KMT2E (lysine methyltransferase 2E (inactive))

Gene

• Entrez ID: 55904
• Gene name: Lysine methyltransferase 2E (inactive)
• Gene symbol: KMT2E
• Synonyms (NCBI Gene): HDCMC04P, MLL5, NKp44L, ODLURO, SETD5B
• Chromosome: 7
• Chromosome location: 7q22.3
• Summary: This gene is a member of the myeloid/lymphoid or mixed-lineage leukemia (MLL) family and encodes a protein with an N-terminal PHD zinc finger and a central SET domain. Overexpression of the protein inhibits cell cycle progression. Alternate transcriptiona

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs74375534	G>A,T	Uncertain-significance, pathogenic	Missense variant, 5 prime UTR variant, non coding transcript variant, coding sequence variant
rs186916831	C>G,T	Pathogenic, likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant, stop gained
rs1554394210	T>C	Likely-pathogenic, uncertain-significance	Splice donor variant
rs1562927768	AAAGA>-	Pathogenic, likely-pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1562928193	->TA	Likely-pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs1562931936	C>T	Likely-pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs1584751177	->T	Pathogenic	Stop gained, coding sequence variant, non coding transcript variant
rs1584796761	G>T	Likely-pathogenic	Stop gained, coding sequence variant, non coding transcript variant
rs1584802161	C>-	Likely-pathogenic	Stop gained, coding sequence variant, non coding transcript variant
rs1584802744	C>T	Likely-pathogenic, pathogenic	Stop gained, coding sequence variant, non coding transcript variant
rs1584803713	ACTA>-	Likely-pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant
rs1584803745	C>T	Likely-pathogenic	Stop gained, coding sequence variant, non coding transcript variant
rs1584803942	A>T	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1584805072	T>-	Likely-pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant
rs1584807827	GA>-	Likely-pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant
rs1584808269	TA>-	Likely-pathogenic	Stop gained, inframe indel, coding sequence variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017069	hsa-miR-335-5p	Microarray	18185580
MIRT036034	hsa-miR-1301-3p	CLASH	23622248
MIRT727181	hsa-miR-181a-5p	HITS-CLIP	22473208
MIRT727180	hsa-miR-181b-5p	HITS-CLIP	22473208
MIRT727178	hsa-miR-181c-5p	HITS-CLIP	22473208
MIRT727179	hsa-miR-181d-5p	HITS-CLIP	22473208

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	IDA	23798402
GO:0000791	Component	Euchromatin	IDA	23798402
GO:0002446	Process	Neutrophil mediated immunity	IEA
GO:0002446	Process	Neutrophil mediated immunity	ISS
GO:0003713	Function	Transcription coactivator activity	IDA	23629655
GO:0005515	Function	Protein binding	IPI	21423215, 23629655, 23958951, 32296183
GO:0005634	Component	Nucleus	IDA	23629655, 26678539
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	IEA
GO:0005694	Component	Chromosome	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005813	Component	Centrosome	IEA
GO:0005856	Component	Cytoskeleton	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0006325	Process	Chromatin organization	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IBA
GO:0008270	Function	Zinc ion binding	IEA
GO:0010468	Process	Regulation of gene expression	IEA
GO:0016020	Component	Membrane	IEA
GO:0016604	Component	Nuclear body	IDA
GO:0016607	Component	Nuclear speck	IEA
GO:0019899	Function	Enzyme binding	IPI	23629655, 26678539
GO:0030218	Process	Erythrocyte differentiation	IEA
GO:0030218	Process	Erythrocyte differentiation	ISS
GO:0032991	Component	Protein-containing complex	IDA	23629655, 26678539
GO:0034967	Component	Set3 complex	IBA
GO:0040029	Process	Epigenetic regulation of gene expression	IEA
GO:0040029	Process	Epigenetic regulation of gene expression	ISS
GO:0042119	Process	Neutrophil activation	IEA
GO:0042119	Process	Neutrophil activation	ISS
GO:0045893	Process	Positive regulation of DNA-templated transcription	IMP	23629655
GO:0046872	Function	Metal ion binding	IEA
GO:0051726	Process	Regulation of cell cycle	IEA
GO:0070210	Component	Rpd3L-Expanded complex	IBA
GO:0140002	Function	Histone H3K4me3 reader activity	IDA	24130829
GO:0140002	Function	Histone H3K4me3 reader activity	IMP	23798402
GO:0140938	Function	Histone H3 methyltransferase activity	IDA	27812132
GO:1900087	Process	Positive regulation of G1/S transition of mitotic cell cycle	IMP	23629655

