Recombinant Human WSC domain-containing protein 2 (WSCD2)

What is WSCD2 and where is it located in the human genome?

WSCD2 (WSC domain containing 2) is a protein-coding gene located on chromosome 12q23.3 in humans. It contains 13 exons spanning a genomic region from position 108129288 to 108250537 on chromosome 12 (NC_000012.12). The gene encodes a protein that is predicted to enable sulfotransferase activity and is believed to be localized primarily to the Golgi membrane of cells .

What protein domains characterize WSCD2?

WSCD2 is characterized by the presence of WSC domains, which are protein domains originally identified in cell wall integrity and stress response component proteins. While detailed structural information about human WSCD2 is limited in the provided search results, the protein is defined by its WSC domain content. These domains typically contain approximately 90 amino acids and may function in carbohydrate binding or protein-protein interactions related to cell wall integrity and stress responses in eukaryotic cells .

What are the primary biological functions of WSCD2?

Based on current research, WSCD2 is predicted to enable sulfotransferase activity, suggesting a role in cellular sulfation processes. It is likely involved in post-translational modifications of proteins or other biomolecules within the Golgi apparatus. Its precise biological functions remain under investigation, but its association with personality traits and psychiatric conditions suggests potential roles in neurobiological processes .

What genetic variants in WSCD2 have been identified in genome-wide association studies?

Genome-wide association studies have identified significant associations between WSCD2 variants and personality traits. Most notably, rs1426371, an intronic variant in WSCD2, has been associated with conscientiousness. This single nucleotide polymorphism (SNP) demonstrated significant association in a large meta-analysis with a combined sample size of 169,507 individuals and reached genome-wide significance (P = 9.54×10^-15) .

The genetic architecture of this association is summarized in the following table:

How should researchers interpret the significance of WSCD2 variants in relation to phenotypes?

When interpreting WSCD2 genetic variants and their relationship to phenotypes like personality traits, researchers should consider several methodological aspects:

• Effect size interpretation: The identified WSCD2 variant (rs1426371) explained approximately 0.0354% of variance in conscientiousness (R² = 0.0354). While this appears small, it's typical of complex trait genetics where individual variants usually confer small effects .

• Replication across populations: The strength of the WSCD2 finding is supported by replication across multiple independent cohorts, including 23andMe samples, deCODE samples, and UK Biobank, suggesting robustness of the association .

• Biological context: Researchers should examine the variant in context of gene expression data. The WSCD2 variant has been identified as an expression quantitative trait locus (eQTL) for brain tissues, providing potential mechanistic insights into how genetic variation might influence brain function and behavior .

• Statistical considerations: When conducting similar studies, researchers should employ appropriate statistical methods for quantitative trait analysis, considering factors such as data normality, skewness, and proper experimental design as outlined in standard quantitative analysis approaches .

What are the optimal methods for studying WSCD2 expression in different tissues?

When designing experiments to study WSCD2 expression across tissues, researchers should follow these methodological guidelines:

• Tissue selection: Since WSCD2 has been linked to personality traits and psychiatric conditions, including brain tissues is essential. Additionally, as the protein is predicted to localize to the Golgi membrane, cell types with prominent secretory functions may be particularly relevant .

• Expression quantification: Quantitative PCR (qPCR) for mRNA levels and Western blotting or immunohistochemistry for protein levels should be employed. For more comprehensive analysis, RNA-sequencing can provide detailed transcriptomic profiles.

• Experimental design considerations:

  • Define clear independent variables (e.g., tissue type, disease status) and dependent variables (e.g., WSCD2 expression levels)

  • Formulate specific, testable hypotheses about expression patterns

  • Ensure appropriate controls for tissue-specific factors

  • Consider within-subject or between-subject designs based on your research question

• Statistical analysis: When analyzing expression data, descriptive statistics should first be generated to understand data distribution (mean, median, standard deviation, skewness). The choice of inferential statistics should be based on data distribution and research questions, with parametric tests for normally distributed data and non-parametric alternatives for skewed distributions .

What are the challenges in producing recombinant WSCD2 protein for functional studies?

Producing recombinant WSCD2 presents several methodological challenges that researchers should address:

• Expression system selection: While the search results don't provide specific information about WSCD2 recombinant production, insights can be drawn from related proteins like Kremen-2 . Mammalian expression systems may be preferable for WSCD2 given its predicted Golgi localization and potential post-translational modifications.

• Protein solubility: As a protein with predicted membrane association, WSCD2 may present solubility challenges. Researchers might need to optimize expression conditions or consider fusion tags to enhance solubility.

• Functional verification: After production, verification of proper folding and activity is essential. Since WSCD2 is predicted to have sulfotransferase activity, developing appropriate enzymatic assays would be necessary to confirm functional integrity of the recombinant protein .

• Purification strategy: A multi-step purification process would likely be needed, potentially including affinity chromatography followed by size exclusion or ion exchange chromatography to achieve >95% purity, similar to standards for other recombinant proteins .

How should researchers analyze gene expression data for WSCD2 across different experimental conditions?

