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UniProtKB/Swiss-Prot P13497: Variant p.Gly12Arg

Bone morphogenetic protein 1
Gene: BMP1
Chromosomal location: 8p21
Variant information

Variant position:  12
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 12 (G12R, p.Gly12Arg).
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 13 (OI13) [MIM:614856]: An autosomal recessive 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. OI13 is characterized by normal teeth, faint blue sclerae, severe growth deficiency, borderline osteoporosis, severe bone deformity, and recurrent fractures affecting both upper and lower limbs. {ECO:0000269|PubMed:22052668, ECO:0000269|PubMed:22482805, ECO:0000269|PubMed:25402547}. 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 OI13; the mutation leads to severely reduced post-translational N-glycosylation of the protein and impairs protein secretion; leads to both reduced secretion and subsequent reduced processing of the substrates CHRD and COL1A1.
Any additional useful information about the variant.

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



Sequence information

Variant position:  12
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  986
The length of the canonical sequence.

Location on the sequence:   MPGVARLPLLL  G LLLLPRPGRPLDLADYTYDL
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                         MPGVAR-------LPLLLGLLLLPRPGRPLDLADYTYDL

Mouse                         MPGVARPPLPLLSLPLLLLLLLLPRAGRPLDL

Xenopus laevis                --------------------------------

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
Signal peptide 1 – 22


Literature citations

Paired basic/Furin-like proprotein convertase cleavage of Pro-BMP-1 in the trans-Golgi network.
Leighton M.; Kadler K.E.;
J. Biol. Chem. 278:18478-18484(2003)
Cited for: SUBCELLULAR LOCATION; PROTEOLYTIC CLEAVAGE; MUTAGENESIS OF 119-ARG--ARG-120;

Attenuated BMP1 function compromises osteogenesis, leading to bone fragility in humans and zebrafish.
Asharani P.V.; Keupp K.; Semler O.; Wang W.; Li Y.; Thiele H.; Yigit G.; Pohl E.; Becker J.; Frommolt P.; Sonntag C.; Altmuller J.; Zimmermann K.; Greenspan D.S.; Akarsu N.A.; Netzer C.; Schonau E.; Wirth R.; Hammerschmidt M.; Nurnberg P.; Wollnik B.; Carney T.J.;
Am. J. Hum. Genet. 90:661-674(2012)
Cited for: VARIANT OI13 ARG-12; CHARACTERIZATION OF VARIANT OI13 ARG-12; INVOLVEMENT IN OI13;

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.