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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q12805: Variant p.Arg345Trp

EGF-containing fibulin-like extracellular matrix protein 1
Gene: EFEMP1
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Variant information Variant position: help 345 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help 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: help 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: help -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
Variant description: help 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: help Links to websites of interest for the variant.


Sequence information Variant position: help 345 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 493 The length of the canonical sequence.
Location on the sequence: help QVVRSRTCQDINECETTNEC R EDEMCWNYHGGFRCYPRNPC 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         QVVRSRTCQDINECETTNECREDEMCWNYHGGFRCYPRNPC

Mouse                         EVVRSRTCQDINECETTNECREDEMCWNYHGGFRCYPRNPC

Rat                           QVVRSRTCQDINECETTNECREDEMCWNYHGGFRCYPQNPC
Sequence annotation in neighborhood: help 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 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)
Cited for: TISSUE SPECIFICITY; CHARACTERIZATION OF VARIANT DHRD TRP-345; 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)
Cited for: INVOLVEMENT IN DHRD; VARIANT DHRD TRP-345; VARIANT PHE-220; Dominant radial drusen and Arg345Trp EFEMP1 mutation.
Matsumoto M.; Traboulsi E.I.;
Am. J. Ophthalmol. 131:810-812(2001)
Cited for: INVOLVEMENT IN DHRD; 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)
Cited for: CHARACTERIZATION OF VARIANT DHRD TRP-345; EFEMP1 rare variants cause familial juvenile-onset open-angle glaucoma.
Collantes E.R.A.; Delfin M.S.; Fan B.; Torregosa J.M.R.; Siguan-Bell C.; Florcruz N.V.G.; Martinez J.M.D.; Masna-Hidalgo B.J.; Guzman V.P.T.; Anotado-Flores J.F.; Levina F.D.; Hernandez S.R.C.; Collantes A.A.; Sibulo M.C.; Rong S.; Wiggs J.L.;
Hum. Mutat. 43:240-252(2022)
Cited for: VARIANTS GLC1H TYR-80 AND CYS-477; CHARACTERIZATION OF VARIANTS GLC1H TYR-80; TRP-140 AND CYS-477; CHARACTERIZATION OF VARIANT DHRD TRP-345;
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.