DICER1

Chr 14AD

dicer 1, ribonuclease III

Also known as: DCR1, Dicer, Dicer1e, GLOW, HERNA, K12H4.8-LIKE, MNG1, RMSE2

NCBI Gene: 23405ENSG00000100697UniProt: Q9UPY3OMIM: 606241

The protein functions as a double-stranded RNA endoribonuclease that cleaves precursor microRNAs and long double-stranded RNAs into short interfering RNAs and mature microRNAs, playing a central role in RNA interference and post-transcriptional gene silencing. Mutations cause autosomal dominant DICER1 syndrome, which includes pleuropulmonary blastoma, multinodular goiter with or without Sertoli-Leydig cell tumors, embryonal rhabdomyosarcoma, and GLOW syndrome. This represents a tumor predisposition syndrome with varied oncologic manifestations affecting multiple organ systems.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.174 OMIM phenotypes
Clinical Summary— DICER1
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Gene-Disease Validity (ClinGen)
DICER1-related tumor predisposition · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
6 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.17LOEUF
pLI 1.000
Z-score 7.85
OE 0.09 (0.05–0.17)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
4.23Z-score
OE missense 0.62 (0.58–0.67)
626 obs / 1002.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.09 (0.05–0.17)
0≤0.351.4
Missense OE0.62 (0.58–0.67)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 8 / 87.0Missense obs/exp: 626 / 1002.6Syn Z: -0.11
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveDICER1-related tumor predispositionLOFAD
DN
0.3296th %ile
GOF
0.3987th %ile
LOF
0.70top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.17

Literature Evidence

LOFImportantly, however, the gene has not been reported to undergo homozygous deletion, suggesting that DICER1 is haploinsufficient in human cancer.PMID:19903759

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

DICER1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
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