DROSHA

Chr 5

drosha ribonuclease III

Also known as: ETOHI2, HSA242976, RANSE3L, RN3, RNASE3L, RNASEN

NCBI Gene: 29102ENSG00000113360UniProt: Q9NRR4OMIM: 608828

The protein is a ribonuclease III enzyme that cleaves primary microRNA transcripts in the nucleus as part of the microprocessor complex, catalyzing the initial step of microRNA biogenesis by generating precursor miRNAs. Mutations cause neurodevelopmental disorders with intellectual disability, growth abnormalities, and various congenital malformations, following an autosomal dominant inheritance pattern. The gene is highly constrained against loss-of-function variation (LOEUF 0.347), reflecting its essential role in cellular regulation through microRNA processing.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOEUF 0.35
Clinical Summary— DROSHA
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
39 unique Pathogenic / Likely Pathogenic· 143 VUS of 297 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — DROSHA
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.35LOEUF
pLI 0.093
Z-score 6.45
OE 0.24 (0.17–0.35)
Highly constrained

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

Missense Constraint
3.98Z-score
OE missense 0.60 (0.56–0.65)
469 obs / 782.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.24 (0.17–0.35)
0≤0.351.4
Missense OE0.60 (0.56–0.65)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 20 / 83.7Missense obs/exp: 469 / 782.7Syn Z: 0.88

ClinVar Variant Classifications

297 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic4
VUS143
Likely Benign50
Benign15
35
Pathogenic
4
Likely Pathogenic
143
VUS
50
Likely Benign
15
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
1
26
0
35
Likely Pathogenic
0
0
4
0
4
VUS
4
134
5
0
143
Likely Benign
0
7
11
32
50
Benign
0
5
2
8
15
Total121474840247

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

View in ClinVar →

Protein Context — Lollipop Plot

DROSHA · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Cytoplasmic RNase III Drosha controls lipogenesis by noncanonical regulation of SREBP1.
Nie T et al.·Mol Cell
2026
An intrinsically disordered region of Drosha selectively promotes miRNA biogenesis independent of tissue-specific Microprocessor condensates.
Yang B et al.·Genes Dev
2026
DROSHA, DICER, and damage-induced long ncRNA control BMI1-dependent transcriptional repression at DNA double-strand break.
Esposito F et al.·Cell Rep
2025Open Access
SARS-CoV-2 Infection of Lung Epithelia Leads to an Increase in the Cleavage and Translocation of RNase-III Drosha; Loss of Drosha Is Associated with a Decrease in Viral Replication.
Winters MT et al.·Genes (Basel)
2025Open Access
Non-Canonical Compartmentalization of DROSHA Protein at the Golgi Apparatus: miRNA Biogenesis-Independent Functionality in Human Cancer Cells of Diverse Tissue Origin.
Theotoki EI et al.·Int J Mol Sci
2025Open AccessFunctional
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