UniProtKB/SwissProt variant VAR

Variant information

Variant position:

177

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 Glutamine (Q) at position 177 (R177Q, p.Arg177Gln).

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 medium size and polar (Q)

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:

Aortic aneurysm, familial thoracic 8 (AAT8) [MIM:615436]: A disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. {ECO:0000269|PubMed:23910461}. 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 AAT8; impairs cGMP binding; the mutant protein is constitutively active.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs397515330 [ dbSNP | Ensembl ]

Sequence information

Variant position:

177

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

Protein sequence length:

671

The length of the canonical sequence.

Location on the sequence:

LCTMGPGKVFGELAILYNCT R TATVKTLVNVKLWAIDRQCF

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                         LCTMGPGKVFGELAILYNCTRTATVKTLVN-VKLWAIDRQCF

Mouse                         LCTMGPGKVFGELAILYNCTRTATVKTLVN-VKLWAIDRQC

Bovine                        LCTMGPGKVFGELAILYNCTRTATVKTLVN-VKLWAIDRQC

Rabbit                        LCTMGPGKVFGELAILYNCTRTATVKTLVN-VKLWAIDRQC

Drosophila                    LDKMGAGKAFGELAILYNCTRTASIRVLSEAARVWVLDRRV

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	2 – 671	cGMP-dependent protein kinase 1
Nucleotide binding	177 – 178	cAMP or cGMP 1
Region	103 – 220	cGMP-binding, high affinity
Alternative sequence	16 – 297	Missing. In isoform 3.

Literature citations

Recurrent gain-of-function mutation in PRKG1 causes thoracic aortic aneurysms and acute aortic dissections.
Guo D.C.; Regalado E.; Casteel D.E.; Santos-Cortez R.L.; Gong L.; Kim J.J.; Dyack S.; Horne S.G.; Chang G.; Jondeau G.; Boileau C.; Coselli J.S.; Li Z.; Leal S.M.; Shendure J.; Rieder M.J.; Bamshad M.J.; Nickerson D.A.; Kim C.; Milewicz D.M.;
Am. J. Hum. Genet. 93:398-404(2013)
Cited for: VARIANT AAT8 GLN-177; VARIANTS PHE-474 AND ALA-666; CHARACTERIZATION OF VARIANT AAT8 GLN-177;

UniProtKB/Swiss-Prot Q13976: Variant p.Arg177Gln