DGCR8

DGCR8 microprocessor complex subunit, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 22:20080220-20111877

Previous symbols: [ "C22orf12" ]

Links

ENSG00000128191 ∙ NCBI:54487 ∙ OMIM:609030 ∙ HGNC:2847 ∙ Uniprot:Q8WYQ5 ∙ 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 DGCR8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DGCR8 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				18	4	22
missense			33	3		36
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				1	1	2
Total	0	0	34	22	5

Variants in DGCR8

This is a list of pathogenic ClinVar variants found in the DGCR8 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-20085996-G-A			Likely benign (Jun 13, 2018)
22-20086006-G-A		DGCR8-related disorder • not specified	Conflicting classifications of pathogenicity (Aug 08, 2023)
22-20086037-G-A		not specified	Uncertain significance (Apr 25, 2023)
22-20086040-C-G		not specified	Uncertain significance (Sep 16, 2021)
22-20086041-C-T		DGCR8-related disorder	Likely benign (Mar 23, 2021)
22-20086049-C-T		not specified	Uncertain significance (Nov 02, 2023)
22-20086057-C-T		not specified	Uncertain significance (Jul 25, 2023)
22-20086150-G-A		not specified	Uncertain significance (Apr 09, 2024)
22-20086160-C-G		not specified	Uncertain significance (May 15, 2023)
22-20086172-A-G		not specified	Uncertain significance (Jun 06, 2023)
22-20086214-G-A		not specified	Uncertain significance (Apr 25, 2023)
22-20086251-G-A			Likely benign (Dec 31, 2019)
22-20086269-A-G			Likely benign (Jun 27, 2018)
22-20086301-A-G		not specified	Uncertain significance (Jun 06, 2023)
22-20086338-C-T			Likely benign (Nov 13, 2018)
22-20086370-T-C		not specified	Uncertain significance (Jun 22, 2024)
22-20086392-C-T			Likely benign (May 04, 2018)
22-20086401-G-A			Likely benign (Aug 05, 2018)
22-20086407-C-T			Benign (Dec 31, 2019)
22-20086473-C-T			Likely benign (Dec 31, 2019)
22-20086477-G-T		not specified	Uncertain significance (Jan 18, 2022)
22-20086567-T-G		not specified	Uncertain significance (Jun 16, 2023)
22-20086622-C-T		not specified	Uncertain significance (May 10, 2024)
22-20086643-G-T		not specified	Uncertain significance (Nov 07, 2022)
22-20087176-C-T			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DGCR8	protein_coding	protein_coding	ENST00000351989	13	31646

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000272	125737	1	10	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.99	301	487	0.619	0.0000311	5093
Missense in Polyphen		70	192.8	0.36306		2008
Synonymous	0.303	202	208	0.973	0.0000151	1515
Loss of Function	5.16	3	36.7	0.0817	0.00000203	415

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.000131	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the microprocessor complex that acts as a RNA- and heme-binding protein 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, DGCR8 function as a molecular anchor necessary for the recognition of pri-miRNA at dsRNA-ssRNA junction and directs DROSHA to cleave 11 bp away form the junction to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs (PubMed:26027739, PubMed:26748718). The heme-bound DGCR8 dimer binds pri-miRNAs as a cooperative trimer (of dimers) and is active in triggering pri-miRNA cleavage, whereas the heme-free DGCR8 monomer binds pri-miRNAs as a dimer and is much less active. Both double-stranded and single-stranded regions of a pri-miRNA are required for its binding (PubMed:15531877, PubMed:15574589, PubMed:15589161, PubMed:16751099, PubMed:16906129, PubMed:16963499, PubMed:17159994). Specifically recognizes and binds N6-methyladenosine (m6A)-containing pri-miRNAs, a modification required for pri-miRNAs processing (PubMed:25799998). Involved in the silencing of embryonic stem cell self-renewal (By similarity). {ECO:0000250|UniProtKB:Q9EQM6, ECO:0000269|PubMed:15531877, ECO:0000269|PubMed:15574589, ECO:0000269|PubMed:15589161, ECO:0000269|PubMed:16751099, ECO:0000269|PubMed:16906129, ECO:0000269|PubMed:16963499, ECO:0000269|PubMed:17159994, ECO:0000269|PubMed:25799998, ECO:0000269|PubMed:26027739, ECO:0000269|PubMed:26748718}.
• Pathway: 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: 0.140

Intolerance Scores

• loftool: 0.0309
• rvis_EVS: -1
• rvis_percentile_EVS: 8.47

Haploinsufficiency Scores

• pHI: 0.258
• hipred: Y
• hipred_score: 0.775
• ghis: 0.606

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dgcr8
• Phenotype: muscle phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); 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); 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)

Zebrafish Information Network

• Gene name: dgcr8
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased life span

Gene ontology

• Biological process: primary miRNA processing;RNA phosphodiester bond hydrolysis, endonucleolytic
• Cellular component: nucleus;nucleoplasm;nucleolus;cytoplasm;microprocessor complex
• Molecular function: double-stranded RNA binding;ribonuclease III activity;protein binding;heme binding;identical protein binding;protein homodimerization activity;metal ion binding;primary miRNA binding