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UniProtKB/Swiss-Prot P43080: Variant p.Asp100Glu

Guanylyl cyclase-activating protein 1
Gene: GUCA1A
Variant information

Variant position:  100
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 Aspartate (D) to Glutamate (E) at position 100 (D100E, p.Asp100Glu).
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:  Similar physico-chemical property. Both residues are medium size and acidic.
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; exhibits an about 28-fold shift of ionic calcium concentration at which the guanylate cyclase activity is halfmaximal.
Any additional useful information about the variant.



Sequence information

Variant position:  100
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:   LSLVLKGKVEQKLRWYFKLY  D VDGNGCIDRDELLTIIQAIR
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                         LSLVLKGKVEQKLRWYFKLYDVDGNGCIDRDELLTIIQAIR

Mouse                         LSLVLKGKVEQKLRWYFKLYDVDGNGCIDRDELLTIIRAIR

Bovine                        LSLVLKGKVEQKLRWYFKLYDVDGNGCIDRDELLTIIRAIR

Chicken                       LSLVLKGKVDQKLRWYFKLYDVDGNGCIDRGELLNIIKAIR

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 87 – 122 EF-hand 3
Calcium binding 100 – 111 2


Literature citations

Mutations in the GUCA1A gene involved in hereditary cone dystrophies impair calcium-mediated regulation of guanylate cyclase.
Kitiratschky V.B.D.; Behnen P.; Kellner U.; Heckenlively J.R.; Zrenner E.; Jaegle H.; Kohl S.; Wissinger B.; Koch K.-W.;
Hum. Mutat. 30:E782-E796(2009)
Cited for: VARIANTS COD3 LYS-89; GLU-100; PHE-151 AND VAL-159; CHARACTERIZATION OF VARIANTS COD3 LYS-89; GLU-100 AND VAL-159; FUNCTION;

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.