HEXD Gene (Hexosaminidase D)
Beta-hexosaminidase subunit delta; GM2 ganglioside degradation
Gene Information Card
| Symbol | HEXD |
|---|---|
| Full Name | Hexosaminidase D (beta-hexosaminidase subunit delta) |
| Gene Type | Protein coding |
| Chromosomal Location | 17q25.3 |
| NCBI Gene ID | 284207 ncbi.nlm.nih.gov/gene/284207 |
| Ensembl ID | ENSG00000109099 |
| UniProt ID | Q8IZJ3 |
| OMIM ID | 606540 |
| HGNC ID | 26516 |
| Aliases | HEXA-D, beta-hexosaminidase subunit delta, Gm2a ganglioside degradation enzyme |
Description
The HEXD gene encodes the delta subunit of beta-hexosaminidase, a lysosomal enzyme that catalyzes the degradation of GM2 gangliosides and other glycoconjugates. The delta subunit forms a heterodimer with the alpha (HEXA) or beta (HEXB) subunits, modulating substrate specificity. Mutations in HEXD are associated with GM2 gangliosidosis variants, including Sandhoff disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Sandhoff disease (GM2 gangliosidosis type II) | Deficiency of beta-hexosaminidase activity due to HEXD mutations leads to accumulation of GM2 ganglioside in lysosomes, causing neurodegeneration. | ClinVar, OMIM |
| GM2 gangliosidosis, AB variant | Mutations in HEXD impair the delta subunit's ability to form functional hexosaminidase complexes, resulting in impaired GM2 degradation. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 6.7 | Low |
| Testis | 15.2 | Medium |
| Lung | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.0 | High expression |
| SH-SY5Y | 22.5 | Neuronal model, high expression |
| HepG2 | 9.8 | Moderate expression |
| K562 | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1072C>T (p.Arg358Ter) | Nonsense | <0.01% | Loss of function; truncated protein |
| c.1495G>A (p.Gly499Arg) | Missense | <0.01% | Reduced enzyme activity |
| c.1786_1787del (p.Leu596fs) | Frameshift | <0.01% | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in HEXD cause complete loss of beta-hexosaminidase delta subunit activity, leading to GM2 accumulation.
Gain of Function (GOF)
No gain-of-function mutations reported for HEXD.
Dominant Negative (DN)
No dominant-negative mutations reported for HEXD.
View complete mutation data：
Gene Ontology (GO)
| • beta-hexosaminidase activity (GO:0004563) | • lysosome (GO:0005764) |
| • ganglioside catabolic process (GO:0006689) | • hydrolase activity (GO:0016787) |
Pathways
• Glycosphingolipid metabolism (KEGG: hsa00600)
• Lysosome (KEGG: hsa04142)
• GM2 ganglioside degradation (Reactome: R-HSA-1660662)
Protein Summary
The HEXD protein (UniProt Q8IZJ3) is a 556-amino acid lysosomal hydrolase that functions as the delta subunit of beta-hexosaminidase. It forms heterodimers with the alpha (HEXA) or beta (HEXB) subunits, enabling the degradation of GM2 gangliosides and other glycoconjugates. The protein is synthesized as a preproprotein and processed to its mature form in the lysosome. Defects in HEXD lead to lysosomal storage disorders, particularly Sandhoff disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HEXD Knockout HEK293 Cell Line | EDJ-KQ13744 | Human | 284004 | Details Get a Quote |
| HEXD Knockout HCT 116 Cell Line | EDJ-KQ42252 | Human | 284004 | Details Get a Quote |
| HEXD Knockout A-549 Cell Line | EDJ-KQ43511 | Human | 284004 | Details Get a Quote |
| HEXD Knockout HeLa Cell Line | EDJ-KQ43513 | Human | 284004 | Details Get a Quote |
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