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…

Primary Disease Associations & Inheritance

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9MIM #616538

Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9MIM #613818

Clinical highlights

Gene-disease validity (ClinGen)

neuromuscular disease caused by qualitative or quantitative defects of alpha-dystroglycan · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.30

LOEUF· LoF intol.

LOF

Mechanism· G2P