HEXA Human
Description
Biochemical Structure and Function
HEXA Human is a 52.9 kDa polypeptide chain comprising 464 amino acids (residues 89–529) with an N-terminal His-tag in recombinant forms . As the alpha subunit of β-hexosaminidase A, it heterodimerizes with the beta subunit (encoded by HEXB) to form the functional enzyme HexA . Key structural features include:
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Catalytic loop: Amino acids Gly-280, Ser-281, Glu-282, and Pro-283 enable binding to the GM2 activator protein for substrate hydrolysis .
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Active site: Arg-424 is essential for hydrolyzing GM2 gangliosides into GM3 by cleaving terminal N-acetylgalactosamine (GalNAc) .
Table 1: Recombinant HEXA Properties1911
Genetic Mutations and Disease Association
Over 300 mutations in HEXA are linked to Tay-Sachs disease (TSD), a fatal lysosomal storage disorder. Mutations disrupt HexA folding, dimerization, or catalytic activity .
Table 2: Clinically Significant HEXA Mutations23467
Mechanisms of Pathogenicity
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Infantile TSD: Severe mutations (e.g., E482K) cause near-complete HexA deficiency (<0.1% activity) due to misfolded α-subunits aggregating in the ER .
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Late-onset TSD: Hypomorphic mutations (e.g., G269S) allow partial α/β dimerization and ~10–20% residual enzyme secretion .
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Splice variants: Mutations like c.346+2dupT produce non-functional isoforms through exon skipping, detectable via RNA sequencing .
Diagnostic and Therapeutic Insights
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Enzyme assays: TSD patients show HexA activity <5 µmol/L/h in leukocytes .
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Genetic testing: Whole-exome sequencing identifies novel mutations (e.g., c.805G>A and c.346+2dupT) .
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Therapeutic challenges: Enzyme replacement therapy and bone marrow transplantation have limited efficacy due to blood-brain barrier constraints .
Research Applications
Product Specs
Q&A
What is the HEXA study and what are its primary research objectives?
The Health Examinees (HEXA) Study is a large-scale genomic cohort study conducted in Korea to investigate epidemiologic characteristics, genomic features, and gene-environment interactions of major chronic diseases including cancer. The study was designed to address Korea's unique situation of experiencing rapid economic development in a very short period, creating a mixture of traditional and modern risk factors that interact with genetic constituents .
The primary objectives include:
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Investigating biomarkers of early health indices
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Examining chronological changes associated with chronic diseases
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Studying interactions between genetic and environmental factors
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Analyzing how these interactions influence disease development, particularly cancers
What population does the HEXA study cover and what is its sample size?
The HEXA study recruited participants aged 40-69 years from 38 health examination centers and training hospitals throughout Korea. Between 2004 and 2013, a total of 167,169 subjects were enrolled in the study . The baseline survey was implemented using a two-stage approach: phase I (2004-2008) and phase II (2009-2013). This extensive recruitment strategy ensures geographical representation across Korea, providing a comprehensive demographic sample for chronic disease research.
What biological specimens are collected in the HEXA study?
The HEXA study systematically collects and processes multiple biological specimens following a standardized protocol:
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Blood samples: At least 19 ccs of blood drawn into one serum separator tube (SST) and two ethylene-diamine-tetra-acetic acid (EDTA) tubes
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Urine samples: More than 12 ml collected in conical tubes
These samples are processed to extract and store:
All biospecimens are labeled with 2D barcodes and assigned study IDs that match participants' questionnaires, maintained under controlled temperature conditions, and collected within 24 hours by a commercial laboratory courier.
What is Human Hexosaminidase A/HEXA enzyme?
Human Hexosaminidase A (HEXA) is an enzyme detected in human tissues, including liver and brain tissue. Based on Western blot analysis, it appears as a specific band at approximately 60 kDa . In immunohistochemistry studies, HEXA has been localized to the cytoplasm and lysosomes in neuronal cell bodies, particularly in the hypothalamus .
The enzyme is derived from recombinant protein expressed in S. frugiperda insect ovarian cell line (Sf21) spanning amino acids Met1-Thr529 of the human protein, corresponding to Accession # P06865 . While the search results don't provide comprehensive information about its full biological function, the presence of specialized antibodies for its detection indicates its significance in biomedical research.
What methodologies are used for participant follow-up in the HEXA cohort study?
The HEXA study employs a comprehensive dual-approach follow-up methodology to maximize outcome data collection and minimize participant loss:
Active Follow-up:
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Began in 2012 with continuation through 2015
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Medical institutions recruit existing cohort members at 2-year intervals
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Information leaflets are mailed and phone calls are made to facilitate participation
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Follow-up visits include questionnaire completion, laboratory tests, and collection of blood and urine samples
Passive Follow-up:
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Based on data linkages with national health databases, including:
This combined approach enables researchers to comprehensively track health outcomes while maintaining participant engagement, critical for longitudinal studies examining chronic disease development.
