CIDeRplusGeneral Information:
| Id: | 9,161 |
| Diseases: |
Major depressive disorder
- [OMIM]
Neurological |
| Homo sapiens | |
| 306 MDD patients treated with citalopram or escitalopram | |
| article/cited | |
| Reference: | Gupta M et al.(2016) TSPAN5, ERICH3 and selective serotonin reuptake inhibitors in major depressive disorder: pharmacometabolomics-informed pharmacogenomics Mol. Psychiatry 21: 1717-1725 [PMID: 26903268] |
Interaction Information:
| Comment | Citalopram and escitalopram, used to treat MDD, are selective serotonin reuptake inhibitor (SSRI). |
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Formal Description Interaction-ID: 97042 |
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| Drugbank entries | Show/Hide entries for Citalopram |
| Comment | TSPAN5 and ERICH3 are associated with plasma serotonin concentrations and may have a role in SSRI (selective serotonin reuptake inhibitor) treatment outcomes. |
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Formal Description Interaction-ID: 97043 |
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| Comment | Citalopram and escitalopram, used to treat MDD, are selective serotonin reuptake inhibitor (SSRI). |
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Formal Description Interaction-ID: 97045 |
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| Drugbank entries | Show/Hide entries for Escitalopram |
| Comment | SSRI (citalopram and escitalopram) treatment decreased plasma serotonin concentrations significantly after 4 and 8 weeks of selective serotonin reuptake inhibitor treatment when compared with baseline. |
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Formal Description Interaction-ID: 97047 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Citalopram |
| Comment | TSPAN5 SNP (rs11947402) and ERICH3 nsSNP (rs11580409) account for 18.8% of the baseline variation of serotonin concentrations and 15.4% and 13% of the variation in the change in serotonin concentrations after 4 and 8 weeks of SSRI treatment in this MDD population, respectively. |
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Formal Description Interaction-ID: 97048 |
affects_quantity of drug/chemical compound |
| Comment | TSPAN5 knockdown in neuroblastoma cells was associated with a significant decrease in serotonin concentration in the cell culture media. These results indicated that the SNPs 5’ of TSPAN5 could influence its expression, which, in turn appeared to have a role in the regulation of serotonin-related pathways. TSPAN5 is a member of the tetraspanin superfamily, a family of proteins characterized by four hydrophobic transmembrane domains. Tetraspanins form molecular complexes within the plasma membrane that can modulate cellular signaling. |
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Formal Description Interaction-ID: 97050 |
phenotype decreased TSPAN5 level decreases_quantity of drug/chemical compound |
| Comment | Downregulation of Notch modulators, tetraspanin 5 and 10, inhibits osteoclastogenesis in vitro in mice. (cited information) |
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Formal Description Interaction-ID: 97055 |
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| Comment | Variant TSPAN5 SNP genotypes (rs11947402) were associated with higher baseline plasma serotonin concentrations and greater decreases in plasma serotonin concentration during SSRI therapy. Conversely, ERICH3 variant allele genotypes (rs696692, rs699848) were associated with lower baseline plasma serotonin concentrations and smaller decreases in plasma serotonin concentrations during SSRI therapy. The SNP most highly associated with baseline plasma serotonin concentration from this cluster was rs696692. The locus zoom for the genome-wide significant SNP cluster on chromosome 4 shows that the SNPs are approximately 15‚Äď25 kb 5‚Äô of TSPAN5, with rs11947402 as the most highly associated with baseline plasma serotonin concentration. |
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Formal Description Interaction-ID: 97062 |
affects_quantity of drug/chemical compound |
| Comment | The GTEx Database showed that brain displayed high expression for both TSPAN5 and ERICH3. Previous studies in mice had reported that the tissue with the highest TSPAN5 protein level was brain. (cited information) |
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Formal Description Interaction-ID: 97065 |
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| Comment | The rs11210490 SNP (Pro264Ala) was associated with a small (28%), but significant reduction in ERICH3 protein, while the rs11580409 SNP (Leu1056Val) was associated with an 80% decrease of ERICH protein. Constructs with both nsSNPs were associated with a 93% reduction in ERICH3 protein. |
