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UniProtKB/Swiss-Prot P07320: Variant p.Pro24Thr

Gamma-crystallin D
Variant information

Variant position:  24
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 Proline (P) to Threonine (T) at position 24 (P24T, p.Pro24Thr).
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 medium size and hydrophobic (P) to medium size and polar (T)
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:  Cataract 4, multiple types (CTRCT4) [MIM:115700]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT4 includes crystalline aculeiform, congenital cerulean and non-nuclear polymorphic cataracts, among others. Crystalline aculeiform cataract is characterized by fiberglass-like or needle-like crystals projecting in different directions, through or close to the axial region of the lens. Non-nuclear polymorphic cataract is a partial opacity with variable location between the fetal nucleus of the lens and the equator. The fetal nucleus is normal. The opacities are irregular and look similar to a bunch of grapes and may be present simultaneously in different lens layers. Congenital cerulean cataract is characterized by peripheral bluish and white opacifications organized in concentric layers with occasional central lesions arranged radially. The opacities are observed in the superficial layers of the fetal nucleus as well as the adult nucleus of the lens. Involvement is usually bilateral. Visual acuity is only mildly reduced in childhood. In adulthood, the opacifications may progress, making lens extraction necessary. Histologically the lesions are described as fusiform cavities between lens fibers which contain a deeply staining granular material. Although the lesions may take on various colors, a dull blue is the most common appearance and is responsible for the designation cerulean cataract. {ECO:0000269|PubMed:10521291, ECO:0000269|PubMed:10688888, ECO:0000269|PubMed:10915766, ECO:0000269|PubMed:11371638, ECO:0000269|PubMed:12011157, ECO:0000269|PubMed:12676897, ECO:0000269|PubMed:15709761, ECO:0000269|PubMed:16943771, ECO:0000269|PubMed:17564961, ECO:0000269|PubMed:21031598, ECO:0000269|PubMed:9927684}. 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 CTRCT4; lowered solubility.
Any additional useful information about the variant.

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

Sequence information

Variant position:  24
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  174
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 – 174 Gamma-crystallin D
Domain 2 – 40 Beta/gamma crystallin 'Greek key' 1
Mutagenesis 24 – 25 PN -> TK. Wild-type solubility.
Mutagenesis 24 – 24 P -> TP. Wild-type solubility.
Mutagenesis 24 – 24 P -> V. Slightly lowered solubility.

Literature citations

Decrease in protein solubility and cataract formation caused by the Pro23 to Thr mutation in human gamma D-crystallin.
Pande A.; Annunziata O.; Asherie N.; Ogun O.; Benedek G.B.; Pande J.;
Biochemistry 44:2491-2500(2005)

Novel mutations in the gamma-crystallin genes cause autosomal dominant congenital cataracts.
Santhiya S.T.; Shyam Manohar M.; Rawlley D.; Vijayalakshmi P.; Namperumalsamy P.; Gopinath P.M.; Loester J.; Graw J.;
J. Med. Genet. 39:352-358(2002)

Gamma-D crystallin gene (CRYGD) mutation causes autosomal dominant congenital cerulean cataracts.
Nandrot E.; Slingsby C.; Basak A.; Cherif-Chefchaouni M.; Benazzouz B.; Hajaji Y.; Boutayeb S.; Gribouval O.; Arbogast L.; Berraho A.; Abitbol M.; Hilal L.;
J. Med. Genet. 40:262-267(2003)
Cited for: VARIANT CTRCT4 THR-24;

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.