On this page
HEXB
hexosaminidase subunit beta
The HEXB gene provides instructions for a key component of enzymes crucial for breaking down specific fatty compounds and sugars within nerve cells. HEXB encodes the beta subunit of beta-hexosaminidase A and B enzymes, which are vital for lysosomal function in the central nervous system.
HEXB is located on the long (q) arm of chromosome 5, at band 5q13.3. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 5 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The HEXB gene is responsible for producing the beta subunit of two related enzymes: beta-hexosaminidase A and beta-hexosaminidase B. These enzymes are critical for the proper functioning of nerve cells, particularly in the brain and spinal cord, where they help break down complex molecules.
Inherited in an autosomal recessive pattern, variants in the HEXB gene are associated with conditions like Sandhoff disease. Understanding the role of HEXB is important for carrier screening and diagnosing certain metabolic disorders.
What the gene does
The protein produced from the HEXB gene serves as the beta subunit for both beta-hexosaminidase A and beta-hexosaminidase B enzymes. Beta-hexosaminidase A is formed from one alpha subunit (encoded by the HEXA gene) and one beta subunit, while beta-hexosaminidase B comprises two beta subunits.
These enzymes are located within lysosomes, which are cellular compartments responsible for degrading and recycling waste products. Specifically, they break down fatty compounds called sphingolipids, complex sugars known as oligosaccharides, and molecules linked to sugars. Beta-hexosaminidase A is particularly important for catabolising a fatty substance called GM2 ganglioside, preventing its accumulation in cells, which is crucial for neuronal health.
Video: Genetics 101
Chromosome location
The HEXB gene is situated on chromosome 5, specifically at position 5q13.3. The gene provides instructions for a protein that is 556 amino acids long.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the HEXB gene can lead to reduced or absent activity of the beta-hexosaminidase A and B enzymes. These changes can impair the enzymes' ability to break down their target molecules, resulting in the harmful accumulation of these substances within cells.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1408_1409insCA | p.Asp470fs | Pathogenic/Likely pathogenic | ★★☆☆ | Sandhoff disease |
c.1431_1432del | p.Lys478fs | Pathogenic | ★★☆☆ | Sandhoff disease |
c.1434dup | p.Gln479fs | Pathogenic/Likely pathogenic | ★★☆☆ | Sandhoff disease |
c.1435_1436del | p.Gln479fs | Pathogenic/Likely pathogenic | ★★☆☆ | Sandhoff disease |
c.1640dup | p.Tyr547Ter | Pathogenic | ★★☆☆ | Sandhoff disease |
c.341_342del | p.Glu114fs | Pathogenic/Likely pathogenic | ★★☆☆ | Sandhoff disease |
c.534_537del | p.Leu178fs | Pathogenic | ★★☆☆ | Sandhoff disease |
c.738T>A | p.Tyr246Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Sandhoff disease |
c.838_863dup | p.Glu288fs | Pathogenic/Likely pathogenic | ★★☆☆ | Sandhoff disease |
c.899_900dup | p.Gly301fs | Pathogenic/Likely pathogenic | ★★☆☆ | Sandhoff disease |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the HEXB gene are primarily associated with Sandhoff disease. This is an autosomal recessive lysosomal storage disorder characterised by the toxic build-up of specific fatty substances and sugars within cells, particularly in the nervous system. The severity and onset of symptoms can vary, typically affecting neurological function.
- Sandhoff disease Dedicated page coming soon
Inheritance pattern
Conditions caused by pathogenic HEXB variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The HEXB gene is part of several NHS Genomic Medicine Service national panels, indicating its clinical significance in the UK. It is included in panels for "Sandhoff disease", "Lysosomal storage disorder", "Likely inborn error of metabolism", and "Hereditary neuropathy or pain disorder", among others. This widespread inclusion reflects its established role in various neurological and metabolic conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the function of the HEXB gene?
The HEXB gene provides the blueprint for the beta subunit of beta-hexosaminidase A and B enzymes. These enzymes are crucial for breaking down fatty compounds and complex sugars within the lysosomes of nerve cells.
Which condition is primarily associated with HEXB gene variants?
Variants in the HEXB gene are primarily associated with Sandhoff disease. This is a severe inherited disorder characterised by the accumulation of specific fatty substances in the brain and spinal cord due to impaired enzyme function.
How is Sandhoff disease inherited?
Sandhoff disease is inherited in an autosomal recessive manner. This means that an individual must inherit two altered copies of the HEXB gene (one from each parent) to develop the condition. People with only one altered copy are carriers and typically do not show symptoms.
References
- Mark BL, Mahuran DJ, Cherney MM. Crystal structure of human beta-hexosaminidase B: understanding the molecular basis of Sandhoff and Tay-Sachs disease. Journal of molecular biology. 2003. PMID: 12662933
- Maier T, Strater N, Schuette CG. The X-ray crystal structure of human beta-hexosaminidase B provides new insights into Sandhoff disease. Journal of molecular biology. 2003. PMID: 12706724
- Myerowitz R, Lawson D, Mizukami H. Molecular pathophysiology in Tay-Sachs and Sandhoff diseases as revealed by gene expression profiling. Human molecular genetics. 2002. PMID: 12019216