How does the HEXA study address gene-environment interactions in chronic disease development?
The HEXA study was specifically designed to investigate the complex interplay between genetic factors and environmental exposures in disease development, utilizing several methodological approaches:
Data Integration Strategy:
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Collection of genomic DNA from blood samples
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Detailed questionnaire data on lifestyle factors, including diet, physical activity, occupation, residence history, and psychosocial factors
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Comprehensive medical history, family history, and prospective health outcome tracking
Korean Transition Context:
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The study capitalizes on Korea's rapid transition from traditional to modern lifestyles
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Documents dietary shifts such as:
The longitudinal design and biospecimen repository allow researchers to examine how these rapidly changing environmental exposures interact with genetic factors to influence chronic disease risk in the Korean population.
How is Human Hexosaminidase A/HEXA detected and measured in laboratory settings?
Human Hexosaminidase A/HEXA can be detected and quantified using several laboratory techniques:
Western Blot Analysis:
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PVDF membrane probed with Mouse Anti-Human Hexosaminidase A/HEXA Monoclonal Antibody (Clone # 714729)
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Detection using HRP-conjugated Anti-Mouse IgG Secondary Antibody
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Specific band appears at approximately 60 kDa
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Conducted under reducing conditions using Immunoblot Buffer Group 1
Immunohistochemistry (IHC):
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Detection in fixed paraffin-embedded tissue sections
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Pre-treatment with heat-induced epitope retrieval using Antigen Retrieval Reagent-Basic
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Staining with Anti-Mouse HRP-DAB Cell & Tissue Staining Kit
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Counterstaining with hematoxylin
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Specific staining localizes to cytoplasm and lysosomes in neuronal cell bodies
ELISA:
These methodological approaches provide researchers with reliable options for detecting HEXA in various biological samples and experimental settings.
What quality control measures are implemented in the HEXA study?
The HEXA study implemented rigorous quality control measures to ensure data validity:
Protocol Standardization:
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Centralized system for all procedures except sample collection (implemented in phase II)
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Computer-assisted personal interviewing system to reduce interviewer bias
Questionnaire Development:
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Based on extensive literature reviews of NIH-funded studies
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Incorporated validated instruments (KNHANES, MLTPAQ, PWI-SF)
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Underwent twice-revision using NCI's back-translation process
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Pilot tested for feasibility and efficacy before implementation
Dietary Assessment Validation:
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Semi-Quantitative Food Frequency Questionnaire (SQFFQ) with 106 food items
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Validated against 12 days of diet record data from 124 subjects
Biospecimen Management:
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Standardized collection, processing, and storage protocols
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2D barcode tracking system
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Temperature-controlled storage and transportation
These measures fulfill international standards for genomic cohort studies, ensuring research data quality and comparability with other major cohort studies worldwide.
What is the structure and content of the HEXA study questionnaire?
The HEXA questionnaire is comprehensive and meticulously structured to capture diverse factors potentially related to chronic disease development:
Table 1: Composition of the HEXA Questionnaire
| Category | Number of Items | Content Areas |
|---|---|---|
| Socio-demographic factors | 52 | Age, sex, education level, income, occupation, residence history |
| Medical history, drug usage, and family history | 501 | Disease diagnoses, treatments, family history of diseases |
| Smoking and alcohol drinking | 60 | Smoking habits, indirect smoking exposure, alcohol consumption |
| Physical activity and weight change | 245 | Sleep patterns, physical activity levels, weight history |
| Socio-psychological factors | 87 | Stress, depression (PWI-SF), social support networks |
| Reproductive factors (women) | 51 | Menstruation, pregnancy history, contraception |
| Dietary habits | 241 | Meal frequency, cooking patterns, food frequency questionnaire |
| Total | 1,303 |
The questionnaire was developed through rigorous methodology including literature review, expert consultation, back-translation processes, and pilot testing . This comprehensive assessment tool enables researchers to examine multiple risk factors and their interactions in relation to chronic disease outcomes.
How does the HEXA 3D asset platform differ from other visualization technologies in research contexts?
While primarily a commercial entity, the Hexa 3D platform has potential research applications. Unlike traditional visualization tools, Hexa combines AI-powered technology with human artistry to create and manage 3D models .
Research Applications:
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Converting scientific images to 3D models for enhanced visualization
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Creating AR/VR experiences for educational and research purposes
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Enabling 360-degree examination of complex biological structures
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Preparing 3D visual assets for research communication
The platform's API can automatically fetch images and transform them into 3D assets that can be aligned with source imagery "at a pixel and voxel level" . While originally developed for retail applications, these capabilities have potential value for medical education, anatomical visualization, and biomedical research communication.
