GM2A

Chr 5AR

ganglioside GM2 activator

Also known as: GM2-AP, GM2AP, SAP-3

NCBI Gene: 2760 ENSG00000196743 UniProt: P17900 OMIM: 613109

This gene encodes a glycolipid transport protein that acts as a cofactor for lysosomal beta-hexosaminidase A, extracting GM2 ganglioside molecules from membranes and presenting them for degradation. Mutations cause GM2-gangliosidosis AB variant (also called AB variant of Tay-Sachs disease), an autosomal recessive lysosomal storage disorder affecting the nervous system. The gene is not highly constrained against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a small glycolipid transport protein which acts as a substrate specific co-factor for the lysosomal enzyme beta-hexosaminidase A. Beta-hexosaminidase A, together with GM2 ganglioside activator, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Mutations in this gene result in GM2-gangliosidosis type AB or the AB variant of Tay-Sachs disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

GM2-gangliosidosis, AB variantMIM #272750

Clinical highlights

Gene-disease validity (ClinGen)

Tay-Sachs disease AB variant · ARDefinitivesufficient evidence for diagnostic panels

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

1.28

LOEUF

LOF

Mechanism· G2P

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GeneReview available — GM2A