GLB1 across dismech

GLB1 (galactosidase beta 1) is named by 5 disorder entries: the three GM1 gangliosidosis types and two mucopolysaccharidosis entries.

Normal function

ai-gene-review gives GLB1's core molecular function as beta-galactosidase activity, acting in ganglioside catabolic process; and keratan sulfate proteoglycan catabolic process in the lysosomal lumen; and lysosome. The two processes correspond to the two allelic disease groups: GM1 ganglioside storage and keratan sulfate storage.

Causative records

Every entry types GLB1 as causative: GM1 Gangliosidosis Type 1; GM1 Gangliosidosis Type 2; GM1 Gangliosidosis Type 3; Morquio syndrome; and Mucopolysaccharidosis, and all record the variants as germline (GM1 Gangliosidosis Type 1; GM1 Gangliosidosis Type 2; GM1 Gangliosidosis Type 3; Morquio syndrome; and Mucopolysaccharidosis).

The GM1 gangliosidosis types differ by how much enzyme activity remains, and their molecular nodes say so. Type 1 puts GLB1 on GLB1 Loss of Function and Beta-Galactosidase Deficiency; type 2 on Partial Beta-Galactosidase Deficiency and GM1 Ganglioside Accumulation; and type 3 on Partial Beta-Galactosidase Deficiency with Basal Ganglia GM1 Accumulation. The Morquio entry puts it on Type B GLB1 deficiency with keratan sulfate-biased catalytic loss. Nodes naming GLB1 conform to the modules lysosomal_substrate_accumulation; and mps_gag_storage.

ClinGen rates GLB1 definitive for mucopolysaccharidosis type 4B, matched to the Morquio syndrome entry.

Where the layers disagree

ClinGen classifies GLB1 for 2 diseases. The one with no matching dismech entry is GM1 gangliosidosis: ClinGen's definitive assertion is made for GM1 gangliosidosis as a whole, while dismech curates the three types separately, so the assertion is not recorded on any of them.

The KB's GLB1 nodes and the ai-gene-review core function share ganglioside catabolic process as a GO process. The KB's GLB1 nodes are annotated with ganglioside catabolic process; glycosaminoglycan catabolic process; and lysosomal transport, so the keratan sulfate side does not line up by exact identifier: the KB uses the broader glycosaminoglycan process where ai-gene-review names keratan sulfate proteoglycan catabolic process.