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ABCB11

receptor: FXRTier 1
Prior gene annotation

Retained explanatory context, not the pharmacist's submitted wording; submitted reviews below take precedence.

Drug substrates (prior annotation)

bosentan; cyclosporine; estrogens

refs: 11870371, 25198545

CAMIP Tier 1: peak-anchored panel

FXR

Submitted decision (verbatim): 需修訂

Reviewer revision (verbatim)

Reduced FXR/RXRα binding impairs receptor-mediated transactivation of ABCB11, reducing BSEP expression and thereby limiting adaptive increases in canalicular ATP-dependent bile salt export. Under increased bile salt load, this impaired inducibility may promote intracellular bile salt accumulation and increase susceptibility to drug-induced cholestatic liver injury.
Prior explanatory context

Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.

Inducer
Obeticholic acid; Experimental GW4064
Regulatory element
overlapping TSS
Predicted consequence
Disrupted receptor-mediated transactivation via the FXR/RXRα heterodimer, abolishing the critical canalicular expression of the Bile Salt Export Pump. This directly cripples the ATP-dependent rate-limiting step of hepatic bile acid elimination, precipitating toxic intracellular bile salt accumulation and rendering hepatocytes profoundly vulnerable to severe drug-induced cholestatic liver injury under medications such as bosentan and cyclosporine.
Prior narrative
Disrupted receptor-mediated transactivation via the FXR/RXRα heterodimer, abolishing the critical canalicular expression of the Bile Salt Export Pump. This directly cripples the ATP-dependent rate-limiting step of hepatic bile acid elimination, precipitating toxic intracellular bile salt accumulation and rendering hepatocytes profoundly vulnerable to severe drug-induced cholestatic liver injury under medications such as bosentan and cyclosporine.
Drug context
bosentan; cyclosporine; estrogens
Prior references
11870371, 25198545

Scored variants near ABCB11

chr2:168,820,780..169,131,324, gene body plus 100 kb. Showing the strongest 200 by effect size.