Other IDs

• MIM: 608444
• HGNC: 18541
• e!Ensembl: ENSG00000005483

Protein

• UniProt ID: Q8IZD2
• Protein name: Inactive histone-lysine N-methyltransferase 2E (Inactive lysine N-methyltransferase 2E) (Myeloid/lymphoid or mixed-lineage leukemia protein 5)
• Protein function: Associates with chromatin regions downstream of transcriptional start sites of active genes and thus regulates gene transcription (PubMed:23629655, PubMed:23798402, PubMed:24130829). Chromatin interaction is mediated via the binding to tri-methy
• PDB: 2LV9, 4L58, 5HT6
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00628	PHD	120 → 166	PHD-finger	Domain
  PF00856	SET	155 → 447	SET domain	Family

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed in both adult and fetal tissues (PubMed:12101424, PubMed:23958951). Highest levels of expression observed in fetal thymus and kidney and in adult hematopoietic tissues, jejunum and cerebellum (PubMed:12101424, PubMed:2
• Sequence:

  MSIVIPLGVDTAETSYLEMAAGSEPESVEASPVVVEKSNSYPHQLYTSSSHHSHSYIGLP
  YADHNYGARPPPTPPASPPPSVLISKNEVGIFTTPNFDETSSATTISTSEDGSYGTDVTR
  CICGFTHDDGYMICCDKCSVWQHIDCMGIDRQHIPDTYLCERCQPRNLDKERAVLLQRRK
  RENMSDGDTSATESGDEVPVELYTAFQHTPTSITLTASRVSKVNDKRRKKSGEKEQHISK
  CKKAFREGSRKSSRVKGSAPEIDPSSDGSNFGWETKIKAWMDRYEEANNNQYSEGVQREA
  QRIALRLGNGNDKKEMNKSDLNTNNLLFKPPVESHIQKNKKILKSAKDLPPDALIIEYRG
  KFMLREQFEANGYFFKRPYPFVLFYSKFHGLEMCVDARTFGNEARFIRRSCTPNAEVRHE
  IQDGTIHLYIYSIHSIPKGTEITIAFDFDYGNCKYKVDCACLKENPECPVLKRSSESMEN
  INSGYETRRKKGKKDKDISKEKDTQNQNITLDCEGTTNKMKSPETKQRKLSPLRLSVSNN