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Formal Description Interaction-ID: 97067 |
decreases_quantity of gene/protein |
| Comment | When TSPAN5 was knocked down more than 70% in SK-N-BE(2) cells, there was a significant decrease of mRNA and protein levels for the serotonin pathway enzymes TPH1, TPH2, DDC, MAOA, as well as the serotonin transporter SLC6A4. |
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Formal Description Interaction-ID: 97070 |
phenotype decreased TSPAN5 level decreases_expression of gene/protein |
| Drugbank entries | Show/Hide entries for TPH1 |
| Comment | Overexpression of TSPAN5 was associated with increased expression of TPH1, TPH2, DDC and MAOA. Protein levels were not induced to the same extent as mRNA after TSPAN5 OE, perhaps because TSPAN5 is highly expressed in those cells. ERICH3 knockdown and overexpression did not alter the expression of serotonin pathway enzymes. |
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Formal Description Interaction-ID: 97071 |
phenotype increased TSPAN5 level increases_expression of gene/protein |
| Drugbank entries | Show/Hide entries for TPH1 |
| Comment | TSPAN5 has been reported to be involved in Notch signaling through ADAM10 recruitment and the Notch-Recombination Signal Binding Protein for Immunoglobulin Kappa J Region (RBPJ-kappa) has been implicated in regulation of the expression of serotonin pathway genes. |
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Formal Description Interaction-ID: 97072 |
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| Comment | TSPAN5 and ERICH3 are associated with plasma serotonin concentrations and may have a role in SSRI (selective serotonin reuptake inhibitor) treatment outcomes. |
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Formal Description Interaction-ID: 97074 |
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| Comment | SSRI (citalopram and escitalopram) treatment decreased plasma serotonin concentrations significantly after 4 and 8 weeks of selective serotonin reuptake inhibitor treatment when compared with baseline. |
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Formal Description Interaction-ID: 97076 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Escitalopram |
| Comment | TSPAN5 SNP (rs11947402) and ERICH3 nsSNP (rs11580409) account for 18.8% of the baseline variation of serotonin concentrations and 15.4% and 13% of the variation in the change in serotonin concentrations after 4 and 8 weeks of SSRI treatment in this MDD population, respectively. |
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Formal Description Interaction-ID: 97077 |
affects_quantity of drug/chemical compound |
| Comment | Downregulation of Notch modulators, tetraspanin 5 and 10, inhibits osteoclastogenesis in vitro in mice. (cited information) |
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Formal Description Interaction-ID: 97078 |
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| Comment | Downregulation of Notch modulators, tetraspanin 5 and 10, inhibits osteoclastogenesis in vitro in mice. (cited information) |
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Formal Description Interaction-ID: 97079 |
phenotype decreased TSPAN10 expression decreases_activity of process |
| Comment | Downregulation of Notch modulators, tetraspanin 5 and 10, inhibits osteoclastogenesis in vitro in mice. (cited information) |
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Formal Description Interaction-ID: 97080 |
phenotype decreased TSPAN5 expression decreases_activity of process |
| Comment | Variant TSPAN5 SNP genotypes (rs11947402) were associated with higher baseline plasma serotonin concentrations and greater decreases in plasma serotonin concentration during SSRI therapy. Conversely, ERICH3 variant allele genotypes (rs696692, rs699848) were associated with lower baseline plasma serotonin concentrations and smaller decreases in plasma serotonin concentrations during SSRI therapy. The SNP most highly associated with baseline plasma serotonin concentration from this cluster was rs696692. The locus zoom for the genome-wide significant SNP cluster on chromosome 4 shows that the SNPs are approximately 15‚Äď25 kb 5‚Äô of TSPAN5, with rs11947402 as the most highly associated with baseline plasma serotonin concentration. |
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Formal Description Interaction-ID: 97081 |
affects_activity of drug/chemical compound SSRI |
| Comment | Citalopram and escitalopram, used to treat MDD, are selective serotonin reuptake inhibitor (SSRI). |
