KMT2B

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

Basic information

Region (hg38): 19:35717972-35738880

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 (Strong), mode of inheritance: AD
• dystonia 28, childhood-onset (Definitive), mode of inheritance: AD
• dystonia 28, childhood-onset (Supportive), mode of inheritance: AD
• dystonia 28, childhood-onset (Strong), mode of inheritance: AD
• intellectual developmental disorder, autosomal dominant 68 (Limited), mode of inheritance: Unknown
• complex neurodevelopmental disorder with motor features (Definitive), 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 (1190 variants)
• Inborn genetic diseases (141 variants)
• Dystonia 28, childhood-onset (88 variants)
• KMT2B-related condition (17 variants)
• not specified (12 variants)
• Intellectual developmental disorder, autosomal dominant 68 (7 variants)
• Intellectual disability (5 variants)
• See cases (3 variants)
• Kabuki syndrome 1 (1 variants)
• Global developmental delay (1 variants)
• Autism spectrum disorder (1 variants)
• KMT2B-related disorders (1 variants)
• Intellectual developmental disorder, autosomal dominant 68;Dystonia 28, childhood-onset (1 variants)
• Poor motor coordination;Generalized dystonia;Dysarthria (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.

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		4	236	98	339
missense	1	25	416	161	40	643
nonsense	11	6				17
start loss						0
frameshift	44	8	1		1	54
inframe indel			20	3	1	24
splice donor/acceptor (+/-2bp)	2	2	1	1		6
splice region			14	29	7	50
non coding			11	92	55	158
Total	59	41	453	493	195

Highest pathogenic variant AF is 0.0000132

Variants in KMT2B

This is a list of pathogenic ClinVar variants found in the KMT2B region.

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

Position	Type	Phenotype	Significance	ClinVar
19-35718020-TGGCGGCGGCGGCG-T			Pathogenic (May 29, 2021)
19-35718020-T-TGGC			Likely benign (Oct 13, 2023)
19-35718020-T-TGGCGGCGGCGGCG		Dystonia 28, childhood-onset • Inborn genetic diseases	Pathogenic (Aug 01, 2023)
19-35718023-C-CGGCGGCGGCG		Dystonia 28, childhood-onset	Pathogenic (Mar 22, 2022)
19-35718026-C-CGGCGGCG			Pathogenic (May 22, 2023)
19-35718031-G-A			Likely benign (Jan 29, 2024)
19-35718040-G-A			Uncertain significance (Jan 26, 2023)
19-35718048-C-T			Likely benign (Jan 03, 2024)
19-35718058-G-A			Uncertain significance (Mar 01, 2023)
19-35718060-C-T			Likely benign (Feb 01, 2023)
19-35718061-T-C		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
19-35718073-C-T			Uncertain significance (Aug 30, 2022)
19-35718078-C-T			Likely benign (Jan 29, 2024)
19-35718082-G-A			Uncertain significance (May 08, 2023)
19-35718097-G-T		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
19-35718098-C-T			Uncertain significance (Feb 14, 2022)
19-35718099-C-CGGCGGG			Uncertain significance (Mar 08, 2022)
19-35718106-G-A			Uncertain significance (Nov 04, 2023)
19-35718110-G-C		Inborn genetic diseases	Uncertain significance (Feb 13, 2024)
19-35718116-G-A			Uncertain significance (Jun 17, 2023)
19-35718118-G-A			Uncertain significance (Mar 10, 2023)
19-35718121-G-C		Inborn genetic diseases	Uncertain significance (Oct 04, 2022)
19-35718126-G-T			Likely benign (Nov 02, 2022)
19-35718131-A-G		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
19-35718132-CG-C		Dystonia 28, childhood-onset	Pathogenic (Mar 06, 2019)

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
1.00	1.98e-16	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

Haploinsufficiency Scores

• pHI: 0.693
• hipred: Y
• hipred_score: 0.572

Essentials

• essential_gene_CRISPR: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kmt2b
• Phenotype: growth/size/body region 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; homeostasis/metabolism phenotype; cellular phenotype; embryo phenotype; liver/biliary system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); normal phenotype; reproductive system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

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)