DGCR8

Chr 22

DGCR8 microprocessor complex subunit

Also known as: C22orf12, DGCRK6, Gy1, pasha

The protein functions as a component of the microprocessor complex that recognizes and binds primary microRNA transcripts, directing their cleavage by DROSHA to initiate microRNA biogenesis. Mutations cause DiGeorge syndrome and related developmental disorders with cardiac defects, immunodeficiency, and developmental delay, following an autosomal dominant inheritance pattern. The gene is highly constrained against loss-of-function variants (pLI 0.9997, LOEUF 0.211), reflecting its essential role in cellular regulation.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.21
Clinical SummaryDGCR8
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.21LOEUF
pLI 1.000
Z-score 5.16
OE 0.08 (0.040.21)
Highly constrained

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

Missense Constraint
2.99Z-score
OE missense 0.62 (0.560.68)
301 obs / 486.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.08 (0.040.21)
00.351.4
Missense OE0.62 (0.560.68)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 3 / 36.7Missense obs/exp: 301 / 486.6Syn Z: 0.30
DN
0.2599th %ile
GOF
0.3590th %ile
LOF
0.81top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.21

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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