DICER1
dicer 1, ribonuclease III, the group of RNA helicases|Endoribonucleases|RISC loading complex|MicroRNA protein coding host genes
Basic information
Region (hg38): 14:95086227-95158010
Previous symbols: [ "MNG1" ]
Links
Phenotypes
GenCC
Source:
- pleuropulmonary blastoma (Strong), mode of inheritance: AD
- DICER1 syndrome (Supportive), mode of inheritance: AD
- goiter, multinodular 1, with or without Sertoli-Leydig cell tumors (Definitive), mode of inheritance: AD
- pleuropulmonary blastoma (Definitive), mode of inheritance: AD
- global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome (Limited), mode of inheritance: Unknown
- DICER1-related tumor predisposition (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| DICER1 syndrome | AD | Oncologic | As individuals are at risk for a variety of neoplasms, surveillance and early diagnosis allowing early treatment of specific tumor types could potentially be beneficial | Oncologic | 6261577; 799599; 9345104; 9295070; 18570301; 19556464; 21036787; 21266384; 21882293; 24761742 |
| Individuals are at risk for multiple malignancy types |
ClinVar
This is a list of variants' phenotypes submitted to
- DICER1-related tumor predisposition (4609 variants)
- Hereditary cancer-predisposing syndrome (2926 variants)
- not provided (517 variants)
- not specified (288 variants)
- Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome (190 variants)
- Pleuropulmonary blastoma (69 variants)
- DICER1-related condition (25 variants)
- Euthyroid goiter (19 variants)
- Ovarian cancer (12 variants)
- Inborn genetic diseases (6 variants)
- Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome;Euthyroid goiter;Rhabdomyosarcoma, embryonal, 2;Pleuropulmonary blastoma (6 variants)
- Pineoblastoma (6 variants)
- Rhabdomyosarcoma, embryonal, 2 (6 variants)
- Euthyroid goiter;Rhabdomyosarcoma, embryonal, 2;DICER1-related tumor predisposition (3 variants)
- Pleuropulmonary blastoma;Euthyroid goiter;Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome;Rhabdomyosarcoma, embryonal, 2 (3 variants)
- DICER1-related tumor predisposition;Euthyroid goiter;Rhabdomyosarcoma, embryonal, 2 (3 variants)
- Breast neoplasm (3 variants)
- Rhabdomyosarcoma, embryonal, 2;Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome;Euthyroid goiter;Pleuropulmonary blastoma (2 variants)
- DICER1-related tumor predisposition;Rhabdomyosarcoma, embryonal, 2;Euthyroid goiter (2 variants)
- Rhabdomyosarcoma (2 variants)
- Rhabdomyosarcoma, embryonal, 2;DICER1-related tumor predisposition;Euthyroid goiter (2 variants)
- Euthyroid goiter;Rhabdomyosarcoma, embryonal, 2;Pleuropulmonary blastoma;Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome (1 variants)
- Malignant tumor of breast (1 variants)
- Euthyroid goiter;Pleuropulmonary blastoma (1 variants)
- Diffuse midline glioma, H3 K27-altered (1 variants)
- Rhabdomyosarcoma, embryonal, 2;Euthyroid goiter;DICER1-related tumor predisposition (1 variants)
- Anophthalmia-microphthalmia syndrome (1 variants)
- Pleuropulmonary blastoma;Rhabdomyosarcoma, embryonal, 2;Euthyroid goiter;Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome (1 variants)
- Vertebral anomalies and variable endocrine and T-cell dysfunction (1 variants)
- Pleuropulmonary blastoma;Euthyroid goiter;Rhabdomyosarcoma, embryonal, 2;Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome (1 variants)
- Medulloblastoma (1 variants)
- Supratentorial primitive neuroectodermal tumor (1 variants)
- Euthyroid goiter;Pleuropulmonary blastoma;Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome;Rhabdomyosarcoma, embryonal, 2 (1 variants)
- Rhabdomyosarcoma, embryonal, 2;Pleuropulmonary blastoma;Euthyroid goiter;Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DICER1 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 | 23 | 1296 | 1326 | |||
| missense | 29 | 14 | 2659 | 54 | 2764 | |
| nonsense | 155 | 19 | 10 | 185 | ||
| start loss | 1 | |||||
| frameshift | 291 | 35 | 332 | |||
| inframe indel | 51 | 60 | ||||
| splice donor/acceptor (+/-2bp) | 31 | 54 | 86 | |||
| splice region ? | 3 | 127 | 133 | 10 | 273 | |
| non coding ? | 83 | 443 | 93 | 623 | ||
| Total | 511 | 130 | 2834 | 1795 | 107 |
Highest pathogenic variant AF is 0.00000658
Variants in DICER1
