UniProtKB/Swiss-Prot O14686: Variant p.Arg5340Leu

Histone-lysine N-methyltransferase 2D
Gene: KMT2D
Chromosomal location: 12q12-q13
Variant information

Variant position:  5340
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 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 Arginine (R) to Leucine (L) at position 5340 (R5340L, p.Arg5340Leu).
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 hydrophobic (L)
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

Involvement in disease:  Kabuki syndrome 1 (KABUK1) [MIM:147920]: A congenital mental retardation syndrome with additional features, including postnatal dwarfism, a peculiar facies characterized by long palpebral fissures with eversion of the lateral third of the lower eyelids, a broad and depressed nasal tip, large prominent earlobes, a cleft or high-arched palate, scoliosis, short fifth finger, persistence of fingerpads, radiographic abnormalities of the vertebrae, hands, and hip joints, and recurrent otitis media in infancy. {ECO:0000269|PubMed:20711175, ECO:0000269|PubMed:21280141, ECO:0000269|PubMed:21607748, ECO:0000269|PubMed:21658225, ECO:0000269|PubMed:21671394, ECO:0000269|PubMed:22126750, ECO:0000269|PubMed:23320472, ECO:0000269|PubMed:23913813, ECO:0000269|PubMed:24739679}. 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 KABUK1.
Any additional useful information about the variant.



Sequence information

Variant position:  5340
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  5537
The length of the canonical sequence.

Location on the sequence:   RYGRHPLMELPLMINPTGCA  R SEPKILTHYKRPHTLNSTSM
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                         RYGRHPLMELPLMINPTGCARSEPKILTHYKRPHTLNSTSM

Mouse                         RYGRHPLMELPLMINPTGCARSEPKILTHYKRPHTLNSTSM

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 – 5537 Histone-lysine N-methyltransferase 2D
Helix 5339 – 5341


Literature citations

Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome.
Ng S.B.; Bigham A.W.; Buckingham K.J.; Hannibal M.C.; McMillin M.J.; Gildersleeve H.I.; Beck A.E.; Tabor H.K.; Cooper G.M.; Mefford H.C.; Lee C.; Turner E.H.; Smith J.D.; Rieder M.J.; Yoshiura K.; Matsumoto N.; Ohta T.; Niikawa N.; Nickerson D.A.; Bamshad M.J.; Shendure J.;
Nat. Genet. 42:790-793(2010)
Cited for: VARIANTS KABUK1 PHE-5109; HIS-5179; HIS-5214; LEU-5340 AND MET-5464; INVOLVEMENT IN KABUK1;

Spectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome.
Hannibal M.C.; Buckingham K.J.; Ng S.B.; Ming J.E.; Beck A.E.; McMillin M.J.; Gildersleeve H.I.; Bigham A.W.; Tabor H.K.; Mefford H.C.; Cook J.; Yoshiura K.; Matsumoto T.; Matsumoto N.; Miyake N.; Tonoki H.; Naritomi K.; Kaname T.; Nagai T.; Ohashi H.; Kurosawa K.; Hou J.W.; Ohta T.; Liang D.; Sudo A.; Morris C.A.; Banka S.; Black G.C.; Clayton-Smith J.; Nickerson D.A.; Zackai E.H.; Shaikh T.H.; Donnai D.; Niikawa N.; Shendure J.; Bamshad M.J.;
Am. J. Med. Genet. A 155A:1511-1516(2011)
Cited for: VARIANTS KABUK1 LEU-1388; ARG-1430; TYR-1471; CYS-5048; PHE-5109; HIS-5179; CYS-5214; HIS-5214; LEU-5340; MET-5464 AND THR-5471;

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.