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Gene & Protein in Disease Regulatory elements of ATP7B in WD

A

B

Figure 3. Allele-specific transcription factor binding alteration and gene expression of rs2181891. (A) Interpretation of RegulomeDB score from UCSC
genome browser. The red line signifies the locus of the SNP. It is located within a DNase I Hypersensitive site containing an H3K27Ac mark, indicating
an enhancer region. The SNP likely affects the transcription factor binding. The regulatory potential of this SNP has been validated in the GM12878
lymphoblastoid cell line. (B) The genotype-specific expression of rs2181891 was validated in hepatic and neuronal tissues from the GTEx portal. The
rs2181891 (T/G) polymorphism acts as an eQTL in brain cerebellum tissue.
Abbreviations: eQTL: Expression quantitative trait loci; GTEx: Genotype-Tissue Expression; Norm.: Normalized; SNP: Single nucleotide polymorphism;
UCSC: University of California, Santa Cruz.

4. Conclusion Our analysis was limited to screening only three cis-
regulatory elements for ATP7B. As noted in our recent
In this study, no potential pathogenic variant in the cis- review, screening additional cis-regulatory elements and
regulatory elements of ATP7B that could explain the deep intronic regions of ATP7B may provide insights into
uncharacterized mutations in the Indian WD patients identifying the mutations responsible for WD. Whole
was identified. However, a potentially regulatory exome sequencing can be conducted to uncover the missing
SNP, rs2181891, was identified as heterozygous in heritability for WD. Therefore, a comprehensive strategy
two WD patients. Although this G/T polymorphism beyond screening the ATP7B coding region is necessary to
shows strong regulatory potential, as indicated by a identify the causal variants for WD and resolve the paradox
RegulomeDB score of 1d, the eQTL effects of this SNP of missing heritability associated with the disease.
were observed only in cerebellum tissue. According
to GTEx data, the variant allele (T) is associated with Acknowledgments
higher expression of ATP7B, which is unlikely to We are thankful to the WD patients and their family
contribute to WD. members for participating in this study. We also

Volume 4 Issue 2 (2025) 6 doi: 10.36922/gpd.7503