DGCR8

Chr 22

DGCR8 microprocessor complex subunit

Also known as: C22orf12, DGCRK6, Gy1, pasha

NCBI Gene: 54487ENSG00000128191UniProt: Q8WYQ5

This gene encodes a subunit of the microprocessor complex which mediates the biogenesis of microRNAs from the primary microRNA transcript. The encoded protein is a double-stranded RNA binding protein that functions as the non-catalytic subunit of the microprocessor complex. This protein is required for binding the double-stranded RNA substrate and facilitates cleavage of the RNA by the ribonuclease III protein, Drosha. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2010]

495
ClinVar variants
375
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DGCR8
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
375 Pathogenic / Likely Pathogenic· 87 VUS of 495 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.21LOEUF
pLI 1.000
Z-score 5.16
OE 0.08 (0.04–0.21)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.99Z-score
OE missense 0.62 (0.56–0.68)
301 obs / 486.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.04–0.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.62 (0.56–0.68)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 3 / 36.7Missense obs/exp: 301 / 486.6Syn Z: 0.30

ClinVar Variant Classifications

495 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic366
Likely Pathogenic9
VUS87
Likely Benign26
Benign6
Conflicting1
366
Pathogenic
9
Likely Pathogenic
87
VUS
26
Likely Benign
6
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
366
0
366
Likely Pathogenic
0
0
9
0
9
VUS
1
72
14
0
87
Likely Benign
0
5
2
19
26
Benign
0
0
2
4
6
Conflicting
—1
Total17739323495

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

View in ClinVar →

Protein Context — Lollipop Plot

DGCR8 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
📖
GeneReview available — DGCR8
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Review of the Pathophysiology and Clinical Manifestations of 22q11.2 Deletion and Duplication Syndromes.
Purow J et al.·Clin Rev Allergy Immunol
2025Review
A functional connection between the Microprocessor and a variant NEXT complex.
Imamura K et al.·Mol Cell
2024Functional
Whole-Exome Sequencing Among Chinese Patients With Hereditary Diffuse Gastric Cancer.
Liu ZX et al.·JAMA Netw Open
2022Cohort
DICER1 and DGCR8 in thyroid tumorigenesis: miRNA biogenesis and histopathologic diversity.
Rodrigues L et al.·Eur Thyroid J
2025Review
MicroRNA-200 Loaded Lipid Nanoparticles Promote Intestinal Epithelium Regeneration in Canonical MicroRNA-Deficient Mice.
Wei X et al.·ACS Nano
2023
DGCR8 haploinsufficiency leads to primate-specific RNA dysregulation and pluripotency defects.
Colomer-Boronat A et al.·Nucleic Acids Res
2025
N4-acetylcytidine modifies primary microRNAs for processing in cancer cells.
Zhang H et al.·Cell Mol Life Sci
2024
Prevalence, Molecular Landscape, and Clinical Impact of DICER1 and DGCR8 Mutated Follicular-Patterned Thyroid Nodules.
Condello V et al.·J Clin Endocrinol Metab
2024
miRNA biogenesis and inherited disorders: clinico-molecular insights.
Pelletier D et al.·Trends Genet
2023Review
Parameters of clustered suboptimal miRNA biogenesis.
Shang R et al.·Proc Natl Acad Sci U S A
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools