UniProtKB/Swiss-Prot Q13873: Variant p.Asp485Gly

Bone morphogenetic protein receptor type-2
Gene: BMPR2
Chromosomal location: 2q33-q34
Variant information

Variant position:  485
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Aspartate (D) to Glycine (G) at position 485 (D485G, p.Asp485Gly).
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 acidic (D) to glycine (G)
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:  Pulmonary hypertension, primary, 1 (PPH1) [MIM:178600]: A rare disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs. {ECO:0000269|PubMed:10903931, ECO:0000269|PubMed:10973254, ECO:0000269|PubMed:11015450, ECO:0000269|PubMed:11115378, ECO:0000269|PubMed:12358323, ECO:0000269|PubMed:15965979, ECO:0000269|PubMed:25187962}. 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 PPH1; complete loss of function.
Any additional useful information about the variant.

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

Sequence information

Variant position:  485
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1038
The length of the canonical sequence.

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.



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.

Chain 27 – 1038 Bone morphogenetic protein receptor type-2
Topological domain 172 – 1038 Cytoplasmic
Domain 203 – 504 Protein kinase

Literature citations

Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension.
Lane K.B.; Machado R.D.; Pauciulo M.W.; Thomson J.R.; Phillips J.A. III; Loyd J.E.; Nichols W.C.; Trembath R.C.; Aldred M.; Brannon C.A.; Conneally P.M.; Foroud T.; Fretwell N.; Gaddipati R.; Koller D.; Loyd E.J.; Morgan N.V.; Newman J.H.; Prince M.A.; Vilarino Gueell C.; Wheeler L.;
Nat. Genet. 26:81-84(2000)
Cited for: VARIANTS PPH1 TRP-118; TYR-347 AND GLY-485;

BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension.
Machado R.D.; Pauciulo M.W.; Thomson J.R.; Lane K.B.; Morgan N.V.; Wheeler L.; Phillips J.A. III; Newman J.H.; Williams D.; Galie N.; Manes A.; McNeil K.; Yacoub M.; Mikhail G.; Rogers P.; Corris P.; Humbert M.; Donnai D.; Martensson G.; Tranebjaerg L.; Loyd J.E.; Trembath R.C.; Nichols W.C.;
Am. J. Hum. Genet. 68:92-102(2001)

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.