UniProtKB/Swiss-Prot P46100: Variant p.Arg246Cys

Transcriptional regulator ATRX
Gene: ATRX
Chromosomal location: Xq13.1-q21.1
Variant information

Variant position:  246
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Arginine (R) to Cysteine (C) at position 246 (R246C, p.Arg246Cys).
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 medium size and polar (C)
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 ATRX; impairs interaction with histone H3 peptides trimethylated at 'Lys-10' (H3K9me3) and reduces localization to pericentromeric heterochromatin foci.
Any additional useful information about the variant.



Sequence information

Variant position:  246
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2492
The length of the canonical sequence.

Location on the sequence:   GGNLICCDFCHNAFCKKCIL  R NLGRKELSTIMDENNQWYCY
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                         GGNLICCDFCHNAFCKKCILRNLGRKELSTIMDENNQWYCY

Chimpanzee                    GGNLICCDFCHNAFCKKCILRNLGRKELSTIMDENNQWYCY

Mouse                         GGNLICCDFCHNAFCKKCILRNLGRKELSTIMDENNQWYCY

Caenorhabditis elegans        -----------------------------------------

Drosophila                    -----------------------------------------

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 – 2492 Transcriptional regulator ATRX
Domain 159 – 296 ADD
Zinc finger 217 – 272 PHD-type; atypical
Mutagenesis 252 – 252 E -> L. Impairs interaction with histone H3 peptides and reduces localization to pericentromeric heterochromatin foci.
Helix 241 – 247


Literature citations

The ATRX-ADD domain binds to H3 tail peptides and reads the combined methylation state of K4 and K9.
Dhayalan A.; Tamas R.; Bock I.; Tattermusch A.; Dimitrova E.; Kudithipudi S.; Ragozin S.; Jeltsch A.;
Hum. Mol. Genet. 20:2195-2203(2011)
Cited for: INTERACTION WITH TRIMETHYLATED HISTONE H3 'LYS-9'; CHARACTERIZATION OF VARIANTS ATRX CYS-246; LEU-246 AND ASP-249; MUTAGENESIS OF TYR-203; TYR-204; ILE-209; ASP-214 AND ASP-217;

ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome.
Iwase S.; Xiang B.; Ghosh S.; Ren T.; Lewis P.W.; Cochrane J.C.; Allis C.D.; Picketts D.J.; Patel D.J.; Li H.; Shi Y.;
Nat. Struct. Mol. Biol. 18:769-776(2011)
Cited for: X-RAY CRYSTALLOGRAPHY (0.93 ANGSTROMS) OF 167-289 IN COMPLEX WITH HISTONE H3K9ME3 PEPTIDE; SUBCELLULAR LOCATION; CHARACTERIZATION OF ATRX VARIANTS ALA-190; PRO-219 AND CYS-246; MUTAGENESIS OF HIS-189; TYR-203; TYR-204; ASP-217; GLU-252 AND LYS-1600;

Molecular genetic study of Japanese patients with X-linked alpha-thalassemia/mental retardation syndrome (ATR-X).
Wada T.; Kubota T.; Fukushima Y.; Saitoh S.;
Am. J. Med. Genet. 94:242-248(2000)
Cited for: VARIANTS ATRX SER-179; LEU-190; ILE-194; CYS-246; PHE-1552; SER-1645 AND CYS-1847;

ATRX syndrome in a girl with a heterozygous mutation in the ATRX Zn finger domain and a totally skewed X-inactivation pattern.
Badens C.; Martini N.; Courrier S.; DesPortes V.; Touraine R.; Levy N.; Edery P.;
Am. J. Med. Genet. A 140:2212-2215(2006)
Cited for: VARIANT ATRX CYS-246;

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.