UniProtKB/Swiss-Prot Q12805: Variant p.Arg345Trp

EGF-containing fibulin-like extracellular matrix protein 1
Gene: EFEMP1
Chromosomal location: 2p16
Variant information

Variant position:  345
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 Arginine (R) to Tryptophan (W) at position 345 (R345W, p.Arg345Trp).
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:  Doyne honeycomb retinal dystrophy (DHRD) [MIM:126600]: Autosomal dominant disease characterized by yellow-white deposits known as drusen that accumulate beneath the retinal pigment epithelium. {ECO:0000269|PubMed:10369267, ECO:0000269|PubMed:11384588, ECO:0000269|PubMed:12242346, ECO:0000269|PubMed:17666404}. 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 DHRD; misfolded, accumulates in cells due to inefficient secretion; induces the formation of deposits between Bruch's membrane and the retinal pigment epithelium where it accumulates.
Any additional useful information about the variant.

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

Sequence information

Variant position:  345
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  493
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 18 – 493 EGF-containing fibulin-like extracellular matrix protein 1
Domain 334 – 378 EGF-like 6; calcium-binding
Region 259 – 493 Mediates interaction with TIMP3
Disulfide bond 338 – 350
Disulfide bond 344 – 359

Literature citations

Aberrant accumulation of EFEMP1 underlies drusen formation in Malattia Leventinese and age-related macular degeneration.
Marmorstein L.Y.; Munier F.L.; Arsenijevic Y.; Schorderet D.F.; McLaughlin P.J.; Chung D.; Traboulsi E.; Marmorstein A.D.;
Proc. Natl. Acad. Sci. U.S.A. 99:13067-13072(2002)

A single EFEMP1 mutation associated with both malattia Leventinese and Doyne honeycomb retinal dystrophy.
Stone E.M.; Lotery A.J.; Munier F.L.; Heon E.; Piguet B.; Guymer R.H.; Vandenburgh K.; Cousin P.; Nishimura D.; Swiderski R.E.; Silvestri G.; Mackey D.A.; Hagerman G.S.; Bird A.C.; Sheffield V.C.; Schorderet D.F.;
Nat. Genet. 22:199-202(1999)

Dominant radial drusen and Arg345Trp EFEMP1 mutation.
Matsumoto M.; Traboulsi E.I.;
Am. J. Ophthalmol. 131:810-812(2001)
Cited for: VARIANT DHRD TRP-345;

The R345W mutation in EFEMP1 is pathogenic and causes AMD-like deposits in mice.
Fu L.; Garland D.; Yang Z.; Shukla D.; Rajendran A.; Pearson E.; Stone E.M.; Zhang K.; Pierce E.A.;
Hum. Mol. Genet. 16:2411-2422(2007)

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.