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Formal Description Interaction-ID: 97082 |
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| Drugbank entries | Show/Hide entries for Escitalopram |
| Comment | Citalopram and escitalopram, used to treat MDD, are selective serotonin reuptake inhibitor (SSRI). |
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Formal Description Interaction-ID: 97083 |
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| Drugbank entries | Show/Hide entries for Citalopram |
| Comment | Variant TSPAN5 SNP genotypes (rs11947402) were associated with higher baseline plasma serotonin concentrations and greater decreases in plasma serotonin concentration during SSRI therapy. Conversely, ERICH3 variant allele genotypes (rs696692, rs699848) were associated with lower baseline plasma serotonin concentrations and smaller decreases in plasma serotonin concentrations during SSRI therapy. The SNP most highly associated with baseline plasma serotonin concentration from this cluster was rs696692. The locus zoom for the genome-wide significant SNP cluster on chromosome 4 shows that the SNPs are approximately 15‚Äď25 kb 5‚Äô of TSPAN5, with rs11947402 as the most highly associated with baseline plasma serotonin concentration. |
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Formal Description Interaction-ID: 97084 |
SNP affects_quantity of drug/chemical compound |
| Comment | Variant TSPAN5 SNP genotypes (rs11947402) were associated with higher baseline plasma serotonin concentrations and greater decreases in plasma serotonin concentration during SSRI therapy. Conversely, ERICH3 variant allele genotypes (rs696692, rs699848) were associated with lower baseline plasma serotonin concentrations and smaller decreases in plasma serotonin concentrations during SSRI therapy. The SNP most highly associated with baseline plasma serotonin concentration from this cluster was rs696692. The locus zoom for the genome-wide significant SNP cluster on chromosome 4 shows that the SNPs are approximately 15‚Äď25 kb 5‚Äô of TSPAN5, with rs11947402 as the most highly associated with baseline plasma serotonin concentration. |
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Formal Description Interaction-ID: 97085 |
SNP affects_quantity of drug/chemical compound |
| Comment | Variant TSPAN5 SNP genotypes (rs11947402) were associated with higher baseline plasma serotonin concentrations and greater decreases in plasma serotonin concentration during SSRI therapy. Conversely, ERICH3 variant allele genotypes (rs696692, rs699848) were associated with lower baseline plasma serotonin concentrations and smaller decreases in plasma serotonin concentrations during SSRI therapy. The SNP most highly associated with baseline plasma serotonin concentration from this cluster was rs696692. The locus zoom for the genome-wide significant SNP cluster on chromosome 4 shows that the SNPs are approximately 15‚Äď25 kb 5‚Äô of TSPAN5, with rs11947402 as the most highly associated with baseline plasma serotonin concentration. |
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Formal Description Interaction-ID: 97086 |
SNP affects_activity of drug/chemical compound SSRI |
| Comment | Variant TSPAN5 SNP genotypes (rs11947402) were associated with higher baseline plasma serotonin concentrations and greater decreases in plasma serotonin concentration during SSRI therapy. Conversely, ERICH3 variant allele genotypes (rs696692, rs699848) were associated with lower baseline plasma serotonin concentrations and smaller decreases in plasma serotonin concentrations during SSRI therapy. The SNP most highly associated with baseline plasma serotonin concentration from this cluster was rs696692. The locus zoom for the genome-wide significant SNP cluster on chromosome 4 shows that the SNPs are approximately 15‚Äď25 kb 5‚Äô of TSPAN5, with rs11947402 as the most highly associated with baseline plasma serotonin concentration. |
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Formal Description Interaction-ID: 97087 |
SNP affects_activity of drug/chemical compound SSRI |
| Comment | The GTEx Database showed that brain displayed high expression for both TSPAN5 and ERICH3. Previous studies in mice had reported that the tissue with the highest TSPAN5 protein level was brain. (cited information) |
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Formal Description Interaction-ID: 97088 |
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| Comment | TSPAN5 SNP (rs11947402) and ERICH3 nsSNP (rs11580409) account for 18.8% of the baseline variation of serotonin concentrations and 15.4% and 13% of the variation in the change in serotonin concentrations after 4 and 8 weeks of SSRI treatment in this MDD population, respectively. |
