DROSHA

drosha ribonuclease III, the group of Endoribonucleases

Basic information

Region (hg38): 5:31400493-31532196

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.

• Inborn genetic diseases (20 variants)
• not provided (17 variants)
• DROSHA-related condition (8 variants)
• DROSHA-related neurodevelopmental disorder (1 variants)
• Hereditary breast ovarian cancer syndrome (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	5	8
missense			31	2	1	34
nonsense	1					1
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				1	1	2
Total	1	0	32	6	7

Variants in DROSHA

This is a list of pathogenic ClinVar variants found in the DROSHA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-31401440-T-C			Uncertain significance (Aug 04, 2022)
5-31401525-G-A		DROSHA-related disorder	Likely benign (Jan 10, 2022)
5-31405728-TAAATA-T		DROSHA-related disorder	Likely benign (Dec 27, 2022)
5-31406873-T-G			Benign (Dec 31, 2019)
5-31406952-G-A		DROSHA-related disorder	Likely benign (May 20, 2022)
5-31409059-T-C		not specified	Uncertain significance (Oct 25, 2023)
5-31409103-G-A		DROSHA-related disorder	Likely benign (Jul 05, 2022)
5-31409129-G-A		not specified	Uncertain significance (Aug 17, 2022)
5-31409145-A-G		DROSHA-related disorder	Benign (Oct 30, 2019)
5-31410757-T-C		DROSHA-related neurodevelopmental disorder	Uncertain significance (Aug 19, 2019)
5-31410759-C-T		DROSHA-related disorder	Likely benign (Feb 17, 2022)
5-31410780-C-T		DROSHA-related disorder	Likely benign (Sep 14, 2023)
5-31410786-A-G		DROSHA-related disorder	Likely benign (Jun 03, 2022)
5-31410816-G-A		DROSHA-related disorder	Benign (Dec 31, 2019)
5-31410840-C-T		DROSHA-related disorder	Likely benign (Dec 13, 2023)
5-31410843-T-C		DROSHA-related disorder	Likely benign (Sep 20, 2022)
5-31422900-T-C		DROSHA-related disorder	Benign (Oct 30, 2019)
5-31424463-G-A		DROSHA-related disorder	Likely benign (Jun 21, 2022)
5-31424470-T-G		Hepatoblastoma	Uncertain significance (-)
5-31429466-T-C		DROSHA-related disorder	Benign (Dec 31, 2019)
5-31429495-G-A		not specified	Uncertain significance (Jul 25, 2023)
5-31429522-G-A		DROSHA-related disorder	Likely benign (Aug 04, 2021)
5-31429541-A-T			Likely benign (Apr 10, 2018)
5-31431620-G-A		not specified	Uncertain significance (Oct 26, 2022)
5-31435780-A-G		DROSHA-related disorder	Benign (Dec 31, 2019)

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
0.0932	0.907	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

Haploinsufficiency Scores

• pHI: 0.609
• hipred: Y
• hipred_score: 0.652
• ghis: 0.612

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

Mouse Genome Informatics

• Gene name: Drosha
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; muscle phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; immune system phenotype; digestive/alimentary phenotype

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