UniProtKB/Swiss-Prot Q15582: Variant p.Arg555Trp

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

Variant position:  555
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 Arginine (R) to Tryptophan (W) at position 555 (R555W, p.Arg555Trp).
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 basic (R) to large size and aromatic (W)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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, Groenouw type 1 (CDGG1) [MIM:121900]: A rare form of stromal corneal dystrophy characterized by multiple small deposits in the superficial central corneal stroma, and progressive visual impairment. 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 CDGG1; common mutation in Europe and United States; rare in Japan.
Any additional useful information about the variant.



Sequence information

Variant position:  555
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:   GVYTVFAPTNEAFRALPPRE  R SRLLGDAKELANILKYHIGD
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                         GVYTVFAPTNEAFRALPPRERSRLLGDAKELANILKYHIGD

Mouse                         GVYTVFAPTNEAFQAMPPEELNKLLANAKELTNILKYHIGD

Pig                           GVYTVFAPTNEAFQALPLGERNKLLGNAKELANILKYHVGD

Rabbit                        GAYTVFAPTNEAFQALPPGELNKLLGNAKELADILKYHVGE

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 545 – 545 4-carboxyglutamate
Modified residue 554 – 554 4-carboxyglutamate
Modified residue 564 – 564 4-carboxyglutamate
Helix 552 – 559


Literature citations

Kerato-epithelin mutations in four 5q31-linked corneal dystrophies.
Munier F.L.; Korvatska E.; Djemai A.; le Paslier D.; Zografos L.; Pescia G.; Schorderet D.F.;
Nat. Genet. 15:247-251(1997)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS CORNEAL DYSTROPHIES CYS-124; HIS-124; GLN-555 AND TRP-555;

Mutation hot spots in 5q31-linked corneal dystrophies.
Korvatska E.; Munier F.L.; Djemai A.; Wang M.X.; Frueh B.; Chiou A.G.-Y.; Uffer S.; Ballestrazzi E.; Braunstein R.E.; Forster R.K.; Culbertson W.W.; Boman H.; Zografos L.; Schorderet D.F.;
Am. J. Hum. Genet. 62:320-324(1998)
Cited for: VARIANTS CORNEAL DYSTROPHIES CYS-124; HIS-124; GLN-555 AND TRP-555;

Heterogeneity in granular corneal dystrophy: identification of three causative mutations in the TGFBI (BIGH3) gene-lessons for corneal amyloidogenesis.
Stewart H.S.; Ridgway A.E.; Dixon M.J.; Bonshek R.E.; Parveen R.; Black G.C.;
Hum. Mutat. 14:126-132(1999)
Cited for: VARIANTS CORNEAL DYSTROPHIES HIS-124; SER-124 AND TRP-555;

Association of autosomal dominantly inherited corneal dystrophies with BIGH3 gene mutations in Japan.
Mashima Y.; Yamamoto S.; Inoue Y.; Yamada M.; Konishi M.; Watanabe H.; Maeda N.; Shimomura Y.; Kinoshita S.;
Am. J. Ophthalmol. 130:516-517(2000)
Cited for: VARIANTS CORNEAL DYSTROPHIES CYS-124; HIS-124; LEU-124; THR-501; ARG-527; SER-544; GLN-555 AND TRP-555;

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;

BIGH3 mutation spectrum in corneal dystrophies.
Munier F.L.; Frueh B.E.; Othenin-Girard P.; Uffer S.; Cousin P.; Wang M.X.; Heon E.; Black G.C.M.; Blasi M.A.; Balestrazzi E.; Lorenz B.; Escoto R.; Barraquer R.; Hoeltzenbein M.; Gloor B.; Fossarello M.; Singh A.D.; Arsenijevic Y.; Zografos L.; Schorderet D.F.;
Invest. Ophthalmol. Vis. Sci. 43:949-954(2002)
Cited for: VARIANTS CORNEAL DYSTROPHIES CYS-124; HIS-124; SER-124; ARG-518; ARG-538; PHE-540 DEL; TRP-555; LYS-622; ASP-623; ARG-626; PRO-626 AND ASP-631;

TGFBI gene mutations causing lattice and granular corneal dystrophies in Indian patients.
Chakravarthi S.V.V.K.; Kannabiran C.; Sridhar M.S.; Vemuganti G.K.;
Invest. Ophthalmol. Vis. Sci. 46:121-125(2005)
Cited for: VARIANTS CDL1 CYS-124 AND ARG-626; VARIANT CDRB LEU-124; VARIANT CDGG1 TRP-555; VARIANTS LATTICE CORNEAL DYSTROPHY ASP-539; VAL-594 AND 624-VAL-VAL-625 DEL; VARIANT PHE-269;

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.