UniProtKB/SwissProt variant VAR

Variant information

Variant position:

374

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

Type of variant:

LP/P [Disclaimer]

The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Arginine (R) to Tryptophan (W) at position 374 (R374W, p.Arg374Trp).

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 large size and basic (R) to large size and aromatic (W)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-3

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

Variant description:

In HHT2.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs28936401 [ dbSNP | Ensembl ]

Sequence information

Variant position:

374

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:

MHSQGSDYLDIGNNPRVGTK R YMAPEVLDEQIRTDCFESYK

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                         MHSQGSDYLDIGNNPRVGTKRYMAPEVLDEQIRTDCFESYK

Mouse                         MHSQSSDYLDIGNNPRVGTKRYMAPEVLDEHIRTDCFESYK

Rat                           MHSQSSDYLDIGNNPRVGTKRYMAPEVLDEQIRTDCFESYK

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	373 – 375

Literature citations

The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2.
Berg J.N.; Gallione C.J.; Stenzel T.T.; Johnson D.W.; Allen W.P.; Schwartz C.E.; Jackson C.E.; Porteous M.E.M.; Marchuk D.A.;
Am. J. Hum. Genet. 61:60-67(1997)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS HHT2 CYS-50; GLN-67; ILE-333; TRP-374 AND THR-424;

Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families.
Kjeldsen A.D.; Brusgaard K.; Poulsen L.; Kruse T.; Rasmussen K.; Green A.; Vase P.;
Am. J. Med. Genet. 98:298-302(2001)
Cited for: VARIANTS HHT2 TRP-374 AND ASN-398;

Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia.
Harrison R.E.; Flanagan J.A.; Sankelo M.; Abdalla S.A.; Rowell J.; Machado R.D.; Elliott C.G.; Robbins I.M.; Olschewski H.; McLaughlin V.; Gruenig E.; Kermeen F.; Halme M.; Raeisaenen-Sokolowski A.; Laitinen T.; Morrell N.W.; Trembath R.C.;
J. Med. Genet. 40:865-871(2003)
Cited for: VARIANTS HHT2 ALA-179; ASP-211; TYR-344; TRP-374; GLN-374; SER-399; GLN-411 AND THR-487; CHARACTERIZATION OF VARIANTS HHT2 CYS-50; GLN-67; TRP-77; ALA-179; ASP-211; SER-232 DEL; ASP-254 DEL; ILE-333; TYR-344; GLN-374; LEU-378; GLN-411 AND THR-487;

Hepatic manifestation is associated with ALK1 in hereditary hemorrhagic telangiectasia: identification of five novel ALK1 and one novel ENG mutations.
Kuehl H.K.A.; Caselitz M.; Hasenkamp S.; Wagner S.; El-Harith E.-H.A.; Manns M.P.; Stuhrmann M.;
Hum. Mutat. 25:320-320(2005)
Cited for: VARIANTS HHT2 TRP-67; TRP-374; LYS-379; ASP-407; TRP-411; VAL-425 AND PHE-425 DEL;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P37023: Variant p.Arg374Trp