Variant Position PXR FXR AhR AF
chr2_169031334_A_Gchr2:1690313341.0001.0000.959—   
chr2_169031340_A_Gchr2:1690313401.0001.0000.953—   
chr2_169031312_T_Achr2:1690313120.5811.0001.000—   
chr2_169031342_T_Cchr2:1690313420.8200.9850.747—   
chr2_169031312_T_Gchr2:1690313120.5090.9151.000—   
chr2_169031317_A_Gchr2:1690313170.5490.7230.482—   
chr2_169031343_C_Gchr2:1690313430.4910.5430.556—   
chr2_169031315_T_Gchr2:1690313150.4680.7510.694—   
chr2_169031224_C_Gchr2:169031224-0.409-0.602-0.618—   
chr2_169031254_G_Tchr2:1690312540.4080.4850.288—   
chr2_169031341_T_Gchr2:1690313410.4080.6090.318—   
chr2_169031224_C_Achr2:169031224-0.404-0.580-0.662—   
chr2_169031223_A_Cchr2:169031223-0.363-0.508-0.671—   
chr2_169031326_A_Tchr2:169031326-0.374-0.546-0.529—   
chr2_169031282_A_Cchr2:1690312820.3660.5610.300—   
chr2_169031338_G_Tchr2:169031338-0.359-0.548-0.412—   
chr2_169031225_C_Achr2:169031225-0.353-0.503-0.456—   
chr2_169031223_A_Tchr2:169031223-0.351-0.472-0.600—   
chr2_169031288_T_Cchr2:169031288-0.279-0.491-0.612—   
chr2_169031308_T_Cchr2:1690313080.3440.4920.318—   
chr2_169031288_T_Achr2:169031288-0.286-0.475-0.597—   
chr2_169031290_T_Cchr2:169031290-0.333-0.645-0.506—   
chr2_169031315_T_Cchr2:169031315-0.329-0.503-0.538—   
chr2_169031314_T_Cchr2:169031314-0.317-0.518-0.453—   
chr2_169031312_T_Cchr2:1690313120.3070.4180.506—   
chr2_169031295_A_Tchr2:169031295-0.196-0.322-0.509—   
chr2_169031313_T_Cchr2:169031313-0.271-0.426-0.506—   
chr2_169031224_C_Tchr2:169031224-0.285-0.475-0.482—   
chr2_169031292_A_Gchr2:1690312920.2780.5510.429—   
chr2_169031294_A_Tchr2:169031294-0.210-0.487-0.488—   
chr2_169031336_C_Gchr2:169031336-0.271-0.346-0.474—   
chr2_169031338_G_Achr2:169031338-0.269-0.358-0.265—   
chr2_169031291_C_Tchr2:169031291-0.225-0.429-0.471—   
chr2_169031289_T_Achr2:169031289-0.218-0.462-0.462—   
chr2_169031302_C_Gchr2:1690313020.2600.5130.418—   
chr2_169031336_C_Achr2:169031336-0.223-0.227-0.447—   
chr2_169031262_G_Cchr2:1690312620.2460.2720.235—   
chr2_169031223_A_Gchr2:169031223-0.245-0.350-0.397—   
chr2_169031194_G_Cchr2:1690311940.2430.2560.156—   
chr2_169031308_T_Gchr2:1690313080.2430.4470.406—   
chr2_169031340_A_Tchr2:1690313400.2430.2820.288—   
chr2_169031296_C_Achr2:169031296-0.150-0.308-0.426—   
chr2_169031254_G_Cchr2:1690312540.2400.2770.176—   
chr2_169031334_A_Tchr2:169031334-0.235-0.322-0.288—   
chr2_169031293_C_Gchr2:169031293-0.166-0.431-0.412—   
chr2_169031294_A_Gchr2:169031294-0.137-0.360-0.412—   
chr2_169031333_G_Tchr2:169031333-0.230-0.327-0.294—   
chr2_169031291_C_Gchr2:169031291-0.177-0.381-0.406—   
chr2_169031325_A_Tchr2:169031325-0.229-0.299-0.324—   
chr2_169031317_A_Tchr2:169031317-0.228-0.315-0.329—   
chr2_169031288_T_Gchr2:169031288-0.139-0.273-0.397—   
chr2_169031306_C_Tchr2:169031306-0.220-0.355-0.315—   
chr2_169031331_C_Achr2:169031331-0.199-0.264-0.382—   
chr2_169031309_C_Tchr2:169031309-0.214-0.321-0.276—   
chr2_169031226_T_Cchr2:169031226-0.213-0.272-0.212—   
chr2_169031226_T_Achr2:169031226-0.211-0.297-0.182—   
chr2_169031329_C_Achr2:169031329-0.211-0.264-0.226—   
chr2_169031225_C_Tchr2:169031225-0.210-0.305-0.182—   
