Kleefstra syndrome (Homo sapiens)
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Description
Kleefstra syndrome is a rare genetic disorder (MIM #610253, Orpha:261494). The cause was found first to be a deletion in the region 9q34.2 with the main gene EHMT1, which is a histone methyltransferase and involved in epigenetics, namely histone methylation on histone H3 lysine residues. It also methylates DNA. Similar phenotypes were later found with loss of function mutations in other proteins involved in histone methylation, namely KMT2C (MLL3) located on 7q36.1, MBD5, SMARCB1, and NR1I3 (MIM #617768 Kleefstra syndrome 2).
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Ontology Terms
Bibliography
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- Shinsky SA, Monteith KE, Viggiano S, Cosgrove MS; ''Biochemical reconstitution and phylogenetic comparison of human SET1 family core complexes involved in histone methylation.''; J Biol Chem, 2015 PubMed Europe PMC Scholia
- Ogawa H, Ishiguro K, Gaubatz S, Livingston DM, Nakatani Y; ''A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells.''; Science, 2002 PubMed Europe PMC Scholia
- Goo YH, Sohn YC, Kim DH, Kim SW, Kang MJ, Jung DJ, Kwak E, Barlev NA, Berger SL, Chow VT, Roeder RG, Azorsa DO, Meltzer PS, Suh PG, Song EJ, Lee KJ, Lee YC, Lee JW; ''Activating signal cointegrator 2 belongs to a novel steady-state complex that contains a subset of trithorax group proteins.''; Mol Cell Biol, 2003 PubMed Europe PMC Scholia
- Park SH, Ayoub A, Lee YT, Xu J, Kim H, Zheng W, Zhang B, Sha L, An S, Zhang Y, Cianfrocco MA, Su M, Dou Y, Cho US; ''Cryo-EM structure of the human MLL1 core complex bound to the nucleosome.''; Nat Commun, 2019 PubMed Europe PMC Scholia
- Baymaz HI, Fournier A, Laget S, Ji Z, Jansen PW, Smits AH, Ferry L, Mensinga A, Poser I, Sharrocks A, Defossez PA, Vermeulen M; ''MBD5 and MBD6 interact with the human PR-DUB complex through their methyl-CpG-binding domain.''; Proteomics, 2014 PubMed Europe PMC Scholia
- Chang Y, Ganesh T, Horton JR, Spannhoff A, Liu J, Sun A, Zhang X, Bedford MT, Shinkai Y, Snyder JP, Cheng X; ''Adding a lysine mimic in the design of potent inhibitors of histone lysine methyltransferases.''; J Mol Biol, 2010 PubMed Europe PMC Scholia
- Cho YW, Hong T, Hong S, Guo H, Yu H, Kim D, Guszczynski T, Dressler GR, Copeland TD, Kalkum M, Ge K; ''PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 methyltransferase complex.''; J Biol Chem, 2007 PubMed Europe PMC Scholia
- van Nuland R, Smits AH, Pallaki P, Jansen PW, Vermeulen M, Timmers HT; ''Quantitative dissection and stoichiometry determination of the human SET1/MLL histone methyltransferase complexes.''; Mol Cell Biol, 2013 PubMed Europe PMC Scholia
- Kleefstra T, van Zelst-Stams WA, Nillesen WM, Cormier-Daire V, Houge G, Foulds N, van Dooren M, Willemsen MH, Pfundt R, Turner A, Wilson M, McGaughran J, Rauch A, Zenker M, Adam MP, Innes M, Davies C, López AG, Casalone R, Weber A, Brueton LA, Navarro AD, Bralo MP, Venselaar H, Stegmann SP, Yntema HG, van Bokhoven H, Brunner HG; ''Further clinical and molecular delineation of the 9q subtelomeric deletion syndrome supports a major contribution of EHMT1 haploinsufficiency to the core phenotype.''; J Med Genet, 2009 PubMed Europe PMC Scholia
- Zhang P, Lee H, Brunzelle JS, Couture JF; ''The plasticity of WDR5 peptide-binding cleft enables the binding of the SET1 family of histone methyltransferases.''; Nucleic Acids Res, 2012 PubMed Europe PMC Scholia