This is a list of pathogenic ClinVar variants found in the DICER1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 14-95086238-A-G | DICER1-related tumor predisposition | Uncertain significance (Jan 13, 2018) | ||
| 14-95086257-A-C | DICER1-related tumor predisposition | Uncertain significance (Jan 12, 2018) | ||
| 14-95086370-T-C | DICER1-related tumor predisposition | Uncertain significance (Jan 13, 2018) | ||
| 14-95086459-C-T | DICER1-related tumor predisposition | Benign (Jan 13, 2018) | ||
| 14-95086462-T-C | DICER1-related tumor predisposition | Uncertain significance (Jan 12, 2018) | ||
| 14-95086493-C-T | DICER1-related tumor predisposition | Uncertain significance (Jan 12, 2018) | ||
| 14-95086532-G-T | DICER1-related tumor predisposition | Uncertain significance (Jan 13, 2018) | ||
| 14-95086612-G-A | DICER1-related tumor predisposition | Benign (Jan 12, 2018) | ||
| 14-95086682-T-C | DICER1-related tumor predisposition | Uncertain significance (Jan 13, 2018) | ||
| 14-95086762-A-C | DICER1-related tumor predisposition | Benign (Jan 13, 2018) | ||
| 14-95086919-C-A | DICER1-related tumor predisposition | Uncertain significance (Jan 13, 2018) | ||
| 14-95086920-A-G | DICER1-related tumor predisposition | Uncertain significance (Jan 13, 2018) | ||
| 14-95087025-A-G | DICER1-related tumor predisposition | Benign (Jan 12, 2018) | ||
| 14-95087084-G-A | DICER1-related tumor predisposition | Uncertain significance (Apr 27, 2017) | ||
| 14-95087132-G-A | DICER1-related tumor predisposition | Uncertain significance (Jan 13, 2018) | ||
| 14-95087157-G-A | DICER1-related tumor predisposition | Benign (Jan 12, 2018) | ||
| 14-95087186-C-A | DICER1-related tumor predisposition | Benign (Jan 13, 2018) | ||
| 14-95087216-G-T | DICER1-related tumor predisposition | Uncertain significance (Jan 12, 2018) | ||
| 14-95087264-C-A | DICER1-related tumor predisposition | Benign (Jan 13, 2018) | ||
| 14-95087313-C-A | DICER1-related tumor predisposition | Benign (Jan 13, 2018) | ||
| 14-95087323-C-T | DICER1-related tumor predisposition | Uncertain significance (Jan 13, 2018) | ||
| 14-95087459-C-G | DICER1-related tumor predisposition | Uncertain significance (Jan 12, 2018) | ||
| 14-95087474-T-C | DICER1-related tumor predisposition | Uncertain significance (Jan 13, 2018) | ||
| 14-95087533-AC-A | Pleuropulmonary blastoma | Uncertain significance (Jun 14, 2016) | ||
| 14-95087618-T-A | DICER1-related tumor predisposition | Uncertain significance (Jan 13, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| DICER1 | protein_coding | protein_coding | ENST00000526495 | 26 | 71783 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 7.17e-9 | 125732 | 0 | 16 | 125748 | 0.0000636 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 4.23 | 626 | 1.00e+3 | 0.624 | 0.0000543 | 12679 |
| Missense in Polyphen | 199 | 489.05 | 0.40691 | 6199 | ||
| Synonymous | -0.106 | 370 | 367 | 1.01 | 0.0000208 | 3636 |
| Loss of Function | 7.85 | 8 | 87.0 | 0.0920 | 0.00000491 | 1130 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000579 | 0.0000579 |
| Ashkenazi Jewish | 0.0000992 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.0000616 | 0.0000615 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.000131 | 0.000131 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: 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. {ECO:0000269|PubMed:15242644, ECO:0000269|PubMed:15973356, ECO:0000269|PubMed:16142218, ECO:0000269|PubMed:16271387, ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:16357216, ECO:0000269|PubMed:16424907, ECO:0000269|PubMed:17452327, ECO:0000269|PubMed:18178619, ECO:0000269|PubMed:19219043}.;
- Disease
- DISEASE: Pleuropulmonary blastoma (PPB) [MIM:601200]: A rare pediatric intrathoracic neoplasm. The tumor arises from the lung, pleura, or both, and appears to be purely mesenchymal in phenotype. It lacks malignant epithelial elements, a feature that distinguishes it from the classic adult-type pulmonary blastoma. It arises during fetal lung development and is often part of an inherited cancer syndrome. The tumor contain both epithelial and mesenchymal cells. Early in tumorigenesis, cysts form in lung airspaces, and these cysts are lined with benign-appearing epithelium. Mesenchymal cells susceptible to malignant transformation reside within the cyst walls and form a dense