HEXA
Chr 15ARhexosaminidase subunit alpha
Also known as: TSD
This gene encodes a member of the glycosyl hydrolase 20 family of proteins. The encoded preproprotein is proteolytically processed to generate the alpha subunit of the lysosomal enzyme beta-hexosaminidase. This enzyme, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Mutations in this gene lead to an accumulation of GM2 ganglioside in neurons, the underlying cause of neurodegenerative disorders termed the GM2 gangliosidoses, including Tay-Sachs disease (GM2-gangliosidosis type I). Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
This gene — mechanism propensity
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
HEXA · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Translational Potential of ex Vivo Gene Therapy in GM2 Gangliosidosis
NOT YET RECRUITINGThe Myelin Disorders Biorepository Project
RECRUITINGLong-Term Follow-Up of Subjects Treated With AXO-AAV-GM2 for Tay-Sachs or Sandhoff Disease
ACTIVE NOT RECRUITINGA Natural History Study of the Gangliosidoses
RECRUITINGFirst-in-Human Study of TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools