DGCR8

Chr 22

DGCR8 microprocessor complex subunit

Also known as: C22orf12, DGCRK6, Gy1, pasha

NCBI Gene: 54487 ENSG00000128191 UniProt: Q8WYQ5 OMIM: 609030

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.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.21

Clinical Summary— DGCR8

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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.

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ClinVar Variants

42 VUS of 83 total submissions

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GeneReview available — DGCR8

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.08 (0.04–0.21)

0≤0.351.4

Missense OE?0.62 (0.56–0.68)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 3 / 36.7Missense obs/exp: 301 / 486.6Syn Z: 0.30

This gene — mechanism propensity

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

83 submitted variants in ClinVar

ClinVar

Classification Summary

VUS42

Likely Benign20

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	42	0	0	42
Likely Benign	2	2	16	20
Benign	0	0	4	4
Total	44	2	20	66

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

View in ClinVar →

330 pathogenic / likely-pathogenic (of 345) ClinVar copy-number / structural variants overlap DGCR8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →