L3MBTL2

protein-coding

L3MBTL histone methyl-lysine binding protein 2, the group of MBT domain containing

Gene summary

Enables histone H4K20me1 reader activity; histone H4K20me2 reader activity; and histone binding activity. Predicted to be involved in negative regulation of DNA-templated transcription. Predicted to act upstream of or within several processes, including ectoderm development; stem cell differentiation; and stem cell proliferation. Located in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_031488.5

Inheritance

—

ClinVar variants

P:1U:87B:6

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr22:41,205,282-41,231,271

External References & Databases

Ensembl (ENSG00000100395)

Transcript & Mutation Effects

hg38 • Region Span ~26.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to L3MBTL2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 85

not providedTotal: 4

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Non-obstructive azoospermiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031488.5. 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				2 clinvar	2 clinvar	4
missense	1 clinvar		83 clinvar	1 clinvar	1 clinvar	86
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	1	0	87	3	3	94

Highest pathogenic variant AF is 0.000013630646

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031488.5	RefSeq	NP_113676.2	17	MANE Select
ENST00000216237.10	Ensembl	ENSP00000216237.5	17	MANE Select
ENST00000449635.5	Ensembl	ENSP00000399405.1	6	Standard
ENST00000450939.1	Ensembl	ENSP00000403767.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
Transcriptional Regulation by E2F6
Generic Transcription Pathway
SUMOylation of chromatin organization proteins
Post-translational protein modification

Biological Process

chromatin organization
regulation of transcription, DNA-templated
negative regulation of G0 to G1 transition

Molecular Function

protein binding
zinc ion binding
methylated histone binding
histone binding

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000216237
Coding exons: 17
Length: 26067
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	1.92	322	435	0.740	0.0000263	4639
Missense (PolyPhen)		75	125.11	0.59946		1347
Synonymous	0.137	174	176	0.987	0.0000119	1338
Loss of Function	2.99	20	40.6	0.493	0.00000227	430

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000097	0.000092	rare
European (Non-Finnish)	0.00017	0.00016	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Putative Polycomb group (PcG) protein. PcG proteins maintain the transcriptionally repressive state of genes, probably via a modification of chromatin, rendering it heritably changed in its expressibility. Its association with a chromatin-remodeling complex suggests that it may contribute to prevent expression of genes that trigger the cell into mitosis. Binds to monomethylated and dimethylated 'Lys-20' on histone H4. Binds histone H3 peptides that are monomethylated or dimethylated on 'Lys-4', 'Lys-9' or 'Lys-27'. {ECO:0000269|PubMed:19233876}.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.641
RVIS EVS: -1.17
RVIS percentile EVS: 6.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.591

Gene Damage Prediction

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