DICER1

Chr 14AD

dicer 1, ribonuclease III

ENSG00000100697UniProt: Q9UPY3

Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing. Cleaves naturally occurring long dsRNAs and short hairpin pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three nucleotides with 3' overhang of two nucleotides, producing respectively short interfering RNAs (siRNA) and mature microRNAs. SiRNAs and miRNAs serve as guide to direct the RNA-induced silencing complex (RISC) to complementary RNAs to degrade them or prevent their translation. Gene silencing mediated by siRNAs, also called RNA interference, controls the elimination of transcripts from mobile and repetitive DNA elements of the genome but also the degradation of exogenous RNA of viral origin for instance. The miRNA pathway on the other side is a mean to specifically regulate the expression of target genes

Primary Disease Associations & Inheritance

GLOW syndrome, somatic mosaicMIM #618272
Goiter, multinodular 1, with or without Sertoli-Leydig cell tumorsMIM #138800
AD
Pleuropulmonary blastomaMIM #601200
AD
Rhabdomyosarcoma, embryonal, 2MIM #180295
UniProtGoiter multinodular 1, with or without Sertoli-Leydig cell tumors
UniProtGlobal developmental delay, lung cysts, overgrowth, and Wilms tumor
0
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
6
Active trials
Clinical Summary— DICER1
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Gene-Disease Validity (ClinGen)
DICER1-related tumor predisposition · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.09 (0.05–0.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.62 (0.58–0.67)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 8 / 87.0Missense obs/exp: 626 / 1002.6Syn Z: -0.11

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.

Gene2Phenotype Curations

DICER1-related tumor predisposition

definitive
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Cancer
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

GLOW syndrome, somatic mosaic

MIM #618272

Molecular basis of disorder known

Goiter, multinodular 1, with or without Sertoli-Leydig cell tumors

MIM #138800

Molecular basis of disorder known

Autosomal dominant

Pleuropulmonary blastoma

MIM #601200

Molecular basis of disorder known

Autosomal dominant

Rhabdomyosarcoma, embryonal, 2

MIM #180295

Molecular basis of disorder known

📖
GeneReview available — DICER1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Overview of the 2022 WHO Classification of Thyroid Neoplasms.
Baloch ZW et al.·Endocr Pathol
2022Review
DICER1 and Associated Conditions: Identification of At-risk Individuals and Recommended Surveillance Strategies.
Schultz KAP et al.·Clin Cancer Res
2018Review
Frequency of Pathogenic Germline Variants in Cancer-Susceptibility Genes in the Childhood Cancer Survivor Study.
Kim J et al.·JNCI Cancer Spectr
2021
Androgen-Secreting Ovarian Tumors.
Macut D et al.·Front Horm Res
2019Review
DICER1-Related Tumor Predisposition: Identification of At-risk Individuals and Recommended Surveillance Strategies.
Schultz KAP et al.·Clin Cancer Res
2024
Uterine sarcomas and rare uterine mesenchymal tumors with malignant potential. Diagnostic guidelines of the French Sarcoma Group and the Rare Gynecological Tumors Group.
Croce S et al.·Gynecol Oncol
2022Review
Genomic characterization of DICER1-associated neoplasms uncovers molecular classes.
Kommoss FKF et al.·Nat Commun
2023
The Histological Spectrum of DICER1-Associated Neoplasms.
Capozzi A et al.·Pediatr Dev Pathol
2025Review
DICER1 in pediatric and adult cancer predisposition populations: Prevalence, phenotypes, and mosaicism.
Salvador L et al.·Genet Med
2025
Rare Hereditary Gynecological Cancer Syndromes.
Watanabe T et al.·Int J Mol Sci
2022Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Ovarian Sex-cord Stromal TumorTesticular Stromal TumorsOvarian Small Cell Carcinoma

International Ovarian & Testicular Stromal Tumor Registry

RECRUITING
NCT01970696Children's Hospitals and Clinics of MinnesotaStarted 2011-12-08
Pleuropulmonary BlastomaSertoli-Leydig Cell TumorDICER1 Syndrome

International PPB/DICER1 Registry

RECRUITING
NCT03382158Children's Hospitals and Clinics of MinnesotaStarted 2016-12-06
Neuroendocrine NeoplasmNeuroendocrine Neoplasm of Gastrointestinal TractNeuroendocrine Neoplasm of Lung

Genetic Bases of Neuroendocrine Neoplasms in Mexican Patients

RECRUITING
NCT06523582Universidad Nacional Autonoma de MexicoStarted 2022-08-03
Acute LeukemiaAdenomatous PolyposisAdrenocortical Carcinoma

Familial Investigations of Childhood Cancer Predisposition

RECRUITING
NCT03050268St. Jude Children's Research HospitalStarted 2017-04-06
Pleuropulmonary BlastomaCystic NephromaOvarian Sertoli-Leydig Cell Tumors

DICER1-related Pleuropulmonary Blastoma Cancer Predisposition Syndrome: A Natural History Study

RECRUITING
NCT01247597National Cancer Institute (NCI)Started 2011-02-13
MelanomaLi-Fraumeni SyndromePulmonary Blastoma

Clinical Genetics Branch Eligibility Screening Survey

NOT YET RECRUITING
NCT07005297National Cancer Institute (NCI)Started 2026-03-16

External Resources

Links to major genomics databases and tools