L3MBTL1
protein-codingL3MBTL histone methyl-lysine binding protein 1, the group of Zinc fingers C2HC-type|MBT domain containing|Sterile alpha motif domain containing
Gene summary
This gene represents a polycomb group gene. The encoded protein functions to regulate gene activity, likely via chromatin modification. The encoded protein may also be necessary for mitosis. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Sep 2010]
- L3MBTL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~61.5 kbGenCC 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 L3MBTL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001377303.1. 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 | 2 | 3 | |||
| missense | 120 | 10 | 1 | 131 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 1 | 125 | 12 | 1 | 139 |
Highest pathogenic variant AF is 0.0000043403047
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001364232.1 | 21 | MANE Select | |
| Ensembl | ENSP00000398516.2 | 21 | MANE Select | |
| RefSeq | NP_001364235.1 | 20 | Standard | |
| RefSeq | NP_001364236.1 | 19 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gene expression (Transcription)
- Generic Transcription Pathway
- RNA Polymerase II Transcription
- Regulation of TP53 Activity through Methylation
- Regulation of TP53 Activity
Biological Process
- chromatin organization
- regulation of mitotic nuclear division
- hemopoiesis
- regulation of megakaryocyte differentiation
- negative regulation of transcription, DNA-templated
Molecular Function
- chromatin binding
- DNA-binding transcription factor activity
- protein binding
- zinc ion binding
- nucleosome binding
Cellular Component
- chromatin
- condensed chromosome
- nucleus
- nucleoplasm
- nucleolus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000427442
- Coding exons
- 21
- Length
- 43271
- Individuals with no LoFs
- 125609
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 139
- Defined
- 125748
- p
- 0.000553
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.00 | 447 | 511 | 0.875 | 0.0000297 | 5470 |
| Missense (PolyPhen) | 110 | 143.1 | 0.7687 | 1612 | ||
| Synonymous | 1.16 | 189 | 210 | 0.898 | 0.0000137 | 1631 |
| Loss of Function | 2.80 | 27 | 47.9 | 0.564 | 0.00000248 | 496 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00068 | 0.00068 | rare |
| Latino/Admixed American | 0.00027 | 0.00026 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.0012 | 0.0012 | notable |
| European (Non-Finnish) | 0.00055 | 0.00054 | rare |
| South Asian | 0.00099 | 0.00098 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Polycomb group (PcG) protein that specifically recognizes and binds mono- and dimethyllysine residues on target proteins, therey acting as a 'reader' of a network of post- translational modifications. PcG proteins maintain the transcriptionally repressive state of genes: acts as a chromatin compaction factor by recognizing and binding mono- and dimethylated histone H1b/HIST1H1E at 'Lys-26' (H1bK26me1 and H1bK26me2) and histone H4 at 'Lys-20' (H4K20me1 and H4K20me2), leading to condense chromatin and repress transcription. Recognizes and binds p53/TP53 monomethylated at 'Lys-382', leading to repress p53/TP53-target genes. Also recognizes and binds RB1/RB monomethylated at 'Lys-860'. Participates in the ETV6-mediated repression. Probably plays a role in cell proliferation. Overexpression induces multinucleated cells, suggesting that it is required to accomplish normal mitosis. {ECO:0000269|PubMed:17540172, ECO:0000269|PubMed:18408754, ECO:0000269|PubMed:20870719, ECO:0000269|PubMed:20870725}.;
Recessive Scores
- pRec
- 0.103
Intolerance Scores
- RVIS EVS
- 0.03
- RVIS percentile EVS
- 55.79
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |