HEXA Gene (Hexosaminidase A)
Beta-hexosaminidase subunit alpha, lysosomal enzyme, associated with Tay-Sachs disease
Gene Information Card
| Symbol | HEXA |
|---|---|
| Full Name | Hexosaminidase A (alpha polypeptide) |
| Gene Type | Protein coding |
| Chromosomal Location | 15q23 |
| NCBI Gene ID | 3073 ncbi.nlm.nih.gov/gene/3073 |
| Ensembl ID | ENSG00000128272 |
| UniProt ID | P06865 |
| OMIM ID | 606869 |
| HGNC ID | 4878 |
| Aliases | Tay-Sachs disease, GM2 gangliosidosis, hexosaminidase A |
Description
The HEXA gene encodes the alpha subunit of beta-hexosaminidase A, a lysosomal enzyme that catalyzes the hydrolysis of GM2 gangliosides and other glycoconjugates. Mutations in HEXA cause Tay-Sachs disease (GM2 gangliosidosis type 1), a severe neurodegenerative disorder. The gene is located on chromosome 15q23 and is expressed in various tissues, with highest levels in the brain.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Tay-Sachs disease | Loss-of-function mutations in HEXA lead to deficiency of hexosaminidase A, resulting in accumulation of GM2 ganglioside in neurons, causing progressive neurodegeneration. | ClinVar, OMIM |
| GM2 gangliosidosis type 1 | Same mechanism as Tay-Sachs; autosomal recessive disorder due to HEXA mutations. | ClinVar, OMIM |
| Sandhoff disease | Although primarily caused by HEXB mutations, HEXA variants can modify phenotype. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Liver | 8.3 | Medium |
| Kidney | 6.1 | Medium |
| Heart | 4.7 | Low |
| Lung | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression |
| HepG2 (hepatocellular carcinoma) | 9.8 | Medium expression |
| HEK293 (embryonic kidney) | 7.4 | Medium expression |
| A549 (lung carcinoma) | 4.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1274_1277dupTATC (p.Tyr427Ilefs*5) | Frameshift insertion | Common in Ashkenazi Jewish population | Loss of function |
| c.805G>A (p.Gly269Ser) | Missense | Common in non-Jewish populations | Loss of function |
| c.1421+1G>C | Splice site | Rare | Loss of function |
| c.739C>T (p.Arg247Trp) | Missense | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most HEXA mutations cause complete or partial loss of hexosaminidase A enzymatic activity, leading to GM2 ganglioside accumulation.
Gain of Function (GOF)
No gain-of-function mutations reported for HEXA.
Dominant Negative (DN)
No dominant-negative mutations reported; HEXA-associated disorders are autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • beta-N-acetylhexosaminidase activity (GO:0004563) | • lysosome (GO:0005764) |
| • ganglioside catabolic process (GO:0006689) | • carbohydrate metabolic process (GO:0005975) |
| • protein binding (GO:0005515) |
Pathways
• Glycosphingolipid metabolism (KEGG: hsa00600)
• Lysosome (KEGG: hsa04142)
• GM2 ganglioside degradation (Reactome: R-HSA-1660662)
Protein Summary
The HEXA gene encodes the alpha subunit of beta-hexosaminidase A (UniProt P06865), a lysosomal enzyme that forms a heterodimer with the beta subunit (HEXB). This enzyme is essential for the degradation of GM2 gangliosides. Deficiency due to mutations leads to Tay-Sachs disease. The protein is synthesized as a preproprotein and processed into mature forms. It is expressed in many tissues, with highest levels in the brain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HEXA Knockout HEK293 Cell Line | EDJ-KQ4857 | Human | 3073 | Details Get a Quote |
| HEXA Knockout A-549 Cell Line | EDJ-KQ26424 | Human | 3073 | Details Get a Quote |
| HEXA Knockout HCT 116 Cell Line | EDJ-KQ27635 | Human | 3073 | Details Get a Quote |
| HEXA Knockout HeLa Cell Line | EDJ-KQ27636 | Human | 3073 | Details Get a Quote |
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