L3MBTL4

Chr 18

L3MBTL histone methyl-lysine binding protein 4

Also known as: HsT1031

NCBI Gene: 91133ENSG00000154655UniProt: Q8NA19

The L3MBTL4 protein is a putative Polycomb group protein that binds chromatin and histones to maintain transcriptional repression of target genes. This gene is extremely intolerant to loss-of-function variants (pLI ~1.0), but no definitive human disease associations have been established in the provided data. Further research is needed to determine the clinical significance of L3MBTL4 variants in pediatric patients.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
117
P/LP submissions
0%
P/LP missense
0.85
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— L3MBTL4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
112 unique Pathogenic / Likely Pathogenic· 99 VUS of 239 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.85LOEUF
pLI 0.000
Z-score 2.29
OE 0.60 (0.43–0.85)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.40Z-score
OE missense 0.94 (0.86–1.03)
320 obs / 340.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.60 (0.43–0.85)
0≤0.351.4
Missense OE0.94 (0.86–1.03)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 23 / 38.3Missense obs/exp: 320 / 340.6Syn Z: -0.73
DN
0.6549th %ile
GOF
0.6443th %ile
LOF
0.3844th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

239 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic111
Likely Pathogenic1
VUS99
Likely Benign5
Conflicting1
111
Pathogenic
1
Likely Pathogenic
99
VUS
5
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
111
0
111
Likely Pathogenic
0
0
1
0
1
VUS
0
87
12
0
99
Likely Benign
0
2
1
2
5
Benign
0
0
0
0
0
Conflicting
—1
Total0891252217

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

L3MBTL4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients