In Silico Analysis of Post-COVID-19 Condition (PCC) Associated SNP rs9367106 Predicts the Molecular Basis of Abnormalities in the Lungs and Brain Functions
Abstract
1. Introduction
2. Results
2.1. The rs9367106 Resides Within the Long Noncoding RNAs, LINC01276 and AS-FOXP4 and Physically Interacts with the Coding FOXP4 Gene
2.2. The G>C Transition of rs9367106 Extensively Alters the RNA Structure
2.3. The rs9367106 Disrupts an ALU/SINE Element
2.4. rs9367106 Carrying DNA Region Binds with Several Transcription Factors (TFs)
2.5. rs9367106 Affects the Expression of FOXP4 and MED20 Genes
2.6. The SNP-Carrying RNA Region Acts as a Distant Enhancer
2.7. The LINC01276 Targets the MED20 Gene That Extensively Expresses Tissues in the Brain and Modulates Sleep Disorder
2.8. FOXP4-AS1 Function
2.9. FOXP4 Could Alter the Functions of Lung Alveolar Cells and Brain Tissues Leading to PCC Phenotypes
2.10. rs9367106 Co-Expressed Genes Induce FOXP4-FOXP2 and TP63 Enriched Pathway
3. Discussion
Limitation
4. Materials and Methods
4.1. Physical Interaction
4.2. eQTL Analysis
4.3. Expression
4.4. Enhancer Analysis
4.5. Transcription Factor Binding Sites
4.6. RNA Structure Modeling
4.7. ALU/SINE Sequence Identification
4.8. LINC01276 Target Identification
4.9. Co-Expression, Gene and Pathway Enrichment
Supplementary Materials
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Contact Domain (TADs) | ||||||||||
Cells | Methods | Built | Chr | 1st Chr | 1st Chr | Chr | 2nd Chr | 2nd Chr | Experiments/ Database | |
h1ESC | Mi-C | Hg19 | 6 | 41,335,000 | 41,565,000 | 6 | 41,335,000 | 41,565,000 | [17] | |
hff6 | Mi-C | Hg19 | 6 | 41,330,000 | 41,565,000 | 6 | 41,330,000 | 41,565,000 | [17] | |
GM12987 | Hi-C | HG19 | 6 | 41,390,000 | 41,560,000 | 6 | 41,390,000 | 41,560,000 | [18] | |
K662 | Hi-C | Hg19 | 6 | 41,430,000 | 41,440,000 | 6 | 41,540,000 | 41,550,000 | [18] | |
Loop | ||||||||||
h1ESC | Mi-C | Hg19 | 6 | 41,335,000 | 41,340,000 | 6 | 41,650,000 | 41,655,000 | [17] | |
K562 | Hi-C | Hg19 | 6 | 41,330,000 | 41,340,000 | 6 | 41,560,000 | 41,570,000 | [18] | |
K562 | Hi-C | Hg19 | 6 | 41,430,000 | 41,440,000 | 6 | 41,540,000 | 41,550,000 | [18] | |
GM12978 | Hi-C | Hg19 | 6 | 41,330,000 | 41,565,000 | 6 | 41,330,000 | 41,565,000 | [20] | |
GM12978 | Hi-C | Hg19 | 6 | 41,430,934 | 41,440,274 | 6 | 41,532,231 | 41,533,943 | [19] | |
GM12978 | Hi-C | Hg19 | 6 | 41,430,934 | 41,440,274 | 6 | 41,549,065 | 41,559,381 | [19] | |
IMR90 | Hi-C | Hg19 | 6 | 41,332,022 | 41,692,022 | 6 | 41,332,022 | 41,692,022 | [21] | |
K562 | CTCF/Chia-pet | Hg19 | 6 | 41,335,405 | 41,335,912 | 6 | 41,430,559 | 41,431,171 | [22] | |
K562 | CTCF/Chia-pet | Hg19 | 6 | 41,431,132 | 41,431,741 | 6 | 41,651,489 | 41,652,021 | [22] | |
K562 | Hi-C | Hg19 | 6 | 41,437,792 | 41,441,855 | 6 | 41,442,012 | 41,447,536 | [23] | |
K562 | Hi-C | Hg19 | 6 | 41,472,346 | 41,533,996 | 6 | 41,480,511 | 41,550,119 | [23] | |
Peak | ||||||||||
h1ESC | Mi-C | Hg19 | 6 | 41,465,000 | 41,470,000 | 6 | 41,515,000 | 41,520,000 | [17] | |
hFF6 | Mi-C | Hg19 | 6 | 41,390,000 | 41,395,000 | 6 | 41,555,000 | 41,560,000 | [17] |
Hg19 | |||
---|---|---|---|
START Region | END Region | Gene | Gene Start/End |
chr6:41,480,772–41,483,123 | chr6:41,559,468–41,562,360 | FOXP4/FOXP4-AS1 | chr6:41,514,164–41,570,122/chr6:41,462,591–41,516,359 |
chr6:41,480,772–41,483,123 | chr6:41,559,468–41,562,360 | FOXP4/FOXP4-AS1 | chr6:41,514,164–41,570,122/chr6:41,462,591–41,516,359 |
chr6:41,482,545–41,484,504 | chr6:41,491,670–41,493,377 | FOXP4/FOXP4-AS1 | chr6:41,514,164–41,570,122/chr6:41,462,591–41,516,359 |
chr6:41,482,796–41,484,928 | chr6:41,485,202–41,488,839 | FOXP4/FOXP4-AS1 | chr6:41,514,164–41,570,122/chr6:41,462,591–41,516,359 |
chr6:41,487,810–41,489,374 | chr6:41,507,169–41,508,917 | FOXP4/FOXP4-AS1 | chr6:41,514,164–41,570,122/chr6:41,462,591–41,516,359 |
chr6:41,489,724–41,492,551 | chr6:41,509,027–41,511,261 | FOXP4/FOXP4-AS1 | chr6:41,514,164–41,570,122/chr6:41,462,591–41,516,359 |