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Formal Description Interaction-ID: 97089 |
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| Comment | Variant TSPAN5 SNP genotypes (rs11947402) were associated with higher baseline plasma serotonin concentrations and greater decreases in plasma serotonin concentration during SSRI therapy. Conversely, ERICH3 variant allele genotypes (rs696692, rs699848) were associated with lower baseline plasma serotonin concentrations and smaller decreases in plasma serotonin concentrations during SSRI therapy. The SNP most highly associated with baseline plasma serotonin concentration from this cluster was rs696692. The locus zoom for the genome-wide significant SNP cluster on chromosome 4 shows that the SNPs are approximately 15‚Äď25 kb 5‚Äô of TSPAN5, with rs11947402 as the most highly associated with baseline plasma serotonin concentration. |
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Formal Description Interaction-ID: 97090 |
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| Comment | Variant TSPAN5 SNP genotypes (rs11947402) were associated with higher baseline plasma serotonin concentrations and greater decreases in plasma serotonin concentration during SSRI therapy. Conversely, ERICH3 variant allele genotypes (rs696692, rs699848) were associated with lower baseline plasma serotonin concentrations and smaller decreases in plasma serotonin concentrations during SSRI therapy. The SNP most highly associated with baseline plasma serotonin concentration from this cluster was rs696692. The locus zoom for the genome-wide significant SNP cluster on chromosome 4 shows that the SNPs are approximately 15‚Äď25 kb 5‚Äô of TSPAN5, with rs11947402 as the most highly associated with baseline plasma serotonin concentration. |
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Formal Description Interaction-ID: 97091 |
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| Comment | Variant TSPAN5 SNP genotypes (rs11947402) were associated with higher baseline plasma serotonin concentrations and greater decreases in plasma serotonin concentration during SSRI therapy. Conversely, ERICH3 variant allele genotypes (rs696692, rs699848) were associated with lower baseline plasma serotonin concentrations and smaller decreases in plasma serotonin concentrations during SSRI therapy. The SNP most highly associated with baseline plasma serotonin concentration from this cluster was rs696692. The locus zoom for the genome-wide significant SNP cluster on chromosome 4 shows that the SNPs are approximately 15‚Äď25 kb 5‚Äô of TSPAN5, with rs11947402 as the most highly associated with baseline plasma serotonin concentration. |
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Formal Description Interaction-ID: 97092 |
drug/chemical compound SSRI affects_quantity of drug/chemical compound |
| Comment | The rs11210490 SNP (Pro264Ala) was associated with a small (28%), but significant reduction in ERICH3 protein, while the rs11580409 SNP (Leu1056Val) was associated with an 80% decrease of ERICH protein. Constructs with both nsSNPs were associated with a 93% reduction in ERICH3 protein. |
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Formal Description Interaction-ID: 97093 |
decreases_quantity of gene/protein |
| Comment | When TSPAN5 was knocked down more than 70% in SK-N-BE(2) cells, there was a significant decrease of mRNA and protein levels for the serotonin pathway enzymes TPH1, TPH2, DDC, MAOA, as well as the serotonin transporter SLC6A4. |
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Formal Description Interaction-ID: 97094 |
phenotype decreased TSPAN5 level decreases_expression of gene/protein |
| Comment | When TSPAN5 was knocked down more than 70% in SK-N-BE(2) cells, there was a significant decrease of mRNA and protein levels for the serotonin pathway enzymes TPH1, TPH2, DDC, MAOA, as well as the serotonin transporter SLC6A4. |
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Formal Description Interaction-ID: 97095 |
phenotype decreased TSPAN5 level decreases_expression of gene/protein |
| Drugbank entries | Show/Hide entries for DDC |
| Comment | When TSPAN5 was knocked down more than 70% in SK-N-BE(2) cells, there was a significant decrease of mRNA and protein levels for the serotonin pathway enzymes TPH1, TPH2, DDC, MAOA, as well as the serotonin transporter SLC6A4. |
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Formal Description Interaction-ID: 97096 |
phenotype decreased TSPAN5 level decreases_expression of gene/protein |
| Drugbank entries | Show/Hide entries for MAOA |
