UniProtKB/SwissProt variant VAR

Variant information

Variant position:

43

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 Arginine (R) to Tryptophan (W) at position 43 (R43W, p.Arg43Trp).

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

Involvement in disease:

Ventricular septal defect 1 (VSD1) [MIM:614429]: A common form of congenital cardiovascular anomaly that may occur alone or in combination with other cardiac malformations. It can affect any portion of the ventricular septum, resulting in abnormal communications between the two lower chambers of the heart. Classification is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect. Large defects that go unrepaired may give rise to cardiac enlargement, congestive heart failure, pulmonary hypertension, Eisenmenger's syndrome, delayed fetal brain development, arrhythmias, and even sudden cardiac death. {ECO:0000269|PubMed:18672102, ECO:0000269|PubMed:21110066, ECO:0000269|PubMed:21637914, ECO:0000269|PubMed:22101736}. 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 VSD1; significantly reduced activation of the NPPA promoter with the mutant protein compared to wild-type.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs387906770 [ dbSNP | Ensembl ]

Sequence information

Variant position:

43

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

Protein sequence length:

442

The length of the canonical sequence.

Location on the sequence:

PGAFMHGAGAASSPVYVPTP R VPSSVLGLSYLQGGGAGSAS

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                         PGAFMHGAGAASSPVYVPTPRVPSSVLGLSYLQGGGAGSAS

                              PGAFMHGAGAASSPVYVPTPRVPSSVLGLSYLQGGGGAAAS

Mouse                         PGAFMHSAGAASSPVYVPTPRVPSSVLGLSYLQGGGSAAAA

Rat                           PGAFMHSAGAASSPVYVPTPRVPSSVLGLSYLQGGGSGAAS

Xenopus laevis                TGSFMHSATAATSPVYVPTTRVSSMIHSLPYLQ--------

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	1 – 442	Transcription factor GATA-4

Literature citations

A novel GATA4 loss-of-function mutation associated with congenital ventricular septal defect.
Yang Y.Q.; Li L.; Wang J.; Liu X.Y.; Chen X.Z.; Zhang W.; Wang X.Z.; Jiang J.Q.; Liu X.; Fang W.Y.;
Pediatr. Cardiol. 33:539-546(2012)
Cited for: VARIANT VSD1 TRP-43; CHARACTERIZATION OF VARIANT VSD1 TRP-43;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P43694: Variant p.Arg43Trp