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UniProtKB/Swiss-Prot Q4FZB7: Variant p.Trp264Ser

Histone-lysine N-methyltransferase KMT5B
Gene: KMT5B
Variant information

Variant position:  264
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
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 Tryptophan (W) to Serine (S) at position 264 (W264S, p.Trp264Ser).
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 aromatic (W) to small size and polar (S)
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 51 (MRD51) [MIM:617788]: A form of mental retardation, 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:28191889, ECO:0000269|PubMed:29276005}. 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 MRD51; unknown pathological significance.
Any additional useful information about the variant.

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



Sequence information

Variant position:  264
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  885
The length of the canonical sequence.

Location on the sequence:   RHGENDFSVMYSTRKNCAQL  W LGPAAFINHDCRPNCKFVST
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                         RHGENDFSVMYSTRKNCAQLWLGPAAFINHDCRPNCKFVST

Mouse                         RHGENDFSVMYSTRKNCAQLWLGPAAFINHDCRPNCKFVST

Rat                           RHGENDFSVMYSTRKNCAQLWLGPAAFINHDCRPNCKFVST

Bovine                        RHGENDFSVMYSTRKNCAQLWLGPAAFINHDCRPNCKFVST

Zebrafish                     RHGENDFSVMYSTRKNCAQLWLGPAAFINHDCRPNCKFVST

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 – 885 Histone-lysine N-methyltransferase KMT5B
Domain 193 – 308 SET
Metal binding 275 – 275 Zinc
Binding site 257 – 257 S-adenosyl-L-methionine
Alternative sequence 274 – 274 D -> DLINS. In isoform 3.
Mutagenesis 251 – 251 S -> A. Abolishes histone methyltransferase activity (H4-K20 specific).
Mutagenesis 264 – 264 W -> A. Abolishes histone methyltransferase activity (H4-K20 specific).
Mutagenesis 281 – 281 F -> A. Abolishes histone methyltransferase activity (H4-K20 specific).
Beta strand 260 – 266


Literature citations

Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.
Stessman H.A.; Xiong B.; Coe B.P.; Wang T.; Hoekzema K.; Fenckova M.; Kvarnung M.; Gerdts J.; Trinh S.; Cosemans N.; Vives L.; Lin J.; Turner T.N.; Santen G.; Ruivenkamp C.; Kriek M.; van Haeringen A.; Aten E.; Friend K.; Liebelt J.; Barnett C.; Haan E.; Shaw M.; Gecz J.; Anderlid B.M.; Nordgren A.; Lindstrand A.; Schwartz C.; Kooy R.F.; Vandeweyer G.; Helsmoortel C.; Romano C.; Alberti A.; Vinci M.; Avola E.; Giusto S.; Courchesne E.; Pramparo T.; Pierce K.; Nalabolu S.; Amaral D.G.; Scheffer I.E.; Delatycki M.B.; Lockhart P.J.; Hormozdiari F.; Harich B.; Castells-Nobau A.; Xia K.; Peeters H.; Nordenskjoeld M.; Schenck A.; Bernier R.A.; Eichler E.E.;
Nat. Genet. 49:515-526(2017)
Cited for: INVOLVEMENT IN MRD51; VARIANTS MRD51 SER-264; VAL-513 AND GLN-540;

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.