| Comment | When TSPAN5 was knocked down more than 70% in SK-N-BE(2) cells, there was a significant decrease of mRNA and protein levels for the serotonin pathway enzymes TPH1, TPH2, DDC, MAOA, as well as the serotonin transporter SLC6A4. |
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Formal Description Interaction-ID: 97097 |
phenotype decreased TSPAN5 level decreases_expression of gene/protein |
| Drugbank entries | Show/Hide entries for SLC6A4 |
| Comment | Overexpression of TSPAN5 was associated with increased expression of TPH1, TPH2, DDC and MAOA. Protein levels were not induced to the same extent as mRNA after TSPAN5 OE, perhaps because TSPAN5 is highly expressed in those cells. ERICH3 knockdown and overexpression did not alter the expression of serotonin pathway enzymes. |
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Formal Description Interaction-ID: 97098 |
phenotype increased TSPAN5 level increases_expression of gene/protein |
| Comment | Overexpression of TSPAN5 was associated with increased expression of TPH1, TPH2, DDC and MAOA. Protein levels were not induced to the same extent as mRNA after TSPAN5 OE, perhaps because TSPAN5 is highly expressed in those cells. ERICH3 knockdown and overexpression did not alter the expression of serotonin pathway enzymes. |
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Formal Description Interaction-ID: 97099 |
phenotype increased TSPAN5 level increases_expression of gene/protein |
| Drugbank entries | Show/Hide entries for DDC |
| Comment | Overexpression of TSPAN5 was associated with increased expression of TPH1, TPH2, DDC and MAOA. Protein levels were not induced to the same extent as mRNA after TSPAN5 OE, perhaps because TSPAN5 is highly expressed in those cells. ERICH3 knockdown and overexpression did not alter the expression of serotonin pathway enzymes. |
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Formal Description Interaction-ID: 97100 |
phenotype increased TSPAN5 level increases_expression of gene/protein |
| Drugbank entries | Show/Hide entries for MAOA |
| Comment | Overexpression of TSPAN5 was associated with increased expression of TPH1, TPH2, DDC and MAOA. Protein levels were not induced to the same extent as mRNA after TSPAN5 OE, perhaps because TSPAN5 is highly expressed in those cells. ERICH3 knockdown and overexpression did not alter the expression of serotonin pathway enzymes. |
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Formal Description Interaction-ID: 97101 |
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| Drugbank entries | Show/Hide entries for TPH1 |
| Comment | Overexpression of TSPAN5 was associated with increased expression of TPH1, TPH2, DDC and MAOA. Protein levels were not induced to the same extent as mRNA after TSPAN5 OE, perhaps because TSPAN5 is highly expressed in those cells. ERICH3 knockdown and overexpression did not alter the expression of serotonin pathway enzymes. |
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Formal Description Interaction-ID: 97102 |
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| Comment | Overexpression of TSPAN5 was associated with increased expression of TPH1, TPH2, DDC and MAOA. Protein levels were not induced to the same extent as mRNA after TSPAN5 OE, perhaps because TSPAN5 is highly expressed in those cells. ERICH3 knockdown and overexpression did not alter the expression of serotonin pathway enzymes. |
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Formal Description Interaction-ID: 97103 |
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| Drugbank entries | Show/Hide entries for DDC |
| Comment | Overexpression of TSPAN5 was associated with increased expression of TPH1, TPH2, DDC and MAOA. Protein levels were not induced to the same extent as mRNA after TSPAN5 OE, perhaps because TSPAN5 is highly expressed in those cells. ERICH3 knockdown and overexpression did not alter the expression of serotonin pathway enzymes. |
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Formal Description Interaction-ID: 97104 |
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| Drugbank entries | Show/Hide entries for MAOA |
| Comment | TSPAN5 has been reported to be involved in Notch signaling through ADAM10 recruitment and the Notch-Recombination Signal Binding Protein for Immunoglobulin Kappa J Region (RBPJ-kappa) has been implicated in regulation of the expression of serotonin pathway genes. |
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Formal Description Interaction-ID: 97105 |