  QEPDFIDDIEEKTPISNEVEMESEEQIAERKRKMTREERKMEAILQAFARLEKREKRREQ
  ALERISTAKTEVKTECKDTQIVSDAEVIQEQAKEENASKPTPAKVNRTKQRKSFSRSRTH
  IGQQRRRHRTVSMCSDIQPSSPDIEVTSQQNDIENTVLTIEPETETALAEIITETEVPAL
  NKCPTKYPKTKKHLVNEWLSEKNEKTGKPSDGLSERPLRITTDPEVLATQLNSLPGLTYS
  PHVYSTPKHYIRFTSPFLSEKRRRKEPTENISGSCKKRWLKQALEEENSAILHRFNSPCQ
  ERSRSPAVNGENKSPLLLNDSCSLPDLTTPLKKRRFYQLLDSVYSETSTPTPSPYATPTH
  TDITPMDPSFATPPRIKSDDETCRNGYKPIYSPVTPVTPGTPGNTMHFENISSPESSPEI
  KRRTYSQEGYDRSSTMLTLGPFRNSNLTELGLQEIKTIGYTSPRSRTEVNRQCPGEKEPV
  SDLQLGLDAVEPTALHKTLETPAHDRAEPNSQLDSTHSGRGTMYSSWVKSPDRTGVNFSV
  NSNLRDLTPSHQLEVGGGFRISESKCLMQDDTRGMFMETTVFCTSEDGLVSGFGRTVNDN
  LIDGNCTPQNPPQKKKVSLLEYRKRQREARKSGSKTENFPLISVSPHASGSLSNNGDGCA
  SSNDNGEQVDHTASLPLPTPATVYNATSEETSNNCPVKDATASEKNEPEVQWTASTSVEQ
  VRERSYQRALLLSDHRKDKDSGGESPCVSCSPSHVQSSPSSHSNHIPQLQAKGPVPSFSE
  LMEDPDPENPEPTTTNECPSPDTSQNTCKSPPKMSKPGSPGSVIPAQAHGKIFTKPDPQW
  DSTVSASEAENGVHLKTELQQKQLSNNNQALSKNHPPQTHVRNSSEQLSQKLPSVPTKLH
  CPPSPHLENPPKSSTPHTPVQHGYLSPKPPSQQLGSPYRPHHSQSPQVGTPQREPQRNFY
  PAAQNLPANTQQATSGTLFTQTPSGQSSATYSQFNQQSLNSTAPPPPPPPPPSSSYYQNQ
  QPSANFQNYNQLKGSLSQQTVFTSGPNQALPGTTSQQTVPGHHVTPGHFLPSQNPTIHHQ
  TAAAVVPPPPPPPPAPGPHLVQQPNSHQQHSVAHVVGPVHAVTPGSHIHSQTAGHHLPPP
  PPPPGPAPHHHPPPHPSTGLQGLQAQHQHVVNSAPPPPPPPPPSSVLASGHHTTSAQALH
  HPPHQGPPLFPSSAHPTVPPYPSQATHHTTLGPGPQHQPSGTGPHCPLPVTGPHLQPQGP
  NSIPTPTASGFCPHPGSVALPHGVQGPQQASPVPGQIPIHRAQVPPTFQNNYHGSGWH

• Sequence length: 1858

Pathways

KEGG:

Lysine degradation
Metabolic pathways

Reactome:

