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UniProtKB/Swiss-Prot Q15910: Variant p.Tyr641Phe

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

Variant position:  641
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LB/B
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 Tyrosine (Y) to Phenylalanine (F) at position 641 (Y641F, p.Tyr641Phe).
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:  Similar physico-chemical property. Both residues are large size and aromatic.
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:  Found in a patient with follicular lymphoma; also in diffuse large B-cell lymphoma; somatic mutation; changed substrate preferences; prefers substrates with greater methylation H3K27me0
Any additional useful information about the variant.

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



Sequence information

Variant position:  641
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:   VAGWGIFIKDPVQKNEFISE  Y CGEIISQDEADRRGKVYDKY
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                         VAGWGIFIKDPVQKNEFISEYCGEIISQDEADRRGKVYDKY

Mouse                         VAGWGIFIKDPVQKNEFISEYCGEIISQDEADRRGKVYDKY

Xenopus tropicalis            VAGWGIFIKDPVQKNEFISEYCGEIISQDEADRRGKVYDKY

Zebrafish                     VAGWGIFIKEPVQKNEFISEYCGEIISQDEADRRGKVYDKY

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
Cross 634 – 634 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)


Literature citations

Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin.
Morin R.D.; Johnson N.A.; Severson T.M.; Mungall A.J.; An J.; Goya R.; Paul J.E.; Boyle M.; Woolcock B.W.; Kuchenbauer F.; Yap D.; Humphries R.K.; Griffith O.L.; Shah S.; Zhu H.; Kimbara M.; Shashkin P.; Charlot J.F.; Tcherpakov M.; Corbett R.; Tam A.; Varhol R.; Smailus D.; Moksa M.; Zhao Y.; Delaney A.; Qian H.; Birol I.; Schein J.; Moore R.; Holt R.; Horsman D.E.; Connors J.M.; Jones S.; Aparicio S.; Hirst M.; Gascoyne R.D.; Marra M.A.;
Nat. Genet. 42:181-185(2010)
Cited for: VARIANTS PHE-641; SER-641; ASN-641; HIS-641 AND CYS-641;

Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation.
Yap D.B.; Chu J.; Berg T.; Schapira M.; Cheng S.W.; Moradian A.; Morin R.D.; Mungall A.J.; Meissner B.; Boyle M.; Marquez V.E.; Marra M.A.; Gascoyne R.D.; Humphries R.K.; Arrowsmith C.H.; Morin G.B.; Aparicio S.A.;
Blood 117:2451-2459(2011)
Cited for: CHARACTERIZATION OF VARIANTS PHE-641 AND ASN-641;

Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27).
McCabe M.T.; Graves A.P.; Ganji G.; Diaz E.; Halsey W.S.; Jiang Y.; Smitheman K.N.; Ott H.M.; Pappalardi M.B.; Allen K.E.; Chen S.B.; Della Pietra A. III; Dul E.; Hughes A.M.; Gilbert S.A.; Thrall S.H.; Tummino P.J.; Kruger R.G.; Brandt M.; Schwartz B.; Creasy C.L.;
Proc. Natl. Acad. Sci. U.S.A. 109:2989-2994(2012)
Cited for: VARIANT GLY-677; CHARACTERIZATION OF VARIANTS ASN-641; CYS-641; HIS-641; PHE-641 AND GLY-677; FUNCTION; CATALYTIC ACTIVITY;

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.