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| Comment | TSPAN5 has been reported to be involved in Notch signaling through ADAM10 recruitment and the Notch-Recombination Signal Binding Protein for Immunoglobulin Kappa J Region (RBPJ-kappa) has been implicated in regulation of the expression of serotonin pathway genes. |
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Formal Description Interaction-ID: 97266 |
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| Comment | Knocked down RBPJ-kappa in SK-N-BE(2) cells increased expression of TPH1, TPH2, DDC and SLC6A4. |
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Formal Description Interaction-ID: 97267 |
phenotype decreased RBPJ level increases_expression of gene/protein |
| Drugbank entries | Show/Hide entries for TPH1 |
| Comment | Knocked down RBPJ-kappa in SK-N-BE(2) cells increased expression of TPH1, TPH2, DDC and SLC6A4. |
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Formal Description Interaction-ID: 97268 |
phenotype decreased RBPJ level increases_expression of gene/protein |
| Comment | Knocked down RBPJ-kappa in SK-N-BE(2) cells increased expression of TPH1, TPH2, DDC and SLC6A4. |
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Formal Description Interaction-ID: 97269 |
phenotype decreased RBPJ level increases_expression of gene/protein |
| Drugbank entries | Show/Hide entries for DDC |
| Comment | Knocked down RBPJ-kappa in SK-N-BE(2) cells increased expression of TPH1, TPH2, DDC and SLC6A4. |
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Formal Description Interaction-ID: 97270 |
phenotype decreased RBPJ level increases_expression of gene/protein |
| Drugbank entries | Show/Hide entries for SLC6A4 |
| Comment | Variant TSPAN5 SNP genotypes (rs11947402) were associated with higher baseline plasma serotonin concentrations and greater decreases in plasma serotonin concentration during SSRI therapy. Conversely, ERICH3 variant allele genotypes (rs696692, rs699848) were associated with lower baseline plasma serotonin concentrations and smaller decreases in plasma serotonin concentrations during SSRI therapy. The SNP most highly associated with baseline plasma serotonin concentration from this cluster was rs696692. The locus zoom for the genome-wide significant SNP cluster on chromosome 4 shows that the SNPs are approximately 15‚Äď25 kb 5‚Äô of TSPAN5, with rs11947402 as the most highly associated with baseline plasma serotonin concentration. |
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Formal Description Interaction-ID: 98329 |
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| Comment | When TSPAN5 was knocked down more than 70% in SK-N-BE(2) cells, there was a significant decrease of mRNA and protein levels for the serotonin pathway enzymes TPH1, TPH2, DDC, MAOA, as well as the serotonin transporter SLC6A4. |
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Formal Description Interaction-ID: 136239 |
phenotype decreased TSPAN5 level decreases_quantity of gene/protein |
| Drugbank entries | Show/Hide entries for TPH1 |
| Comment | When TSPAN5 was knocked down more than 70% in SK-N-BE(2) cells, there was a significant decrease of mRNA and protein levels for the serotonin pathway enzymes TPH1, TPH2, DDC, MAOA, as well as the serotonin transporter SLC6A4. |
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Formal Description Interaction-ID: 136240 |
phenotype decreased TSPAN5 level decreases_quantity of gene/protein |
| Comment | When TSPAN5 was knocked down more than 70% in SK-N-BE(2) cells, there was a significant decrease of mRNA and protein levels for the serotonin pathway enzymes TPH1, TPH2, DDC, MAOA, as well as the serotonin transporter SLC6A4. |
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Formal Description Interaction-ID: 136241 |
phenotype decreased TSPAN5 level decreases_quantity of gene/protein |
| Drugbank entries | Show/Hide entries for DDC |
| Comment | When TSPAN5 was knocked down more than 70% in SK-N-BE(2) cells, there was a significant decrease of mRNA and protein levels for the serotonin pathway enzymes TPH1, TPH2, DDC, MAOA, as well as the serotonin transporter SLC6A4. |
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Formal Description Interaction-ID: 136242 |
phenotype decreased TSPAN5 level decreases_quantity of gene/protein |
| Drugbank entries | Show/Hide entries for MAOA |
| Comment | When TSPAN5 was knocked down more than 70% in SK-N-BE(2) cells, there was a significant decrease of mRNA and protein levels for the serotonin pathway enzymes TPH1, TPH2, DDC, MAOA, as well as the serotonin transporter SLC6A4. |
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Formal Description Interaction-ID: 136243 |
phenotype decreased TSPAN5 level decreases_quantity of gene/protein |
| Drugbank entries | Show/Hide entries for SLC6A4 |