chr6:41,482,545–41,484,504 | chr6:41,491,670–41,493,377 | FOXP4/FOXP4-AS1 | chr6:41,514,164–41,570,122/chr6:41,462,591–41,516,359 |
chr6:41,488,184–41,490,839 | chr6:41,494,174–41,495,933 | FOXP4/FOXP4-AS1 | chr6:41,514,164–41,570,122/chr6:41,462,591–41,516,359 |
chr6:41,482,796–41,484,928 | chr6:41,485,202–41,488,839 | FOXP4/FOXP4-AS1 | chr6:41,514,164–41,570,122/chr6:41,462,591–41,516,359 |
chr6:41,482,796–41,484,928 | chr6:41,485,202–41,488,839 | FOXP4/FOXP4-AS1 | chr6:41,514,164–41,570,122/chr6:41,462,591–41,516,359 |
chr6:41,482,545–41,484,504 | chr6:41,491,670–41,493,377 | FOXP4/FOXP4-AS1 | chr6:41,514,164–41,570,122/chr6:41,462,591–41,516,359 |
chr6:41,488,184–41,490,839 | chr6:41,494,174–41,495,933 | FOXP4/FOXP4-AS1 | chr6:41,514,164–41,570,122/chr6:41,462,591–41,516,359 |
chr6:41,478,170–41,480,141 | chr6:41,497,521–41,499,884 | FOXP4/FOXP4-AS1 | chr6:41,514,164–41,570,122/chr6:41,462,591–41,516,359 |
chr6:41,482,545–41,484,504 | chr6:41,491,670–41,493,377 | FOXP4/FOXP4-AS1 | chr6:41,514,164–41,570,122/chr6:41,462,591–41,516,359 |
Hg19 | ||||||
---|---|---|---|---|---|---|
START Region | Gene | END Region | Gene | Method | Cells | Attached Antibody |
chr6:41,474,351–41,477,033 | rs9367106/LINC01276 (chr6:41,470,182–41,487,590) | chr:41,484,872–41,500,890 | MED20 (chr6:41,873,092–41,888,877) | Hi-C | IMR90 | NA |
chr6:41,464,534–41,475,625 | rs9367106/LINC01276 (chr6:41,470,182–41,487,590) | chr:41,484,872–41,488,927 | MED20 (chr6:41,873,092–41,888,877) | Hi-C | IMR90 | NA |
chr6:41,482,503–41,486,148 | rs9367106/LINC01276 (chr6:41,470,182–41,487,590) | chr6:41,512,979–4,151,495 | MED20 (chr6:41,873,092–41,888,877) | Chia-PET | K562 | POL2RA |
chr6:41,437,907–41,440,085 | rs9367106/LINC01276 (chr6:41,470,182–41,487,590) | chr6:41,484,931–41,487,417 | MED20 (chr6:41,873,092–41,888,877) | Chia-PET | MCF7 | POL2RA |
chr6:41,482,503–41,486,148 | rs9367106/LINC01276 (chr6:41,470,182–41,487,590) | chr6:41,512,979–41,514,951 | MED20 (chr6:41,873,092–41,888,877) | Chia-PET | MCF7 | POL2RA |
chr6:41,472,346–41,533,996 | rs9367106/LINC01276 (chr6:41,470,182–41,487,590) | chr6:41,480,511–41,550,119 | MED20 (chr6:41,873,092–41,888,877) | Chia-PET | K562 | POL2RA |
Region | Australia | |||
Ethnicity | No ethnicity reported | |||
Co-morbidities | Not reported | |||
Age | Matched (~equivalent) | |||
Disease severity | N | Male | Female | Clinical symptoms |
Healthy subjects | 14 | 7 | 7 | no known significant systemic diseases, and negative anti-Spike and anti-RBD serology |
Mild | 50 | 26 | 24 | COVID-19 disease severity was scored as per CDC descriptors (https://www.cdc.gov/covid/hcp/clinical-care/management-and-treatment.html (accessed on 6 July 2025)) |
Moderate | 6 | 2 | 4 | “ |
Severe | 7 | 5 | 2 | “ |
Critical | 6 | 3 | 3 | “ |
Total | 83 | 43 | 40 |
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Maiti, A.K. In Silico Analysis of Post-COVID-19 Condition (PCC) Associated SNP rs9367106 Predicts the Molecular Basis of Abnormalities in the Lungs and Brain Functions. Int. J. Mol. Sci. 2025, 26, 6680. https://doi.org/10.3390/ijms26146680
Maiti AK. In Silico Analysis of Post-COVID-19 Condition (PCC) Associated SNP rs9367106 Predicts the Molecular Basis of Abnormalities in the Lungs and Brain Functions. International Journal of Molecular Sciences. 2025; 26(14):6680. https://doi.org/10.3390/ijms26146680
Chicago/Turabian StyleMaiti, Amit K. 2025. "In Silico Analysis of Post-COVID-19 Condition (PCC) Associated SNP rs9367106 Predicts the Molecular Basis of Abnormalities in the Lungs and Brain Functions" International Journal of Molecular Sciences 26, no. 14: 6680. https://doi.org/10.3390/ijms26146680
APA StyleMaiti, A. K. (2025). In Silico Analysis of Post-COVID-19 Condition (PCC) Associated SNP rs9367106 Predicts the Molecular Basis of Abnormalities in the Lungs and Brain Functions. International Journal of Molecular Sciences, 26(14), 6680. https://doi.org/10.3390/ijms26146680