EHMT2

protein-coding

euchromatic histone lysine methyltransferase 2, the group of Lysine methyltransferases|Ankyrin repeat domain containing|SET domain containing

Gene summary

This gene encodes a methyltransferase that methylates lysine residues of histone H3. Methylation of H3 at lysine 9 by this protein results in recruitment of additional epigenetic regulators and repression of transcription. This gene was initially thought to be two different genes, NG36 and G9a, adjacent to each other in the HLA locus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Previous symbols:

C6orf30
BAT8

MANE transcript

NM_006709.5

Inheritance

ClinVar variants

P:5U:146B:12

Top phenotype

Kleefstra-like syndrome

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr6:31,879,759-31,897,698

External References & Databases

Ensembl (ENSG00000204371)

Transcript & Mutation Effects

hg38 • Region Span ~17.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EHMT2 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 128

not providedTotal: 11

Kleefstra-like syndromeTotal: 7

Syndromic neurodevelopmental disorderTotal: 3

EHMT2-related Kleefstra-like syndromeTotal: 1

EHMT2-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006709.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			7 clinvar	5 clinvar	4 clinvar	16
missense	5 clinvar		132 clinvar	2 clinvar	1 clinvar	140
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	5	0	146	7	5	163

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 83 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006709.5	RefSeq	NP_006700.3	28	MANE Select
ENST00000375537.9	Ensembl	ENSP00000364687.4	28	MANE Select
NM_001289413.2	RefSeq	NP_001276342.1	26	Standard
NM_001318833.2	RefSeq	NP_001305762.1	24	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ehmt2	Danio rerio	Structure: retina Quality: increased occurrence abnormal

Gene / Model

Organism

Observed Phenotype

ehmt2

Danio rerio

Structure: retina

Quality: increased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysine degradation - Homo sapiens (human)
Longevity regulating pathway - Homo sapiens (human)
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase
Histone Modifications

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of DNA replication
DNA methylation
cellular response to starvation
histone methylation

Molecular Function

p53 binding
protein binding
zinc ion binding
protein-lysine N-methyltransferase activity
histone-lysine N-methyltransferase activity

Cellular Component

nuclear chromatin
nucleus
nucleoplasm
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375537
Coding exons: 28
Length: 17929
Individuals with no LoFs: 125708
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125748
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.71	483	773	0.624	0.0000505	7796
Missense (PolyPhen)		177	367.7	0.48138		3761
Synonymous	1.41	277	309	0.898	0.0000199	2462
Loss of Function	5.19	20	65.2	0.307	0.00000373	713

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00079	0.00074	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000055	0.000054	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00016	0.00015	rare
South Asian	0.00021	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys- 373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself. {ECO:0000269|PubMed:11316813, ECO:0000269|PubMed:18438403, ECO:0000269|PubMed:20084102, ECO:0000269|PubMed:20118233, ECO:0000269|PubMed:22387026, ECO:0000269|PubMed:8457211}.;

Recessive Scores

pRec: 0.120

Intolerance Scores

LoFtool: 0.626
RVIS EVS: -0.88
RVIS percentile EVS: 10.5

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.990

Gene Damage Prediction

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