DGCR6

Chr 22

DiGeorge syndrome critical region gene 6

NCBI Gene: 8214ENSG00000183628UniProt: Q14129

DiGeorge syndrome, and more widely, the CATCH 22 syndrome, are associated with microdeletions in chromosomal region 22q11.2. The product of this gene shares homology with the Drosophila melanogaster gonadal protein, which participates in gonadal and germ cell development, and with the gamma-1 subunit of human laminin. This gene is a candidate for involvement in DiGeorge syndrome pathology and in schizophrenia. [provided by RefSeq, Nov 2008]

393
ClinVar variants
297
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DGCR6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
297 Pathogenic / Likely Pathogenic· 71 VUS of 393 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.83LOEUF
pLI 0.000
Z-score -0.88
OE 1.28 (0.85–1.83)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.14Z-score
OE missense 1.03 (0.90–1.20)
130 obs / 125.7 exp
Tolerant

Tolerant to missense variation

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.1.28 (0.85–1.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.90–1.20)
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.1.13
0≤1.21.6
LoF obs/exp: 15 / 11.8Missense obs/exp: 130 / 125.7Syn Z: -0.74

ClinVar Variant Classifications

393 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic289
Likely Pathogenic8
VUS71
Likely Benign12
Benign5
289
Pathogenic
8
Likely Pathogenic
71
VUS
12
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
289
0
289
Likely Pathogenic
0
0
8
0
8
VUS
0
48
23
0
71
Likely Benign
0
2
7
3
12
Benign
0
0
4
1
5
Total0503314385

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

View in ClinVar →

Protein Context — Lollipop Plot

DGCR6 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A chicken model for DGCR6 as a modifier gene in the DiGeorge critical region.
Hierck BP et al.·Pediatr Res
2004Functional
Targetable molecular alterations in congenital glioblastoma.
Gilani A et al.·J Neurooncol
2020
The impact of 22q11.2 copy-number variants on human traits in the general population.
Zamariolli M et al.·Am J Hum Genet
2023
Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation.
Guilmatre A et al.·Arch Gen Psychiatry
2009Review
The 22q11 PRODH/DGCR6 deletion is frequent in hyperprolinemic subjects but is not a strong risk factor for ASD.
Richard AC et al.·Am J Med Genet B Neuropsychiatr Genet
2016
Systematic analysis of copy number variants of a large cohort of orofacial cleft patients identifies candidate genes for orofacial clefts.
Conte F et al.·Hum Genet
2016Cohort
Copy number variation analysis in bicuspid aortic valve-related aortopathy identifies TBX20 as a contributing gene.
Luyckx I et al.·Eur J Hum Genet
2019Clinical trial
Atypical microdeletion 22q11.2 in a patient with tetralogy of Fallot.
Carli D et al.·J Genet
2021Case report
Refining the 22q11.2 deletion breakpoints in DiGeorge syndrome by aCGH.
Bittel DC et al.·Cytogenet Genome Res
2009
Allelic expression patterns of imprinted and non-imprinted genes in cancer cell lines from multiple histologies.
Krushkal J et al.·Clin Epigenetics
2025
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