PKMTs methylate histone lysines
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Global developmental delay	Likely pathogenic; Pathogenic	rs777413129	RCV002463863
Intellectual disability	Pathogenic	rs1562928193	RCV000735811
KMT2E-related disorder	Likely pathogenic; Pathogenic	rs1243172283, rs2536523348	RCV004743443 RCV003982806
Neurodevelopmental delay	Pathogenic; Likely pathogenic	rs2129569915, rs2129568394	RCV002274353 RCV002274412
Neurodevelopmental disorder	Likely pathogenic; Pathogenic	rs2129567978, rs2536417191, rs1798679896	RCV002277706 RCV004018304 RCV001267669
Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies	Likely pathogenic	rs2129570184	RCV001823316
O'Donnell-Luria-Rodan syndrome	Likely pathogenic; Pathogenic	rs1798939855, rs2129567233, rs1243172283, rs2129565360, rs2129567141, rs2129567228, rs2129568047, rs2129568919, rs1476442868, rs2129569834, rs2129569867, rs2129569889, rs2129570178, rs1479029169, rs1295432172, rs1799182705, rs2129569484, rs1796899754, rs2536506538, rs2536518341, rs777413129, rs2536525829, rs772510917, rs2536462095, rs2536461799, rs2536502995, rs2536517599, rs2536513831, rs2536462068, rs2536432550, rs2536381910, rs2536428687, rs2536520170, rs2536465540, rs2536420410, rs2536504223, rs2536493815, rs1562928193, rs1562927768, rs1562931936, rs1584802744, rs186916831, rs1584751177, rs1584803942, rs1584808269, rs1799183455, rs1799378709, rs1797574932, rs1798679896	RCV001331058 RCV004017834 RCV001420174 RCV001420170 RCV001420176 RCV001420177 RCV001420178 RCV001420171 RCV001420172 RCV001420173 RCV001420179 RCV001420168 RCV001420169 RCV001733801 RCV005868362 RCV002226811 RCV002275721 RCV002285194 RCV002289162 RCV002289469 RCV003329125 RCV002468735 RCV002471863 RCV002470579 RCV002510313 RCV006249838 RCV003123250 RCV003127420 RCV003148480 RCV003152841 RCV003314169 RCV003388335 RCV003458975 RCV003494071 RCV003984917 RCV003985231 RCV004018025 RCV001420166 RCV000790637 RCV004788153 RCV000790635 RCV000790636 RCV000790638 RCV000790640 RCV003325983 RCV001193353 RCV001420175 RCV001261985 RCV001420167
See cases	Likely pathogenic; Pathogenic	rs2129568923, rs2536490764, rs1562927768, rs1562931936, rs1584802744, rs186916831, rs1584803942, rs1584802161, rs1584803713, rs1584803745, rs1584805072, rs1584817521, rs1584819461, rs1584807827, rs1584808269	RCV002252507 RCV002287757 RCV000993722 RCV000993729 RCV000993725 RCV000993733 RCV000993740 RCV000993724 RCV000993726 RCV000993727 RCV000993728 RCV000993734 RCV000993736 RCV000993760 RCV000993761

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Abnormal cerebellar vermis morphology	Uncertain significance	rs1797560918	RCV001391290
Acute myeloid leukemia	Benign; Likely benign	rs60766560, rs201147710	RCV005926238 RCV005928449
Autism spectrum disorder	Likely benign	rs2536461754	RCV003127419
Cervical cancer	Benign	rs60766560	RCV005926240
Complex neurodevelopmental disorder	Conflicting classifications of pathogenicity	rs2536527907	RCV003994455
Familial pancreatic carcinoma	Benign	rs60766560	RCV005926241
Gastric cancer	Benign	rs60766560	RCV005926243
Intellectual disability, autosomal dominant 40	Conflicting classifications of pathogenicity	rs201601985	RCV002466937
Malignant tumor of esophagus	Benign	rs60766560	RCV005926239
Malignant tumor of urinary bladder	Uncertain significance	rs1299577458	RCV005920758
Nonpapillary renal cell carcinoma	Uncertain significance	rs757830237	RCV005934703
Ovarian serous cystadenocarcinoma	Benign; Conflicting classifications of pathogenicity	rs60766560, rs1584761229	RCV005926244 RCV005912198
Sarcoma	Benign	rs60766560	RCV005926242
Squamous cell lung carcinoma	Likely benign	rs757593144	RCV005934846

Associations from Text Mining
Disease Name	Relationship Type	References
Adenocarcinoma	Associate	26678539
Autism Spectrum Disorder	Associate	25284784
Autistic Disorder	Associate	31079897
Brain Diseases	Associate	31079897
COVID 19	Associate	33936072
Developmental Disabilities	Associate	31079897, 34321323, 38453051, 39709003
Ectrodactyly	Associate	29447242
Epilepsy	Associate	31079897
Epilepsy Generalized	Associate	39709003
Fetal Alcohol Spectrum Disorders	Associate	31079897
HIV Infections	Associate	29447242
Intellectual Disability	Associate	31079897
Leukemia Promyelocytic Acute	Associate	24796963, 33824267
Megalencephaly	Associate	34321323
Microcephaly	Associate	31079897
Neoplasms	Inhibit	20439461
Neoplasms	Associate	23958951, 26678539, 33050986
O'Donnell Pappas syndrome	Associate	34321323, 39709003
Prostatic Neoplasms	Associate	33050986