KMT2E

lysine methyltransferase 2E (inactive), the group of PHD finger proteins|SET domain containing|Lysine methyltransferases

Basic information

Region (hg38): 7:104940943-105115019

Previous symbols: [ "MLL5" ]

Links

ENSG00000005483

∙ NCBI:55904 ∙ OMIM:608444 ∙ HGNC:18541 ∙ Uniprot:Q8IZD2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

intellectual disability, autosomal dominant 40 (Definitive), mode of inheritance: AD
O'Donnell-Luria-Rodan syndrome (Moderate), mode of inheritance: AD
O'Donnell-Luria-Rodan syndrome (Strong), mode of inheritance: AD
syndromic intellectual disability (Supportive), mode of inheritance: AD
O'Donnell-Luria-Rodan syndrome (Strong), mode of inheritance: AD
complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
O'Donnell-Luria-Rodan syndrome	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic	31079897

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KMT2E gene.

not provided (20 variants)
O'Donnell-Luria-Rodan syndrome (16 variants)
Inborn genetic diseases (6 variants)
Intellectual disability (1 variants)
Neurodevelopmental disorder (1 variants)
Neurodevelopmental delay (1 variants)
See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KMT2E gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1 clinvar	1 clinvar	147 clinvar	15 clinvar	164
missense		6 clinvar	362 clinvar	36 clinvar	41 clinvar	445
nonsense	13 clinvar	13 clinvar	1 clinvar		1 clinvar	28
start loss						0
frameshift	29 clinvar	22 clinvar	17 clinvar			68
inframe indel		1 clinvar	22 clinvar	5 clinvar		28
splice donor/acceptor (+/-2bp)		6 clinvar	2 clinvar	1 clinvar		9
splice region		2	9	17	5	33
non coding		1 clinvar	6 clinvar	54 clinvar	13 clinvar	74
Total	42	50	411	243	70

Variants in KMT2E

This is a list of pathogenic ClinVar variants found in the KMT2E region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Phenotype	Significance	ClinVar
7-105040858-A-G		Uncertain significance (Feb 27, 2023)	2577643
7-105040965-A-T	O'Donnell-Luria-Rodan syndrome	Uncertain significance (Aug 15, 2023)	2582434
7-105040966-T-A	O'Donnell-Luria-Rodan syndrome	Uncertain significance (Nov 04, 2022)	2433253
7-105040970-A-G		Likely benign (Jun 20, 2022)	2103336
7-105040971-T-C		Likely benign (Mar 24, 2023)	1991947
7-105040973-G-A	KMT2E-related disorder	Likely benign (Dec 17, 2023)	2150692
7-105040984-C-T		Uncertain significance (Aug 02, 2023)	2787715
7-105040994-G-A	KMT2E-related disorder	Benign (Jan 04, 2024)	2065812
7-105041005-A-G		Uncertain significance (Aug 13, 2019)	1307497
7-105041015-AG-A	O'Donnell-Luria-Rodan syndrome	Likely pathogenic (Apr 28, 2021)	1098297
7-105041020-C-T		Uncertain significance (Jun 07, 2023)	3252452
7-105041042-TA-T		Likely benign (Dec 26, 2023)	2877998
7-105062147-C-G		Benign (Feb 01, 2024)	1657509
7-105062155-T-TC	KMT2E-related disorder	Benign (Apr 05, 2022)	2417530
7-105062156-C-T		Benign/Likely benign (Dec 14, 2023)	2160341
7-105062167-A-G		Benign/Likely benign (Mar 01, 2024)	2155328
7-105062173-C-T		Likely benign (Aug 22, 2023)	2881644
7-105062174-G-A		Uncertain significance (Jul 28, 2023)	2710156
7-105062191-G-C		Likely benign (May 31, 2023)	2754450
7-105062196-T-C		Benign (Dec 06, 2023)	2777654
7-105062198-G-C		Uncertain significance (Jun 05, 2024)	1693394
7-105062228-T-C		Uncertain significance (Oct 15, 2023)	2783535
7-105062234-A-G	KMT2E-related disorder	Uncertain significance (Dec 16, 2023)	3015598
7-105062239-C-T		Likely benign (Jan 16, 2022)	1975039
7-105062258-TA-T	See cases	Uncertain significance (Feb 07, 2019)	805896

