ALG2

Chr 9AR

ALG2 alpha-1,3/1,6-mannosyltransferase

Also known as: CDG1I, CDGIi, CMS14, CMSTA3, NET38, hALPG2

NCBI Gene: 85365 ENSG00000119523 UniProt: O75340 OMIM: 607905

The protein functions as an alpha 1,3 mannosyltransferase in the endoplasmic reticulum, catalyzing the addition of mannose residues to dolichol-linked oligosaccharide precursors during N-linked glycosylation. Biallelic mutations cause congenital disorder of glycosylation type Ii and congenital myasthenic syndrome type 14 with tubular aggregates, both inherited in an autosomal recessive pattern. The pathogenic mechanism involves dominant-negative effects that disrupt normal protein glycosylation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the glycosyltransferase 1 family. The encoded protein acts as an alpha 1,3 mannosyltransferase, mannosylating Man(2)GlcNAc(2)-dolichol diphosphate and Man(1)GlcNAc(2)-dolichol diphosphate to form Man(3)GlcNAc(2)-dolichol diphosphate. Defects in this gene have been associated with congenital disorder of glycosylation type Ih (CDG-Ii). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IiMIM #607906

Myasthenic syndrome, congenital, 14, with tubular aggregatesMIM #616228

Clinical highlights

Gene-disease validity (ClinGen)

ALG2-congenital disorder of glycosylation · ARStrongappropriate for clinical testing

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.18

LOEUF

LOF

Mechanism· G2P

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GeneReview available — ALG2