UniProtKB/SwissProt variant VAR

Variant information

Variant position:

306

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 Alanine (A) to Proline (P) at position 306 (A306P, p.Ala306Pro).

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 hydrophobic (A) to medium size and hydrophobic (P)

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:

Telangiectasia, hereditary hemorrhagic, 2 (HHT2) [MIM:600376]: A multisystemic vascular dysplasia leading to dilation of permanent blood vessels and arteriovenous malformations of skin, mucosa, and viscera. The disease is characterized by recurrent epistaxis and gastro-intestinal hemorrhage. Visceral involvement includes arteriovenous malformations of the lung, liver, and brain. {ECO:0000269|PubMed:10694922, ECO:0000269|PubMed:10767348, ECO:0000269|PubMed:11170071, ECO:0000269|PubMed:11484689, ECO:0000269|PubMed:14684682, ECO:0000269|PubMed:15024723, ECO:0000269|PubMed:15712270, ECO:0000269|PubMed:16525724, ECO:0000269|PubMed:16752392, ECO:0000269|PubMed:20414677, ECO:0000269|PubMed:26176610, ECO:0000269|PubMed:8640225, ECO:0000269|PubMed:9245985}. 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 HHT2; loss of receptor activity in response to BMP9; retained in the endoplasmic reticulum.

Any additional useful information about the variant.

Sequence information

Variant position:

306

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

Protein sequence length:

503

The length of the canonical sequence.

Location on the sequence:

YDFLQRQTLEPHLALRLAVS A ACGLAHLHVEIFGTQGKPAI

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                         YDFLQRQTLEPHLALRLAVSAACGLAHLHVEIFGTQGKPAI

Mouse                         YDFLQRQTLEPQLALRLAVSAACGLAHLHVEIFGTQGKPAI

Rat                           YDFLQRQTLEPQLALRLAVSAACGLAHLHVEIFGTQGKPAI

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	22 – 503	Serine/threonine-protein kinase receptor R3
Topological domain	142 – 503	Cytoplasmic
Domain	202 – 492	Protein kinase
Helix	296 – 314

Literature citations

Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France.
Lesca G.; Plauchu H.; Coulet F.; Lefebvre S.; Plessis G.; Odent S.; Riviere S.; Leheup B.; Goizet C.; Carette M.-F.; Cordier J.-F.; Pinson S.; Soubrier F.; Calender A.; Giraud S.;
Hum. Mutat. 23:289-299(2004)
Cited for: VARIANTS HHT2 ARG-48; LYS-215; ARG-223; ARG-229; SER-233 DEL; PHE-285; PRO-306; TYR-314; PRO-337; PRO-347; GLN-374; VAL-376; LYS-379; GLY-397; TRP-411; PRO-411; GLN-411; LEU-425; LEU-479; VAL-482 AND TRP-484;

Functional and splicing defect analysis of 23 ACVRL1 mutations in a cohort of patients affected by hereditary hemorrhagic telangiectasia.
Alaa El Din F.; Patri S.; Thoreau V.; Rodriguez-Ballesteros M.; Hamade E.; Bailly S.; Gilbert-Dussardier B.; Abou Merhi R.; Kitzis A.;
PLoS ONE 10:E0132111-E0132111(2015)
Cited for: VARIANTS HHT2 GLY-41; TYR-41; GLY-46; PRO-47; TYR-66; PHE-77; ASP-211; SER-211; VAL-245; PRO-306; VAL-313; TYR-314; SER-378; ASP-379; LYS-379; GLY-404; TRP-411; MET-441 AND TYR-443; VARIANTS ASP-111 AND PHE-417; CHARACTERIZATION OF VARIANTS HHT2 GLY-41; TYR-41; GLY-46; PRO-47; TYR-66; PHE-77; ASP-211; SER-211; VAL-245; PRO-306; VAL-313; TYR-314; SER-378; ASP-379; LYS-379; GLY-404; TRP-411; MET-441 AND TYR-443; CHARACTERIZATION OF VARIANTS ASP-111 AND PHE-417; FUNCTION; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P37023: Variant p.Ala306Pro