When analyzing WSCD2 expression data across experimental conditions, researchers should implement a structured analytical approach:

• Data preprocessing:

  • Normalize expression data appropriately (e.g., using housekeeping genes for qPCR or robust normalization methods for RNA-seq)

  • Check for outliers and assess data distribution

  • Transform data if necessary to meet statistical assumptions

• Descriptive statistics: Calculate key parameters including:

  • Mean and median expression levels

  • Standard deviation to assess variability

  • Skewness to evaluate distribution symmetry

• Statistical testing:

  • For comparing two conditions: t-tests (parametric) or Mann-Whitney U tests (non-parametric)

  • For multiple conditions: ANOVA or Kruskal-Wallis tests followed by appropriate post-hoc tests

  • Consider statistical power based on sample size and expected effect size

• Visualization methods:

  • Box plots or violin plots to display distribution of expression levels

  • Heat maps for showing patterns across multiple conditions or tissues

  • Correlation plots if examining relationships with other genes or phenotypes

What statistical approaches are appropriate for analyzing WSCD2 genetic associations with complex traits?

For analyzing WSCD2 genetic associations with complex traits, researchers should consider:

What methodological approaches should be used to investigate WSCD2's role in psychiatric disorders?

To investigate WSCD2's role in psychiatric disorders, researchers should employ a multi-faceted methodological approach:

• Genetic association studies:

  • Case-control designs comparing WSCD2 variant frequencies between psychiatric patients and controls

  • Family-based association tests to control for population stratification

  • Polygenic risk score analyses incorporating WSCD2 variants

• Functional genomics:

  • eQTL analysis to determine how WSCD2 variants affect gene expression in brain tissues

  • Epigenetic profiling to examine regulatory mechanisms

  • Single-cell sequencing to identify cell type-specific expression patterns

• Animal models:

  • Generate WSCD2 knockout or transgenic models to study behavioral phenotypes

  • Assess effects on relevant neurobiological pathways

  • Evaluate responses to pharmacological interventions

• Integration with clinical data:

  • Correlate WSCD2 variants with clinical symptoms, disease progression, and treatment response

  • Conduct longitudinal studies to examine temporal relationships

Current evidence suggests links between WSCD2 and temperament in bipolar disorder, warranting further investigation into specific mechanistic pathways .

How does WSCD2 relate to other genetic factors in Acne vulgaris pathogenesis?

WSCD2 has been identified in genome-wide association studies as a susceptibility locus for severe Acne vulgaris . Researchers investigating this connection should:

• Pathway analysis: Examine biological pathways connecting WSCD2 to known acne pathogenic mechanisms, such as sebum production, inflammation, or bacterial colonization.

• Gene-gene interaction studies: Investigate potential epistatic interactions between WSCD2 and other acne-associated genes.

• Tissue-specific expression: Analyze WSCD2 expression in relevant tissues such as sebaceous glands and compare expression patterns between affected and unaffected individuals.

• Functional studies: Design experiments to determine whether and how WSCD2 variants affect sebocyte function, inflammatory responses, or interactions with Cutibacterium acnes.

• Therapeutic implications: Assess whether WSCD2 or its associated pathways could represent novel therapeutic targets for severe acne treatment.

What emerging technologies would advance understanding of WSCD2 function?

Several cutting-edge technologies could significantly advance our understanding of WSCD2 function:

• CRISPR-Cas9 genome editing:

  • Generate precise WSCD2 mutations or knockout models in relevant cell lines

  • Create isogenic cell lines differing only in WSCD2 variants identified in GWAS

  • Develop knock-in models of human WSCD2 variants in model organisms

• Proteomics approaches:

  • Proximity labeling techniques to identify WSCD2 interaction partners

  • Mass spectrometry to characterize post-translational modifications

  • Structural biology methods (cryo-EM, X-ray crystallography) to determine WSCD2 structure

• Single-cell technologies:

  • Single-cell RNA-seq to map cell type-specific expression patterns

  • Spatial transcriptomics to understand WSCD2 expression in tissue context

  • Single-cell epigenomics to characterize regulatory mechanisms

• Systems biology integration:

  • Multi-omics data integration to place WSCD2 in broader biological networks

  • Machine learning approaches to predict functional impacts of WSCD2 variants

How might researchers investigate the evolutionary conservation of WSCD2 across species?

To investigate evolutionary aspects of WSCD2, researchers should employ comparative genomics approaches:

• Sequence conservation analysis:

  • Align WSCD2 orthologs across species ranging from primates to more distant vertebrates

  • Calculate conservation scores for different protein domains

  • Identify evolutionarily constrained regions that may indicate functional importance

• Synteny analysis:

  • Examine conservation of genomic context around WSCD2 across species

  • Identify conserved regulatory elements that might control WSCD2 expression

• Molecular evolution metrics:

  • Calculate dN/dS ratios to assess selective pressure on WSCD2

  • Identify signatures of positive, negative, or balancing selection

  • Determine whether WSCD2 shows accelerated evolution in specific lineages

• Functional divergence:

  • Compare expression patterns of WSCD2 orthologs across species

  • Test whether orthologs can functionally complement each other in experimental systems

• Correlation with species traits:

  • Investigate whether WSCD2 sequence or expression variation correlates with species-specific behavioral or physiological traits, particularly given its association with personality traits in humans