LARGE1

Chr 22

LARGE xylosyl- and glucuronyltransferase 1

Also known as: LARGE, MDC1D, MDDGA6, MDDGB6

NCBI Gene: 9215 ENSG00000133424 UniProt: O95461

LARGE1 encodes a glycosyltransferase that adds xylose and glucuronic acid to alpha-dystroglycan, enabling alpha-dystroglycan to bind laminin 211 and neurexin. Autosomal recessive mutations cause muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A6) or intellectual disability (type B6) due to abnormal glycosylation of alpha-dystroglycan. Loss-of-function mutations disrupt the critical glycosylation pathway required for proper dystroglycan function in muscle and brain development.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the N-acetylglucosaminyltransferase gene family. It encodes a glycosyltransferase which participates in glycosylation of alpha-dystroglycan, and may carry out the synthesis of glycoprotein and glycosphingolipid sugar chains. It may also be involved in the addition of a repeated disaccharide unit. The protein encoded by this gene is the glycotransferase that adds the final xylose and glucuronic acid to alpha-dystroglycan and thereby allows alpha-dystroglycan to bind ligands including laminin 211 and neurexin. Mutations in this gene cause several forms of congenital muscular dystrophy characterized by cognitive disability and abnormal glycosylation of alpha-dystroglycan. Alternative splicing of this gene results in multiple transcript variants that encode the same protein. [provided by RefSeq, May 2018]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMuscular dystrophy-dystroglycanopathy congenital with impaired intellectual development B6

UniProtMuscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A6

Clinical highlights

Gene-disease validity (ClinGen)

muscular dystrophy-dystroglycanopathy · 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

—

P/LP missense

0.29

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429