L3MBTL3

protein-coding

L3MBTL histone methyl-lysine binding protein 3, the group of MBT domain containing|Sterile alpha motif domain containing

Gene summary

This gene encodes a member of the malignant brain tumor (MBT) family of chromatin interacting transcriptional repressors. Members of this family function as methyl-lysine readers, which recognize methylated lysine residues on histone protein tails, and are associated with the repression of gene expression. The encoded protein may regulate hematopoiesis. Homozygous deletion of this gene has been observed in human patients with medulloblastoma. [provided by RefSeq, Oct 2016]

MANE transcript

NM_032438.4

Inheritance

—

ClinVar variants

U:102B:2

Top phenotype

L3MBTL3-related condition

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr6:130,013,699-130,141,449

External References & Databases

Ensembl (ENSG00000198945)

Transcript & Mutation Effects

hg38 • Region Span ~127.8 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 L3MBTL3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 95

not providedTotal: 4

L3MBTL3-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032438.4. 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	1
missense			99 clinvar	1 clinvar		100
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	102	1	1	104

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 63 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032438.4	RefSeq	NP_115814.1	21	MANE Select
ENST00000361794.7	Ensembl	ENSP00000354526.2	21	MANE Select
NM_001007102.4	RefSeq	NP_001007103.1	20	Standard
NM_001346550.2	RefSeq	NP_001333479.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

chromatin organization
regulation of transcription, DNA-templated
macrophage differentiation
granulocyte differentiation
erythrocyte maturation

Molecular Function

molecular_function
DNA-binding transcription factor activity
protein binding
zinc ion binding

Cellular Component

nucleus
nucleolus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000529410
Coding exons: 21
Length: 127751
Individuals with no LoFs: 125415
Homozygous LoFs: 0
Heterozygous LoFs: 330
Defined: 125745
p: 0.00131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.64	333	428	0.777	0.0000227	5177
Missense (PolyPhen)		100	174.14	0.57426		2164
Synonymous	-0.532	160	152	1.05	0.00000876	1390
Loss of Function	5.30	6	44.0	0.137	0.00000203	568

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0041	0.0039	notable
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0.00050	0.00050	rare
East Asian	0.0018	0.0018	notable
Finnish	0.0036	0.0035	notable
European (Non-Finnish)	0.0012	0.0011	notable
South Asian	0.000033	0.000033	rare
Other	0.0020	0.0020	notable

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. Required for normal maturation of myeloid progenitor cells (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.0984

Intolerance Scores

LoFtool: 0.400
RVIS EVS: -0.78
RVIS percentile EVS: 12.97

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.939

Gene Damage Prediction

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