layer beneath the epithelial lining. In a subset of patients, overgrowth of the mesenchymal cells produces a sarcoma, a transition that is associated with a poorer prognosis. Some patients have multilocular cystic nephroma, a benign kidney tumor. {ECO:0000269|PubMed:19556464}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Goiter multinodular 1, with or without Sertoli-Leydig cell tumors (MNG1) [MIM:138800]: A common disorder characterized by nodular overgrowth of the thyroid gland. Some individuals may also develop Sertoli-Leydig cell tumors, usually of the ovary. {ECO:0000269|PubMed:21205968}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Rhabdomyosarcoma, embryonal, 2 (RMSE2) [MIM:180295]: A form of rhabdomyosarcoma, a highly malignant tumor of striated muscle derived from primitive mesenchymal cells and exhibiting differentiation along rhabdomyoblastic lines. Rhabdomyosarcoma is one of the most frequently occurring soft tissue sarcomas and the most common in children. It occurs in four forms: alveolar, pleomorphic, embryonal and botryoidal rhabdomyosarcomas. {ECO:0000269|PubMed:21882293}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=DICER1 mutations have been found in uterine cervix embryonal rhabdomyosarcoma, primitive neuroectodermal tumor, Wilms tumor, pulmonary sequestration and juvenile intestinal polyp (PubMed:21882293). Somatic missense mutations affecting the RNase IIIb domain of DICER1 are common in non-epithelial ovarian tumors. These mutations do not abolish DICER1 function but alter it in specific cell types, a novel mechanism through which perturbation of microRNA processing may be oncogenic (PubMed:22187960). {ECO:0000269|PubMed:21882293, ECO:0000269|PubMed:22187960}.;
- Pathway
- MicroRNAs in cancer - Homo sapiens (human);miRNA Biogenesis;RNA interference;Hypoxia-mediated EMT and Stemness;mRNA Processing;Gene expression (Transcription);dicer pathway;Validated transcriptional targets of TAp63 isoforms;MicroRNA (miRNA) biogenesis;Small interfering RNA (siRNA) biogenesis;Gene Silencing by RNA
(Consensus)
Recessive Scores
- pRec
- 0.495
Intolerance Scores
- loftool
- 0.233
- rvis_EVS
- -1.52
- rvis_percentile_EVS
- 3.44
Haploinsufficiency Scores
- pHI
- 0.417
- hipred
- Y
- hipred_score
- 0.704
- ghis
- 0.613
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.924
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Dicer1
- Phenotype
- embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; normal 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); reproductive system 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); neoplasm; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype; skeleton phenotype; renal/urinary system 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; muscle phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- dicer1
- Affected structure
- trigeminal sensory neuron
- Phenotype tag
- abnormal
- Phenotype quality
- mislocalised
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;apoptotic DNA fragmentation;miRNA metabolic process;negative regulation of Schwann cell proliferation;positive regulation of Schwann cell differentiation;nerve development;production of siRNA involved in RNA interference;targeting of mRNA for destruction involved in RNA interference;pre-miRNA processing;positive regulation of myelination;peripheral nervous system myelin formation;negative regulation of tumor necrosis factor production;conversion of ds siRNA to ss siRNA involved in RNA interference;siRNA loading onto RISC involved in RNA interference;production of miRNAs involved in gene silencing by miRNA;miRNA loading onto RISC involved in gene silencing by miRNA;conversion of ds siRNA to ss siRNA;NIK/NF-kappaB signaling;neuron projection morphogenesis;RNA phosphodiester bond hydrolysis, endonucleolytic
- Cellular component
- nucleus;cytoplasm;endoplasmic reticulum-Golgi intermediate compartment;cytosol;RISC complex;dendrite;growth cone;ARC complex;micro-ribonucleoprotein complex;extracellular exosome;RISC-loading complex
- Molecular function
- DNA binding;double-stranded RNA binding;helicase activity;endoribonuclease activity;ribonuclease III activity;deoxyribonuclease I activity;protein binding;ATP binding;protein domain specific binding;siRNA binding;metal ion binding;pre-miRNA binding