Home  |  Contact

UniProtKB/Swiss-Prot P43080: Variant p.Tyr99Cys

Guanylyl cyclase-activating protein 1
Gene: GUCA1A
Variant information

Variant position:  99
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 Tyrosine (Y) to Cysteine (C) at position 99 (Y99C, p.Tyr99Cys).
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 aromatic (Y) to medium size and polar (C)
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

Involvement in disease:  Cone dystrophy 3 (COD3) [MIM:602093]: An autosomal dominant cone dystrophy. Cone dystrophies are retinal dystrophies characterized by progressive degeneration of the cone photoreceptors with preservation of rod function, as indicated by electroretinogram. However, some rod involvement may be present in some cone dystrophies, particularly at late stage. Affected individuals suffer from photophobia, loss of visual acuity, color vision and central visual field. Another sign is the absence of macular lesions for many years. Cone dystrophies are distinguished from the cone-rod dystrophies in which some loss of peripheral vision also occurs. {ECO:0000269|PubMed:11108966, ECO:0000269|PubMed:11146732, ECO:0000269|PubMed:11484154, ECO:0000269|PubMed:15505030, ECO:0000269|PubMed:15735604, ECO:0000269|PubMed:15790869, ECO:0000269|PubMed:19459154, ECO:0000269|PubMed:9425234}. 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 COD3; type 1A; alters calcium ion sensitivity, leading to the constitutive stimulating activity of GC1 at high calcium ion concentration, where normal GUCA1A inhibits it.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.

Sequence information

Variant position:  99
The position of the amino-acid change on the UniProtKB canonical protein sequence.

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

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.





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.

Chain 2 – 201 Guanylyl cyclase-activating protein 1
Domain 87 – 122 EF-hand 3

Literature citations

A mutation in guanylate cyclase activator 1A (GUCA1A) in an autosomal dominant cone dystrophy pedigree mapping to a new locus on chromosome 6p21.1.
Payne A.M.; Downes S.M.; Bessant D.A.R.; Taylor R.; Holder G.E.; Warren M.J.; Bird A.C.; Bhattacharya S.S.;
Hum. Mol. Genet. 7:273-277(1998)
Cited for: VARIANT COD3 CYS-99;

Ca(2+)-binding proteins in the retina: from discovery to etiology of human disease.
Sokal I.; Li N.; Verlinde C.L.M.J.; Haeseleer F.; Baehr W.; Palczewski K.;
Biochim. Biophys. Acta 1498:233-251(2000)

Autosomal dominant cone and cone-rod dystrophy with mutations in the guanylate cyclase activator 1A gene-encoding guanylate cyclase activating protein-1.
Downes S.M.; Holder G.E.; Fitzke F.W.; Payne A.M.; Warren M.J.; Bhattacharya S.S.; Bird A.C.;
Arch. Ophthalmol. 119:96-105(2001)
Cited for: VARIANTS COD3 LEU-50 AND CYS-99;

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.