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UniProtKB/Swiss-Prot P43080: Variant p.Gly86Arg

Guanylyl cyclase-activating protein 1
Gene: GUCA1A
Variant information

Variant position:  86
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 Glycine (G) to Arginine (R) at position 86 (G86R, p.Gly86Arg).
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 glycine (G) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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 CORD14; results in impaired guanylate cyclase regulator activity; interferes with GCAP1 calcium-dependent transition from activator to inhibitor of GUCY2D; the mutant protein remains active at high calcium concentrations causing persistent GUCY2D stimulation.
Any additional useful information about the variant.



Sequence information

Variant position:  86
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  201
The length of the canonical sequence.

Location on the sequence:   NKDGYIDFMEYVAALSLVLK  G KVEQKLRWYFKLYDVDGNGC
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                         NKDGYIDFMEYVAALSLVLKGKVEQKLRWYFKLYDVDGNGC

Mouse                         NKDGYIDFMEYVAALSLVLKGKVEQKLRWYFKLYDVDGNGC

Bovine                        NKDGYIDFMEYVAALSLVLKGKVEQKLRWYFKLYDVDGNGC

Chicken                       NKDGYIDFMEYVAALSLVLKGKVDQKLRWYFKLYDVDGNGC

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.

TypePositionsDescription
Chain 2 – 201 Guanylyl cyclase-activating protein 1
Domain 51 – 86 EF-hand 2


Literature citations

A G86R mutation in the calcium-sensor protein GCAP1 alters regulation of retinal guanylyl cyclase and causes dominant cone-rod degeneration.
Peshenko I.V.; Cideciyan A.V.; Sumaroka A.; Olshevskaya E.V.; Scholten A.; Abbas S.; Koch K.W.; Jacobson S.G.; Dizhoor A.M.;
J. Biol. Chem. 294:3476-3488(2019)
Cited for: VARIANT CORD14 ARG-86; CHARACTERIZATION OF VARIANT CORD14 ARG-86; FUNCTION;

Constitutive activation of guanylate cyclase by the G86R GCAP1 variant is due to 'locking' cation-pi interactions that impair the activator-to-inhibitor structural transition.
Abbas S.; Marino V.; Bielefeld L.; Koch K.W.; Dell'Orco D.;
Int. J. Mol. Sci. 21:0-0(2020)
Cited for: CHARACTERIZATION OF VARIANT CORD14 ARG-86;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.