HEXA
Chr 15ARhexosaminidase subunit alpha
Also known as: TSD
This gene encodes the alpha subunit of beta-hexosaminidase A, a lysosomal enzyme that degrades GM2 ganglioside and other molecules containing terminal N-acetyl hexosamines. Biallelic mutations cause autosomal recessive GM2 gangliosidosis, including Tay-Sachs disease, due to GM2 ganglioside accumulation in neurons leading to neurodegeneration. The pathogenic mechanism involves loss of enzymatic function resulting in toxic substrate accumulation.
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
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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
First-in-Human Study of TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis
ACTIVE NOT RECRUITINGLong-Term Follow-Up of Subjects Treated With AXO-AAV-GM2 for Tay-Sachs or Sandhoff Disease
ACTIVE NOT RECRUITINGThe Myelin Disorders Biorepository Project
RECRUITINGA Natural History Study of the Gangliosidoses
RECRUITINGTranslational Potential of ex Vivo Gene Therapy in GM2 Gangliosidosis
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools