KMT2B

lysine methyltransferase 2B, the group of PHD finger proteins|SET domain containing|Zinc fingers CXXC-type|Lysine methyltransferases

Basic information

Region (hg38): 19:35717973-35738880

Links

ENSG00000272333 ∙ NCBI:9757 ∙ OMIM:606834 ∙ HGNC:15840 ∙ Uniprot:Q9UMN6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dystonia 28, childhood-onset (Definitive), mode of inheritance: AD
• complex neurodevelopmental disorder with motor features (Definitive), mode of inheritance: AD
• dystonia 28, childhood-onset (Strong), mode of inheritance: AD
• intellectual developmental disorder, autosomal dominant 68 (Limited), mode of inheritance: Unknown
• dystonia 28, childhood-onset (Strong), mode of inheritance: AD
• dystonia 28, childhood-onset (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dystonia 28, childhood-onset; Intellectual developmental disorder, autosomal dominant 68	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	27839873; 27992417; 29276005; 33150406
In Dystonia 28, surgical treatment (with deep brain stimulation) has been reported as effective

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KMT2B gene.

• not_provided (2209 variants)
• Inborn_genetic_diseases (414 variants)
• Dystonia_28,_childhood-onset (124 variants)
• KMT2B-related_disorder (68 variants)
• not_specified (43 variants)
• Intellectual_developmental_disorder,_autosomal_dominant_68 (37 variants)
• Intellectual_disability (12 variants)
• See_cases (4 variants)
• Dystonic_disorder (3 variants)
• Dysarthria (3 variants)
• Complex_neurodevelopmental_disorder_with_motor_features (2 variants)
• Generalized_dystonia (2 variants)
• Dystonia,_early-onset,_and/or_spastic_paraplegia (1 variants)
• Myoclonus (1 variants)
• Autism_spectrum_disorder (1 variants)
• Epilepsy,_idiopathic_generalized,_susceptibility_to,_5 (1 variants)
• Castleman-Kojima_disease (1 variants)
• Global_developmental_delay (1 variants)
• Specific_learning_disability (1 variants)
• Abnormality_of_metabolism/homeostasis (1 variants)
• Autism (1 variants)
• Rare_genetic_intellectual_disability (1 variants)
• Poor_motor_coordination (1 variants)
• Kabuki_syndrome_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KMT2B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014727.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		9	467	148	625
missense	2	32	891	407	87	1419
nonsense	15	12	3			30
start loss						0
frameshift	64	14	2		1	81
splice donor/acceptor (+/-2bp)	2	2	16	1		21
Total	84	60	921	875	236

Highest pathogenic variant AF is 0.000007529935

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KMT2B	protein_coding	protein_coding	ENST00000222270	37	20859

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		123835	0	7	123842	0.0000283

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.43	1209	1.59e+3	0.759	0.000106	16961
Missense in Polyphen		322	610.29	0.52762		6075
Synonymous	-4.28	776	639	1.22	0.0000426	5927
Loss of Function	9.52	3	111	0.0269	0.00000640	1224

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000300	0.0000300
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000142	0.000140
European (Non-Finnish)	0.0000286	0.0000268
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Histone methyltransferase. Methylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Plays a central role in beta-globin locus transcription regulation by being recruited by NFE2. Plays an important role in controlling bulk H3K4me during oocyte growth and preimplantation development. Required during the transcriptionally active period of oocyte growth for the establishment and/or maintenance of bulk H3K4 trimethylation (H3K4me3), global transcriptional silencing that preceeds resumption of meiosis, oocyte survival and normal zygotic genome activation. {ECO:0000269|PubMed:17707229}.
• 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;Chromatin organization;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

• pRec: 0.105

Intolerance Scores

• rvis_EVS: -5.29
• rvis_percentile_EVS: 0.06

Essentials

• essential_gene_CRISPR: N

Gene Damage Prediction

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

Gene ontology

• Biological process: ovarian follicle development;regulation of transcription by RNA polymerase II;memory;oocyte differentiation;gene silencing;ovulation;regulation of megakaryocyte differentiation;chromatin-mediated maintenance of transcription;histone H3-K4 methylation;regulation of histone H3-K4 methylation;histone H3-K4 trimethylation
• Cellular component: nucleus;nucleoplasm;histone methyltransferase complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;zinc ion binding;histone-lysine N-methyltransferase activity;histone methyltransferase activity (H3-K4 specific)