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KMT2E	protein_coding	protein_coding	ENST00000311117	25	100183

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.59e-12	125706	0	39	125745	0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.42	849	974	0.872	0.0000500	12103
Missense in Polyphen		39	47.469	0.82158		441
Synonymous	-2.60	410	348	1.18	0.0000186	3673
Loss of Function	8.11	1	78.6	0.0127	0.00000376	1044

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000383	0.000359
Ashkenazi Jewish	0.00	0.00
East Asian	0.000285	0.000272
Finnish	0.0000958	0.0000924
European (Non-Finnish)	0.000156	0.000149
Middle Eastern	0.000285	0.000272
South Asian	0.000298	0.000294
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Associates with chromatin regions downstream of transcriptional start sites of active genes and thus regulates gene transcription (PubMed:23629655, PubMed:24130829, PubMed:23798402). Chromatin interaction is mediated via the binding to tri-methylated histone H3 at 'Lys-4' (H3K4me3) (PubMed:24130829, PubMed:23798402). Key regulator of hematopoiesis involved in terminal myeloid differentiation and in the regulation of hematopoietic stem cell (HSCs) self-renewal by a mechanism that involves DNA methylation (By similarity). Also acts as an important cell cycle regulator, participating in cell cycle regulatory network machinery at multiple cell cycle stages including G1/S transition, S phase progression and mitotic entry (PubMed:14718661, PubMed:18573682, PubMed:19264965, PubMed:23629655). Recruited to E2F1 responsive promoters by HCFC1 where it stimulates tri-methylation of histone H3 at 'Lys-4' and transcriptional activation and thereby facilitates G1 to S phase transition (PubMed:23629655). During myoblast differentiation, required to suppress inappropriate expression of S-phase-promoting genes and maintain expression of determination genes in quiescent cells (By similarity). {ECO:0000250|UniProtKB:Q3UG20, ECO:0000269|PubMed:14718661, ECO:0000269|PubMed:18573682, ECO:0000269|PubMed:23629655, ECO:0000269|PubMed:23798402, ECO:0000269|PubMed:24130829}.;
Pathway: Lysine degradation - Homo sapiens (human);Histone Modifications;Gene expression (Transcription);Generic Transcription Pathway;PKMTs methylate histone lysines;RNA Polymerase II Transcription;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;Chromatin modifying enzymes;Glycosphingolipid metabolism;Chromatin organization;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

pRec: 0.114

Intolerance Scores

loftool
rvis_EVS: -1.45
rvis_percentile_EVS: 3.9

Haploinsufficiency Scores

pHI: 0.431
hipred: Y
hipred_score: 0.613
ghis: 0.622

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2
essential_gene_gene_trap: N
gene_indispensability_pred
gene_indispensability_score

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Kmt2e
Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; hematopoietic system phenotype; vision/eye phenotype;

Gene ontology

Biological process: neutrophil mediated immunity;DNA methylation;cell cycle arrest;erythrocyte differentiation;histone lysine methylation;neutrophil activation;regulation of megakaryocyte differentiation;positive regulation of transcription, DNA-templated;positive regulation of G1/S transition of mitotic cell cycle;positive regulation of histone H3-K4 trimethylation
Cellular component: chromatin;nucleus;nucleoplasm;cytoplasm;microtubule organizing center;plasma membrane;nuclear speck;protein-containing complex;transcriptionally active chromatin
Molecular function: protein binding;histone-lysine N-methyltransferase activity;enzyme binding;methylated histone binding;metal ion binding