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UniProtKB/Swiss-Prot Q8IZQ1: Variant p.Arg2637Trp

WD repeat and FYVE domain-containing protein 3
Gene: WDFY3
Variant information

Variant position:  2637
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  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:  From Arginine (R) to Tryptophan (W) at position 2637 (R2637W, p.Arg2637Trp).
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

Variant description:  In MCPH18; increased cellular DVL3 protein levels as compared to the wild-type protein and loss of attenuation of Wnt signaling; when expressed in Drosophila, causes brain anomalies.
Any additional useful information about the variant.

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



Sequence information

Variant position:  2637
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  3526
The length of the canonical sequence.

Location on the sequence:   VHKRRYLLQPIAVEVFSGDG  R NYLLAFQKGIRNKVYQRFLA
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                         VHKRRYLLQPIAVEVFSGDGRNYLLAFQKGIRNKVYQRFLA

Mouse                         VHKRRYLLQPIAVEVFSGDGRNYLLAFQKGIRNKVYQRFLA

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 1 – 3526 WD repeat and FYVE domain-containing protein 3
Domain 2531 – 2656 BEACH-type PH
Region 2285 – 2981 Sufficient for localization to p62 bodies/ALIS
Region 2586 – 3526 Interaction with SQSTM1


Literature citations

ALFY-controlled DVL3 autophagy regulates Wnt signaling, determining human brain size.
Kadir R.; Harel T.; Markus B.; Perez Y.; Bakhrat A.; Cohen I.; Volodarsky M.; Feintsein-Linial M.; Chervinski E.; Zlotogora J.; Sivan S.; Birnbaum R.Y.; Abdu U.; Shalev S.; Birk O.S.;
PLoS Genet. 12:E1005919-E1005919(2016)
Cited for: VARIANT MCPH18 TRP-2637; CHARACTERIZATION OF VARIANT MCPH18 TRP-2637; FUNCTION;

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.