AGRN

Chr 1AR

agrin

Also known as: AGRIN, CMS8, CMSPPD

NCBI Gene: 375790 ENSG00000188157 UniProt: O00468 OMIM: 103320

The protein encoded by this gene is critical for neuromuscular junction development and contains multiple functional domains including laminin G, Kazal type serine protease inhibitor, and epidermal growth factor domains. Mutations cause congenital myasthenic syndrome type 8 with pre- and postsynaptic defects affecting limb-girdle muscles through an autosomal recessive inheritance pattern. The pathogenic mechanism involves gain-of-function effects of the mutant protein.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes one of several proteins that are critical in the development of the neuromuscular junction (NMJ), as identified in mouse knock-out studies. The encoded protein contains several laminin G, Kazal type serine protease inhibitor, and epidermal growth factor domains. Additional post-translational modifications occur to add glycosaminoglycans and disulfide bonds. In one family with congenital myasthenic syndrome affecting limb-girdle muscles, a mutation in this gene was found. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2015]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Myasthenic syndrome, congenital, 8, with pre- and postsynaptic defectsMIM #615120

Clinical highlights

Gene-disease validity (ClinGen)

congenital myasthenic syndrome 8 · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.43

LOEUF

Multiple*

Mechanism· predicted