What approaches should researchers consider when analyzing HEXA study data?
Based on the HEXA study design as a large-scale genomic cohort with follow-up components, researchers should consider these methodological approaches:
Epidemiological Methods:
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Survival analysis techniques for time-to-event outcomes
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Longitudinal data analysis for repeated measures
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Nested case-control designs for efficient biomarker analysis
Genetic Analysis:
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Gene-environment interaction models that account for Korea's rapid lifestyle transitions
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Analysis strategies that examine both traditional and modern risk factors
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Approaches that consider the unique genetic background of the Korean population
Confounding Control:
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Methods addressing the complex relationships between rapidly changing socioeconomic factors
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Approaches accounting for birth cohort effects within the 40-69 year age range
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Techniques handling the mixture of traditional and modern risk factors
The HEXA study's unique context of rapid socioeconomic transition requires analytical approaches that can disentangle these complex relationships while accounting for genetic factors.
How can researchers optimize immunohistochemical detection of HEXA in tissue samples?
For optimal immunohistochemical detection of HEXA in tissue samples, researchers should consider these methodological details:
Tissue Preparation:
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Use immersion fixed paraffin-embedded tissue sections
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Perform heat-induced epitope retrieval using Antigen Retrieval Reagent-Basic prior to antibody incubation
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Maintain consistent overnight incubation at 4°C for primary antibody binding
Antibody Selection and Concentration:
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Use Mouse Anti-Human Hexosaminidase A/HEXA Monoclonal Antibody (Clone # 714729)
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Apply at 15 μg/mL concentration for optimal signal-to-noise ratio
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Select appropriate HRP-conjugated secondary antibody systems
Visualization System:
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Implement Anti-Mouse HRP-DAB Cell & Tissue Staining Kit for chromogenic detection
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Counter-stain with hematoxylin to provide cellular context
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Examine for specific staining in cytoplasm and lysosomes of neuronal cell bodies
These methodological considerations ensure reliable and reproducible detection of HEXA in human tissue samples for research applications.
What emerging applications exist for the HEXA study dataset in precision medicine?
The HEXA study's comprehensive dataset offers significant potential for precision medicine applications:
Biomarker Development:
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The longitudinal collection of biospecimens enables identification and validation of early disease biomarkers
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Integration of genomic data with detailed environmental exposure information facilitates personalized risk prediction models
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The study's focus on chronological changes in health indices supports development of dynamic risk assessment tools
Population-Specific Insights:
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The large Korean cohort provides critical data for developing population-specific guidelines
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The captured transition from traditional to modern lifestyles offers unique insights into adaptation mechanisms
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Understanding gene-environment interactions in this population can inform targeted prevention strategies
The HEXA study's design specifically addresses Korea's unique situation of rapid transition, making it particularly valuable for developing precision medicine approaches that account for rapid environmental changes in genetically stable populations.
How might 3D visualization technologies enhance chronic disease research?
Advanced 3D visualization technologies like those developed by Hexa could transform chronic disease research through:
Enhanced Disease Modeling:
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Converting medical imaging data into interactive 3D models
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Creating AR/VR experiences for studying complex disease processes
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Enabling more intuitive visualization of multidimensional data
Research Communication:
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Developing 3D assets for educational and communication purposes
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Creating interactive visualizations of research findings for public health initiatives
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Facilitating knowledge transfer between researchers and clinicians
Methodological Applications:
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Using AI-assisted tools to transform 2D images into 3D models with "pixel and voxel level" accuracy
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Applying 3D viewer technologies to enhance interpretation of complex biological structures
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Integrating visualization technologies into research workflows
While initially developed for commercial applications, these technologies have significant potential for enhancing both the research process and the communication of findings in chronic disease studies.
Product Science Overview
Hexosaminidase A is a heterodimer consisting of one alpha and one beta subunit. The alpha subunit is encoded by the HEXA gene, while the beta subunit is encoded by the HEXB gene. The enzyme’s primary function is to hydrolyze terminal N-acetyl-D-hexosamine residues in GM2 gangliosides and other glycosphingolipids .
Recombinant human Hexosaminidase A is produced using baculovirus expression systems in insect cells, such as Spodoptera frugiperda (Sf21). The recombinant protein typically includes a C-terminal His-tag for purification purposes . The recombinant form is used in various research applications, including studies on lysosomal storage disorders and enzyme replacement therapies.
Mutations in the HEXA gene can lead to a deficiency in Hexosaminidase A activity, resulting in the accumulation of GM2 gangliosides in neurons. This accumulation causes a group of lysosomal storage disorders known as GM2 gangliosidoses, the most well-known of which is Tay-Sachs disease . Tay-Sachs disease is characterized by progressive neurodegeneration, leading to severe physical and mental disabilities.
