UniProtKB/Swiss-Prot Q15582: Variant p.Ala546Thr

Transforming growth factor-beta-induced protein ig-h3
Gene: TGFBI
Chromosomal location: 5q31
Variant information

Variant position:  546
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Alanine (A) to Threonine (T) at position 546 (A546T, p.Ala546Thr).
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 small size and hydrophobic (A) to medium size and polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Corneal dystrophy, lattice type 3A (CDL3A) [MIM:608471]: A form of lattice corneal dystrophy, a class of inherited stromal amyloidoses characterized by pathognomonic branching lattice figures in the cornea. CDL3A is characterized by decreased visual acuity, and the presence of thick, ropy branching lattice lines and accumulations of amyloid deposits in the corneal stroma. Systemic amyloidosis is absent. CDL3A clinically resembles to lattice corneal dystrophy type 3, but differs in that its age of onset is 70 to 90 years. It has an autosomal dominant inheritance pattern. 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 CDL3A.
Any additional useful information about the variant.



Sequence information

Variant position:  546
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  683
The length of the canonical sequence.

Location on the sequence:   GLTETLNREGVYTVFAPTNE  A FRALPPRERSRLLGDAKELA
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                         GLTETLNREGVYTVFAPTNEAFRALPPRERSRLLGDAKELA

Mouse                         GLMEILNREGVYTVFAPTNEAFQAMPPEELNKLLANAKELT

Pig                           GLTETLNREGVYTVFAPTNEAFQALPLGERNKLLGNAKELA

Rabbit                        RLTETLNREGAYTVFAPTNEAFQALPPGELNKLLGNAKELA

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 24 – 683 Transforming growth factor-beta-induced protein ig-h3
Domain 502 – 632 FAS1 4
Modified residue 529 – 529 4-carboxyglutamate
Modified residue 534 – 534 4-carboxyglutamate
Modified residue 545 – 545 4-carboxyglutamate
Modified residue 554 – 554 4-carboxyglutamate
Modified residue 564 – 564 4-carboxyglutamate
Helix 544 – 549


Literature citations

Histologic phenotype-genotype correlation of corneal dystrophies associated with eight distinct mutations in the TGFBI gene.
Dighiero P.; Niel F.; Ellies P.; D'Hermies F.; Savoldelli M.; Renard G.; Delpech M.; Valleix S.;
Ophthalmology 108:818-823(2001)
Cited for: VARIANTS CORNEAL DYSTROPHIES CYS-124; HIS-124; LEU-124; 125-THR-GLU-126 DEL; THR-546; GLN-555; TRP-555 AND ARG-626;

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.