- Kleefstra T, Kramer JM, Neveling K, Willemsen MH, Koemans TS, Vissers LE, Wissink-Lindhout W, Fenckova M, van den Akker WM, Kasri NN, Nillesen WM, Prescott T, Clark RD, Devriendt K, van Reeuwijk J, de Brouwer AP, Gilissen C, Zhou H, Brunner HG, Veltman JA, Schenck A, van Bokhoven H; ''Disruption of an EHMT1-associated chromatin-modification module causes intellectual disability.''; Am J Hum Genet, 2012 PubMed Europe PMC Scholia
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
ACTL6A | GeneProduct | ENSG00000136518 (Ensembl) ![]() | |
ACTL6B | GeneProduct | ENSG00000077080 (Ensembl) ![]() | |
ARID1A | GeneProduct | ENSG00000117713 (Ensembl) ![]() | |
ARID1B | GeneProduct | ENSG00000049618 (Ensembl) ![]() | |
ASC-2/NCOA6 complex (ASCOM) | Complex | CPX-7091 (Complex Portal) ![]() | |
ASH2L | GeneProduct | ENSG00000129691 (Ensembl) ![]() | |
ASXL1 | GeneProduct | ENSG00000171456 (Ensembl) ![]() | |
BAP1 | GeneProduct | ENSG00000163930 (Ensembl) ![]() | |
BIX-01294 | Metabolite | 93986 (ChEBI) ![]() | 6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-[1-(phenylmethyl)-4-piperidinyl]-4-quinazolinamine |
DNA | Metabolite | CHEBI:16991 (ChEBI) ![]() | |
DPY30 | GeneProduct | ENSG00000162961 (Ensembl) ![]() | |
EHMT1 | GeneProduct | ENSG00000181090 (Ensembl) ![]() | |
Histone H3.3 | GeneProduct | P84243 (Uniprot-TrEMBL) ![]() | |
Histone modifications | Pathway | WP2369 (WikiPathways) ![]() | |
KDM6A | GeneProduct | ENSG00000147050 (Ensembl) ![]() | |
KMT2C | GeneProduct | MLL3 | |
KMT2C | GeneProduct | ENSG00000055609 (Ensembl) ![]() | MLL3 |
L-lysine residue | Metabolite | 29969 (ChEBI) ![]() | |
MBD5 | GeneProduct | ENSG00000204406 (Ensembl) ![]() | |
N6,N6-dimethyl-L-lysine residue | Metabolite | 61976 (ChEBI) ![]() | |
N6-methyl-L-lysine residue | Metabolite | 61929 (ChEBI) ![]() | |
NCOA6 | GeneProduct | ENSG00000198646 (Ensembl) ![]() | |
NR1I3 | GeneProduct | ENSG00000143257 (Ensembl) ![]() | |
PAGR1 | GeneProduct | ENSG00000280789 (Ensembl) ![]() | |
PAXIP1 | GeneProduct | ENSG00000157212 (Ensembl) ![]() | |
Polycomb repressive deubiquitinase (PR-DUB) complex | Complex | ||
RBBP5 | GeneProduct | ENSG00000117222 (Ensembl) ![]() | |
RXRA | GeneProduct | ENSG00000186350 (Ensembl) ![]() | |
S-adenosyl-L-homocysteine | Metabolite | 57856 (ChEBI) ![]() | |
S-adenosyl-L-methionine | Metabolite | 59789 (ChEBI) ![]() | |
SMARCA2 | GeneProduct | ENSG00000080503 (Ensembl) ![]() | |
SMARCA4 | GeneProduct | ENSG00000127616 (Ensembl) ![]() | |
SMARCB1 | GeneProduct | ENSG00000099956 (Ensembl) ![]() | |
SMARCC1 | GeneProduct | ENSG00000173473 (Ensembl) ![]() | |
SMARCC2 | GeneProduct | ENSG00000139613 (Ensembl) ![]() | |
SMARCD1 | GeneProduct | ENSG00000066117 (Ensembl) ![]() | |
SMARCD2 | GeneProduct | ENSG00000108604 (Ensembl) ![]() | |
SMARCD3 | GeneProduct | ENSG00000082014 (Ensembl) ![]() | |
SWI/SNF complex | Complex | ||
WDR5 | GeneProduct | ENSG00000196363 (Ensembl) ![]() | |
Zn(2+) | Metabolite | 29105 (ChEBI) ![]() |
Annotated Interactions
Source | Target | Type | Database reference | Comment |
---|---|---|---|---|
KMT2C | mim-catalysis | 60264 (Rhea) ![]() | ||
N6-methyl-L-lysine residue | N6,N6-dimethyl-L-lysine residue | mim-conversion | 60284 (Rhea) ![]() | |
S-adenosyl-L-methionine | S-adenosyl-L-homocysteine | mim-conversion | 60284 (Rhea) ![]() |