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MANBA
mannosidase beta
The MANBA gene provides instructions for creating the beta-mannosidase enzyme, which plays a vital role in the breakdown and recycling of complex sugar molecules within cells. MANBA is responsible for producing an enzyme called beta-mannosidase.
MANBA is located on the long (q) arm of chromosome 4, at band 4q24. Arm ratio per GRCh38 - banding schematic.
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Overview
The MANBA gene encodes the beta-mannosidase enzyme, a crucial component of the cellular recycling system. This enzyme is primarily active in lysosomes, which are specialised compartments within cells responsible for digesting and breaking down waste materials.
Disruptions in the MANBA gene can lead to a condition known as beta-mannosidosis, characterised by the improper processing of certain sugar molecules. Understanding MANBA's role is important for comprehending the mechanisms behind such metabolic disorders.
What the gene does
The beta-mannosidase enzyme, produced from the MANBA gene, primarily functions within lysosomes [PMID:12701191]. These organelles are often referred to as the 'recycling centres' of the cell, where they break down complex molecules into simpler components that the cell can reuse or excrete. Specifically, beta-mannosidase is involved in the catabolism of glycoproteins, which are proteins with attached sugar chains (oligosaccharides).
The enzyme’s role is to dismantle these oligosaccharides. It specialises in the very last step of this breakdown process, specifically targeting disaccharides that contain a mannose sugar molecule [PMID:12701191]. Without functional beta-mannosidase, these sugar complexes cannot be fully degraded and can accumulate within lysosomes, leading to cellular dysfunction.
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Chromosome location
The MANBA gene is situated on chromosome 4, specifically at position 4q24. This refers to the long arm (q) of chromosome 4, in region 2, band 4. The precise genomic location helps in understanding its genetic context and how it might be inherited or affected by chromosomal changes.
Protein structure
The MANBA gene produces a protein that is 879 amino acids long. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variations within the MANBA gene can affect the production or function of the beta-mannosidase enzyme. These variations, sometimes referred to as mutations, can lead to a range of effects, from mild alterations in enzyme activity to a complete loss of function. The specific impact often depends on the type and location of the variant [PMID:10526017].
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.1398G>A | p.Trp466Ter | Pathogenic | ★★☆☆ | Beta-D-mannosidosis |
c.1434del | p.Lys479fs | Pathogenic/Likely pathogenic | ★★☆☆ | Beta-D-mannosidosis |
c.1623G>A | p.Trp541Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Beta-D-mannosidosis |
c.1648C>T | p.Arg550Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Beta-D-mannosidosis |
c.1733del | p.Asn578fs | Pathogenic | ★★☆☆ | Beta-D-mannosidosis |
c.1753C>T | p.Arg585Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Beta-D-mannosidosis |
c.2175dup | p.Ser726fs | Pathogenic/Likely pathogenic | ★★☆☆ | Beta-D-mannosidosis |
c.544C>T | p.Arg182Trp | Pathogenic/Likely pathogenic | ★★☆☆ | Beta-D-mannosidosis |
c.692G>A | p.Trp231Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Beta-D-mannosidosis |
c.916del | p.Leu306fs | Pathogenic/Likely pathogenic | ★★☆☆ | Beta-D-mannosidosis |
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
Variants in the MANBA gene are known to cause beta-mannosidosis. This inherited metabolic disorder affects the way certain sugar molecules are processed in the body, resulting in various nervous system problems.
No disease links recorded for this gene in our reference set.
UK clinical status
The MANBA gene is recognised within several UK NHS national genomic testing panels. It is listed as 'green' on the DDG2P panel, the Intellectual disability panel, the Likely inborn error of metabolism panel (R98), the Lysosomal storage disorder panel (R276), and the Undiagnosed metabolic disorders panel. A 'green' status indicates that there is strong evidence for a gene's association with a particular condition and that it is included in routine clinical testing.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main role of the MANBA gene?
The MANBA gene provides instructions for making the beta-mannosidase enzyme. This enzyme is crucial for breaking down specific sugar molecules within lysosomes, which are cellular compartments responsible for waste digestion and recycling.
What condition is associated with MANBA gene variants?
Variants in the MANBA gene are primarily associated with beta-mannosidosis. This is a rare inherited disorder that affects the body's ability to properly process certain sugar molecules, leading to their accumulation and various health issues, particularly affecting the nervous system.
Where is the MANBA gene located in the human genome?
The MANBA gene is located on chromosome 4. More specifically, its precise position is designated as 4q24, which refers to a particular band on the long arm of chromosome 4.
References
- Molho-Pessach V, Bargal R, Abramowitz Y. Angiokeratoma corporis diffusum in human beta-mannosidosis: Report of a new case and a novel mutation. Journal of the American Academy of Dermatology. 2007. PMID: 17420068
- Zhu M, Lovell KL, Patterson JS. Beta-mannosidosis mice: a model for the human lysosomal storage disease. Human molecular genetics. 2006. PMID: 16377659
- Gort L, Duque J, Fabeiro JM. Molecular analysis in two beta-mannosidosis patients: description of a new adult case. Molecular genetics and metabolism. 2006. PMID: 16904924
- Uchino Y, Fukushige T, Yotsumoto S. Morphological and biochemical studies of human beta-mannosidosis: identification of a novel beta-mannosidase gene mutation. The British journal of dermatology. 2003. PMID: 12890191
- Bedilu R, Nummy KA, Cooper A. Variable clinical presentation of lysosomal beta-mannosidosis in patients with null mutations. Molecular genetics and metabolism. 2002. PMID: 12468273
- Alkhayat AH, Kraemer SA, Leipprandt JR. Human beta-mannosidase cDNA characterization and first identification of a mutation associated with human beta-mannosidosis. Human molecular genetics. 1998. PMID: 9384606