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UniProtKB/Swiss-Prot O75398: Variant p.Arg224Trp

Deformed epidermal autoregulatory factor 1 homolog
Gene: DEAF1
Variant information

Variant position:  224
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 224 (R224W, p.Arg224Trp).
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:  Mental retardation, autosomal dominant 24 (MRD24) [MIM:615828]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:21076407, ECO:0000269|PubMed:24726472}. 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 MRD24; loss of DEAF1-promoter repression; loss of transcriptional activation of EIF4G3; loss of DNA binding; decreased interaction with XRCC6.
Any additional useful information about the variant.

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



Sequence information

Variant position:  224
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  565
The length of the canonical sequence.

Location on the sequence:   PVRCRNISGTLYKNRLGSGG  R GRCIKQGENWYSPTEFEAMA
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                         PVRCRNISGTLYKNRLGSGGRGRCIKQGENWYSPTEFEAMA

Chimpanzee                    PVRCRNISGTLYKNRLGSGGRGRCIKQGENWYSPTEFEAMA

Mouse                         PVRCRNISGTLYKSRLGSGGRGRCIKQGENWYSPTEFEAMA

Rat                           PVRCRNISGTLYKSRLGSGGRGRCIKQGENWYSPTEFEAMA

Drosophila                    QIRCKTTCAELYRSKLGSGGRGRCVKYKDKWHTPSEFEHVC

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 – 565 Deformed epidermal autoregulatory factor 1 homolog
Domain 193 – 273 SAND
Alternative sequence 223 – 333 GRGRCIKQGENWYSPTEFEAMAGRASSKDWKRSIRYAGRPLQCLIQDGILNPHAASCTCAACCDDMTLSGPVRLFVPYKRRKKENELPTTPVKKDSPKNITLLPATAATTF -> WDLKPSRCLLHLCCLLRRHDLI. In isoform 4.
Mutagenesis 215 – 215 Y -> Q. Reduces transcription activation.
Mutagenesis 226 – 226 R -> A. Reduces transcription activation.


Literature citations

Mutations affecting the SAND domain of DEAF1 cause intellectual disability with severe speech impairment and behavioral problems.
Vulto-van Silfhout A.T.; Rajamanickam S.; Jensik P.J.; Vergult S.; de Rocker N.; Newhall K.J.; Raghavan R.; Reardon S.N.; Jarrett K.; McIntyre T.; Bulinski J.; Ownby S.L.; Huggenvik J.I.; McKnight G.S.; Rose G.M.; Cai X.; Willaert A.; Zweier C.; Endele S.; de Ligt J.; van Bon B.W.; Lugtenberg D.; de Vries P.F.; Veltman J.A.; van Bokhoven H.; Brunner H.G.; Rauch A.; de Brouwer A.P.; Carvill G.L.; Hoischen A.; Mefford H.C.; Eichler E.E.; Vissers L.E.; Menten B.; Collard M.W.; de Vries B.B.;
Am. J. Hum. Genet. 94:649-661(2014)
Cited for: FUNCTION; INTERACTION WITH XRCC6; DNA-BINDING; TISSUE SPECIFICITY; INVOLVEMENT IN MRD24; VARIANTS MRD24 TRP-224; SER-228; SER-254 AND PRO-264; CHARACTERIZATION OF VARIANTS MRD24 TRP-224; SER-228; SER-254 AND PRO-264; MUTAGENESIS OF LYS-250 AND LYS-253;

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.