DNMT3L
Chr 21DNA methyltransferase 3 like
DNMT3L encodes a catalytically inactive regulatory factor that activates DNA methyltransferases DNMT3A and DNMT3B, playing essential roles in establishing genomic imprints and methylating retrotransposons in germ cells. The gene is not highly constrained against loss-of-function variants (pLI ~0, LOEUF 1.3), and mutations cause maternal-effect lethal overgrowth syndrome, characterized by fetal overgrowth and pregnancy complications. This condition follows an autosomal recessive inheritance pattern affecting maternal oocyte function.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
ClinVar Variant Classifications
190 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 82 | 0 | 82 |
Likely Pathogenic | 0 | 0 | 5 | 0 | 5 |
VUS | 0 | 65 | 16 | 0 | 81 |
Likely Benign | 0 | 5 | 1 | 1 | 7 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 1 | |||
| Total | 0 | 70 | 104 | 1 | 176 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DNMT3L · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools