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UniProtKB/Swiss-Prot Q15910: Variant p.His689Tyr

Histone-lysine N-methyltransferase EZH2
Gene: EZH2
Variant information

Variant position:  689
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 Histidine (H) to Tyrosine (Y) at position 689 (H689Y, p.His689Tyr).
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 medium size and polar (H) to large size and aromatic (Y)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  2
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 WVS; decreased histone methyltransferase activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  689
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  746
The length of the canonical sequence.

Location on the sequence:   LNNDFVVDATRKGNKIRFAN  H SVNPNCYAKVMMVNGDHRIG
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                         LNNDFVVDATRKGNKIRFANHSVNPNCYAKVMMVNGDHRIG

Mouse                         LNNDFVVDATRKGNKIRFANHSVNPNCYAKVMMVNGDHRIG

Xenopus tropicalis            LNNDFVVDATRKGNKIRFANHSVNPNCYAKVMMVNGDHRIG

Zebrafish                     LNNDFVVDATRKGNKIRFANHSVNPNCYAKVMMVNGDHRIG

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 – 746 Histone-lysine N-methyltransferase EZH2
Domain 612 – 727 SET
Mutagenesis 689 – 689 H -> A. Abrogates methyltransferase activity.
Beta strand 687 – 689


Literature citations

Mutations in EZH2 cause Weaver syndrome.
Gibson W.T.; Hood R.L.; Zhan S.H.; Bulman D.E.; Fejes A.P.; Moore R.; Mungall A.J.; Eydoux P.; Babul-Hirji R.; An J.; Marra M.A.; Chitayat D.; Boycott K.M.; Weaver D.D.; Jones S.J.;
Am. J. Hum. Genet. 90:110-118(2012)
Cited for: VARIANTS WVS SER-132; TYR-153 DEL AND TYR-689;

Weaver Syndrome-Associated EZH2 Protein Variants Show Impaired Histone Methyltransferase Function In Vitro.
Cohen A.S.; Yap D.B.; Lewis M.E.; Chijiwa C.; Ramos-Arroyo M.A.; Tkachenko N.; Milano V.; Fradin M.; McKinnon M.L.; Townsend K.N.; Xu J.; Van Allen M.I.; Ross C.J.; Dobyns W.B.; Weaver D.D.; Gibson W.T.;
Hum. Mutat. 37:301-307(2016)
Cited for: VARIANTS WVS CYS-133 AND CYS-679; CHARACTERIZATION OF VARIANTS WVS SER-132; CYS-133; TYR-153 DEL; CYS-679 AND TYR-689; VARIANT HIS-185; CHARACTERIZATION OF VARIANT HIS-185; MUTAGENESIS OF PHE-667;

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.