L3MBTL4

protein-coding

L3MBTL histone methyl-lysine binding protein 4, the group of MicroRNA protein coding host genes|MBT domain containing|Sterile alpha motif domain containing

Gene summary

Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of DNA-templated transcription. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001330559.2

Inheritance

—

ClinVar variants

U:94B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr18:5,954,706-6,415,237

External References & Databases

Ensembl (ENSG00000154655)

Transcript & Mutation Effects

hg38 • Region Span ~460.5 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 L3MBTL4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 92

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001330559.2. 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			1 clinvar	2 clinvar		3
missense			91 clinvar	2 clinvar		93
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	94	4	0	98

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 84 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001330559.2	RefSeq	NP_001317488.1	17	MANE Select
ENST00000317931.12	Ensembl	ENSP00000318543.7	17	MANE Select
NM_001365765.2	RefSeq	NP_001352694.1	17	Standard
NM_001365766.2	RefSeq	NP_001352695.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

chromatin organization
regulation of transcription, DNA-templated

Molecular Function

DNA-binding transcription factor activity
protein binding
zinc ion binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000284898
Coding exons: 18
Length: 460532
Individuals with no LoFs: 125698
Homozygous LoFs: 0
Heterozygous LoFs: 50
Defined: 125748
p: 0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.397	320	341	0.939	0.0000186	4099
Missense (PolyPhen)		97	124.41	0.77968		1521
Synonymous	-0.728	133	123	1.08	0.00000713	1115
Loss of Function	2.29	23	38.3	0.600	0.00000194	453

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00028	0.00027	rare
South Asian	0.00021	0.00020	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 (By similarity). {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.745
RVIS EVS: -0.95
RVIS percentile EVS: 9.21

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.296

Gene Damage Prediction

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