UniProtKB/SwissProt variant VAR

Variant information

Variant position:

863

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 Serine (S) to Asparagine (N) at position 863 (S863N, p.Ser863Asn).

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 small size and polar (S) to medium size and polar (N)

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:24936649, ECO:0000269|PubMed:25187962, ECO:0000269|PubMed:28507310}. 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; abnormal subcellular localization; significant increase in apoptosis of endothelial cells; significant decrease in proliferation of endothelial cells; significant decrease in nitric oxide synthesis by endothelial cells; significant increase in endothelin 1 synthesis by endothelial cells.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs1006246556 [ dbSNP | Ensembl ]

Sequence information

Variant position:

863

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

Protein sequence length:

1038

The length of the canonical sequence.

Location on the sequence:

AQEMLQNQFIGEDTRLNINS S PDEHEPLLRREQQAGHDEGV

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                         AQEMLQNQFIGEDTRLNINSSPDEHEPLLRREQQAGHDEGV

Mouse                         SQEMLQNQFIGEDTRLNINSSPDEHEPLLRREQQAGHDEGV

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.

Type	Positions	Description
Chain	27 – 1038	Bone morphogenetic protein receptor type-2
Topological domain	172 – 1038	Cytoplasmic
Alternative sequence	531 – 1038	Missing. In isoform 2.

Literature citations

Functional changes in pulmonary arterial endothelial cells associated with BMPR2 mutations.
Wang H.; Ji R.; Meng J.; Cui Q.; Zou W.; Li L.; Wang G.; Sun L.; Li Z.; Huo L.; Fan Y.; Penny D.J.;
PLoS ONE 9:E106703-E106703(2014)
Cited for: VARIANTS PPH1 CYS-67 AND ASN-863; CHARACTERIZATION OF VARIANTS PPH1 CYS-67 AND ASN-863; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13873: Variant p.Ser863Asn