DGCR6L

Chr 22

DiGeorge syndrome critical region gene 6 like

Also known as: DGCR6

NCBI Gene: 85359ENSG00000128185UniProt: Q9BY27OMIM: 609459

The protein encoded by this gene may function in neural crest cell migration into the third and fourth pharyngeal pouches and shares homology with proteins involved in cell attachment and migration. This gene is located within the chromosome 22q11.2 region associated with DiGeorge syndrome, though specific disease associations with isolated DGCR6L mutations have not been established. The gene is highly tolerant to loss-of-function variants based on population data.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.27
Clinical Summary— DGCR6L
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
370 unique Pathogenic / Likely Pathogenic· 46 VUS of 429 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.27LOEUF
pLI 0.000
Z-score 0.93
OE 0.70 (0.41–1.27)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.54Z-score
OE missense 0.87 (0.74–1.01)
114 obs / 131.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.70 (0.41–1.27)
0≤0.351.4
Missense OE0.87 (0.74–1.01)
0≤0.61.4
Synonymous OE0.86
0≤1.21.6
LoF obs/exp: 8 / 11.4Missense obs/exp: 114 / 131.2Syn Z: 0.80
DN
0.7325th %ile
GOF
0.83top 10%
LOF
0.2485th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

429 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic363
Likely Pathogenic7
VUS46
Likely Benign3
Benign2
363
Pathogenic
7
Likely Pathogenic
46
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————363
Likely Pathogenic
————7
VUS
————46
Likely Benign
————3
Benign
————2
Total—421

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DGCR6L · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients