DAG1

Chr 3AR

dystroglycan 1

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

NCBI Gene: 1605 ENSG00000173402 UniProt: Q14118 OMIM: 128239

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes dystroglycan, a central component of dystrophin-glycoprotein complex that links the extracellular matrix and the cytoskeleton in the skeletal muscle. The encoded preproprotein undergoes O- and N-glycosylation, and proteolytic processing to generate alpha and beta subunits. Certain mutations in this gene are known to cause distinct forms of muscular dystrophy. Alternative splicing results in multiple transcript variants, all encoding the same protein. [provided by RefSeq, Nov 2015]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.302 OMIM phenotypes

Clinical Summary— DAG1

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Gene-Disease Validity (ClinGen)

neuromuscular disease caused by qualitative or quantitative defects of alpha-dystroglycan · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.981

Z-score 3.84

OE 0.10 (0.04–0.30)

Highly constrained

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

Missense Constraint?

0.63Z-score

OE missense 0.92 (0.86–0.99)

494 obs / 534.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.04–0.30)

0≤0.351.4

Missense OE?0.92 (0.86–0.99)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

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

This gene — mechanism propensity

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

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.