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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O75398: Variant p.Arg254Ser

Deformed epidermal autoregulatory factor 1 homolog
Gene: DEAF1
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Variant information Variant position: help 254 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 Serine (S) at position 254 (R254S, p.Arg254Ser). 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 small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -1 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 VSVS; loss of DEAF1-promoter repression; gain of transcriptional activation of EIF4G3; a 9-fold reduction in DNA binding. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 254 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 565 The length of the canonical sequence.
Location on the sequence: help WYSPTEFEAMAGRASSKDWK R SIRYAGRPLQCLIQDGILNP 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                         WYSPTEFEAMAGRASSKDWKRSIRYAGRPLQCLIQDGILNP

Chimpanzee                    WYSPTEFEAMAGRASSKDWKRSIRYAGRPLQCLIQDGILNP

Mouse                         WYSPTEFEAMAGRASSKDWKRSIRYAGRPLQCLIQDGILNP

Rat                           WYSPTEFEAMAGRASSKDWKRSIRYAGRPLQCLIQDGILNP

Drosophila                    WHTPSEFEHVCGRGSSKDWKRSIKYGGKSLQSLIDEGTLTP
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 1 – 565 Deformed epidermal autoregulatory factor 1 homolog
Domain 193 – 273 SAND
Alternative sequence 223 – 333 GRGRCIKQGENWYSPTEFEAMAGRASSKDWKRSIRYAGRPLQCLIQDGILNPHAASCTCAACCDDMTLSGPVRLFVPYKRRKKENELPTTPVKKDSPKNITLLPATAATTF -> WDLKPSRCLLHLCCLLRRHDLI. In isoform 4.
Mutagenesis 246 – 246 R -> A. Reduces transcription activation.
Mutagenesis 250 – 250 K -> A. Abolishes DNA-binding. Loss of DEAF1-promoter repression; when associated with A-253. Loss of transcriptional activation of EIF4G3; when associated with A-253. Loss of interaction with XRCC6; when associated with A-253. Loss of DNA binding; when associated with A-253.
Mutagenesis 252 – 252 W -> Q. Abolishes DNA-binding.
Mutagenesis 253 – 253 K -> A. Abolishes DNA-binding. oss of DEAF1-promoter repression; when associated with A-250. Loss of transcriptional activation of EIF4G3; when associated with A-250. Loss of interaction with XRCC6; when associated with A-250. Loss of DNA binding; when associated with A-250.



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 VSVS; VARIANTS VSVS TRP-224; SER-228; SER-254 AND PRO-264; CHARACTERIZATION OF VARIANTS VSVS 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.