DROSHA

drosha ribonuclease III, the group of Endoribonucleases

Basic information

Region (hg38): 5:31400494-31532196

Previous symbols: [ "RNASEN" ]

Links

ENSG00000113360 ∙ NCBI:29102 ∙ OMIM:608828 ∙ HGNC:17904 ∙ Uniprot:Q9NRR4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DROSHA gene.

• not_specified (114 variants)
• DROSHA-related_disorder (69 variants)
• not_provided (24 variants)
• Pineoblastoma (7 variants)
• MicroRNA_processor_tumor_predisposition_syndrome (4 variants)
• Hepatoblastoma (2 variants)
• Pyloric_stenosis (1 variants)
• Abnormality_of_neuronal_migration (1 variants)
• Hereditary_breast_ovarian_cancer_syndrome (1 variants)
• DROSHA-related_neurodevelopmental_disorder (1 variants)
• Esophageal_atresia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DROSHA gene is commonly pathogenic or not. These statistics are base on transcript: NM_001382508.1. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	32	6	41
missense	2		140	7	4	153
nonsense	2		6			8
start loss						0
frameshift	4		2			6
splice donor/acceptor (+/-2bp)	2		11			13
Total	10	0	162	39	10

Highest pathogenic variant AF is 0.0000034414215

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DROSHA	protein_coding	protein_coding	ENST00000511367	33	131700

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		124604	0	35	124639	0.000140

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.98	469	783	0.599	0.0000446	9080
Missense in Polyphen		37	168.94	0.21901		1775
Synonymous	0.884	253	272	0.932	0.0000153	2529
Loss of Function	6.45	20	83.7	0.239	0.00000511	922

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000616	0.000610
Ashkenazi Jewish	0.000402	0.000398
East Asian	0.000111	0.000111
Finnish	0.0000929	0.0000928
European (Non-Finnish)	0.000117	0.000115
Middle Eastern	0.000111	0.000111
South Asian	0.000103	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ribonuclease III double-stranded (ds) RNA-specific endoribonuclease that is involved in the initial step of microRNA (miRNA) biogenesis. Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DROSHA cleaves the 3' and 5' strands of a stem-loop in pri-miRNAs (processing center 11 bp from the dsRNA- ssRNA junction) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs. Involved also in pre-rRNA processing. Cleaves double- strand RNA and does not cleave single-strand RNA. Involved in the formation of GW bodies. {ECO:0000269|PubMed:10948199, ECO:0000269|PubMed:14508493, ECO:0000269|PubMed:15531877, ECO:0000269|PubMed:15565168, ECO:0000269|PubMed:15574589, ECO:0000269|PubMed:15589161, ECO:0000269|PubMed:16751099, ECO:0000269|PubMed:16906129, ECO:0000269|PubMed:17159994, ECO:0000269|PubMed:26027739, ECO:0000269|PubMed:26748718}.
• Pathway: Ribosome biogenesis in eukaryotes - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);miRNA Biogenesis;RNA interference;DDX1 as a regulatory component of the Drosha microprocessor;Gene expression (Transcription);Direct p53 effectors;MicroRNA (miRNA) biogenesis;Gene Silencing by RNA (Consensus)

Recessive Scores

• pRec: 0.255

Intolerance Scores

• rvis_EVS: -0.46
• rvis_percentile_EVS: 23.66

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Zebrafish Information Network

• Gene name: drosha
• Affected structure: vasculature
• Phenotype tag: abnormal
• Phenotype quality: increased permeability

Gene ontology

• Biological process: RNA processing;miRNA metabolic process;positive regulation of gene expression;rRNA catabolic process;production of siRNA involved in RNA interference;primary miRNA processing;pre-miRNA processing;ribosome biogenesis;regulation of regulatory T cell differentiation;regulation of inflammatory response;defense response to Gram-negative bacterium;defense response to Gram-positive bacterium;RNA phosphodiester bond hydrolysis, endonucleolytic;regulation of miRNA metabolic process
• Cellular component: nucleus;nucleoplasm;nucleolus;postsynaptic density;microprocessor complex
• Molecular function: lipopolysaccharide binding;RNA binding;double-stranded RNA binding;ribonuclease III activity;protein binding;DEAD/H-box RNA helicase binding;protein homodimerization activity;SMAD binding;metal ion binding;R-SMAD binding;primary miRNA binding