DAG1

Chr 3AR

dystroglycan 1

Also known as: 156DAG, A3a, AGRNR, DAG, LGMDR16, MDDGA9, MDDGC7, MDDGC9

Dystroglycan is a central component of the dystrophin-glycoprotein complex that links the extracellular matrix to the cytoskeleton in skeletal muscle and is involved in laminin binding, sarcolemmal stability, and synapse formation. Mutations cause autosomal recessive muscular dystrophy-dystroglycanopathy, which ranges from severe congenital forms with brain and eye anomalies to milder limb-girdle presentations. The gene is highly constrained against loss-of-function variants, reflecting its critical role in muscle and nervous system development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.302 OMIM phenotypes
Clinical SummaryDAG1
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Gene-Disease Validity (ClinGen)
qualitative or quantitative defects of alpha-dystroglycan · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.981
Z-score 3.84
OE 0.10 (0.040.30)
Highly constrained

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

Missense Constraint
0.63Z-score
OE missense 0.92 (0.860.99)
494 obs / 534.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.10 (0.040.30)
00.351.4
Missense OE0.92 (0.860.99)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 2 / 20.9Missense obs/exp: 494 / 534.7Syn Z: -1.34
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveDAG1-related congenital muscular dystrophy-dystroglycanopathy with brain and eye anomaliesLOFAR
definitiveDAG1-related muscular dystrophy-dystroglycanopathy limb-girdleOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.3296th %ile
GOF
0.3690th %ile
LOF
0.67top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

DAG1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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