0000269|PubMed:2211725, ECO:0000269|PubMed:2339700, ECO:0000269|PubMed:2470760, ECO:0000269|PubMed:25958000, ECO:0000269|PubMed:2777764, ECO:0000269|PubMed:2794057, ECO:0000269|PubMed:2913053, ECO:0000269|PubMed:3016737, ECO:0000269|PubMed:3108247, ECO:0000269|PubMed:3403550, ECO:0000269|PubMed:3667599, ECO:0000269|PubMed:7520724, ECO:0000269|PubMed:7679635, ECO:0000269|PubMed:7691343, ECO:0000269|PubMed:7961597, ECO:0000269|PubMed:8100209, ECO:0000269|PubMed:8349697, ECO:0000269|PubMed:8349698, ECO:0000269|PubMed:8364588, ECO:0000269|PubMed:8456808, ECO:0000269|PubMed:8786074, ECO:0000269|PubMed:9143923, ECO:0000269|Ref.49, ECO:0000269|Ref.52}. 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 OI2.
Any additional useful information about the variant.



Sequence information

Variant position:  728
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1464
The length of the canonical sequence.

Location on the sequence:   AKGDAGAPGAPGSQGAPGLQ  G MPGERGAAGLPGPKGDRGDA
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                         AKGDAGAPGAPGSQGAPGLQGMPGERGAAGLPGPKGDRGDA

                              AKGDAGAPGAPGSQGAPGLQGMPGERGAAGLPGPKGDRGDA

Mouse                         AKGDTGAPGAPGSQGAPGLQGMPGERGAAGLPGPKGDRGDA

Rat                           AKGDTGAPGAPGSQGAPGLQGMPGERGAAGLPGPKGDRGDA

Bovine                        AKGDAGAPGAPGSQGAPGLQGMPGERGAAGLPGPKGDRGDA

Chicken                       AKGDAGAPGAPGNEGPPGLEGMPGERGAAGLPGAKGDRGDP

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 162 – 1218 Collagen alpha-1(I) chain
Region 179 – 1192 Triple-helical region
Modified residue 715 – 715 4-hydroxyproline
Modified residue 718 – 718 4-hydroxyproline
Modified residue 724 – 724 4-hydroxyproline
Modified residue 730 – 730 4-hydroxyproline
Modified residue 739 – 739 4-hydroxyproline


Literature citations

Variable expression of osteogenesis imperfecta in a nuclear family is explained by somatic mosaicism for a lethal point mutation in the alpha 1(I) gene (COL1A1) of type I collagen in a parent.
Wallis G.A.; Starman B.J.; Zinn A.B.; Byers P.H.;
Am. J. Hum. Genet. 46:1034-1040(1990)
Cited for: NUCLEOTIDE SEQUENCE OF 710-745; VARIANT OI2 ARG-728;

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.