chr2_169031341_T_Achr2:1690313410.2100.1450.235—   
chr2_169031324_T_Cchr2:1690313240.2020.2970.135—   
chr2_169031198_T_Gchr2:169031198-0.195-0.218-0.153—   
chr2_169031290_T_Gchr2:1690312900.1930.2460.200—   
chr2_169031291_C_Achr2:169031291-0.153-0.350-0.341—   
chr2_169031336_C_Tchr2:169031336-0.191-0.237-0.303—   
chr2_169031343_C_Achr2:169031343-0.186-0.192-0.250—   
chr2_169031322_T_Achr2:1690313220.1840.2230.188—   
chr2_169031184_A_Cchr2:1690311840.1830.1750.265—   
chr2_169031270_C_Tchr2:169031270-0.183-0.239-0.129—   
chr2_169031292_A_Tchr2:169031292-0.178-0.332-0.324—   
chr2_169031289_T_Cchr2:169031289-0.107-0.284-0.321—   
chr2_169031342_T_Achr2:1690313420.1810.2110.206—   
chr2_169031304_A_Cchr2:169031304-0.180-0.250-0.253—   
chr2_169031320_A_Cchr2:169031320-0.170-0.299-0.315—   
chr2_169031294_A_Cchr2:169031294-0.125-0.348-0.312—   
chr2_169031321_T_Achr2:169031321-0.168-0.330-0.303—   
chr2_169031260_A_Tchr2:1690312600.1680.1370.141—   
chr2_169031296_C_Gchr2:169031296-0.110-0.193-0.294—   
chr2_169031313_T_Achr2:169031313-0.146-0.228-0.291—   
chr2_169031314_T_Achr2:169031314-0.056-0.279-0.291—   
chr2_169031309_C_Achr2:169031309-0.162-0.299-0.194—   
chr2_169031289_T_Gchr2:169031289-0.133-0.317-0.285—   
chr2_169031225_C_Gchr2:169031225-0.158-0.223-0.038—   
chr2_169031323_C_Achr2:169031323-0.146-0.249-0.279—   
chr2_169031339_A_Gchr2:1690313390.1570.1900.194—   
chr2_169031290_T_Achr2:1690312900.1530.1680.182—   
chr2_169031293_C_Achr2:169031293-0.136-0.292-0.271—   
chr2_169031327_A_Tchr2:169031327-0.137-0.150-0.271—   
chr2_169031176_T_Achr2:1690311760.1510.1320.103—   
chr2_169031267_C_Gchr2:1690312670.1510.2180.259—   
chr2_169031178_A_Cchr2:1690311780.1500.1680.121—   
chr2_169031226_T_Gchr2:169031226-0.150-0.168-0.141—   
chr2_169031295_A_Cchr2:169031295-0.123-0.254-0.265—   
chr2_169031327_A_Gchr2:169031327-0.150-0.151-0.221—   
chr2_169031329_C_Gchr2:169031329-0.150-0.185-0.179—   
chr2_169031332_T_Achr2:169031332-0.125-0.272-0.265—   
chr2_169031310_G_Achr2:169031310-0.149-0.231-0.176—   
chr2_169031278_A_Gchr2:1690312780.1450.1750.212—   
chr2_169031324_T_Gchr2:1690313240.1410.2510.229—   
chr2_169031279_G_Cchr2:169031279-0.140-0.155-0.185—   
chr2_169031292_A_Cchr2:169031292-0.140-0.310-0.241—   
chr2_169031197_T_Cchr2:169031197-0.136-0.0610.091—   
chr2_169031305_A_Tchr2:169031305-0.136-0.206-0.229—   
chr2_169031308_T_Achr2:1690313080.1230.1600.241—   
chr2_169031264_A_Cchr2:169031264-0.136-0.152-0.024—   
chr2_169031316_C_Achr2:1690313160.1330.0280.076—   
chr2_169031332_T_Gchr2:169031332-0.126-0.236-0.235—   
chr2_169031311_G_Achr2:169031311-0.131-0.140-0.165—   
chr2_169031306_C_Achr2:169031306-0.131-0.236-0.165—   
chr2_169031222_T_Gchr2:169031222-0.118-0.259-0.229—   
chr2_169031316_C_Tchr2:169031316-0.076-0.256-0.229—   
chr2_169031335_A_Cchr2:1690313350.1270.2080.194—   
chr2_169031171_A_Cchr2:1690311710.1260.1020.115—   
chr2_169031315_T_Achr2:1690313150.1260.1700.118—   
chr2_169031337_A_Cchr2:1690313370.1260.1650.065—   
chr2_169031179_A_Cchr2:1690311790.1250.0630.079—   
chr2_169031335_A_Tchr2:169031335-0.125-0.190-0.200—   
chr2_169031188_G_Tchr2:169031188-0.111-0.124-0.218—   
chr2_169031313_T_Gchr2:169031313-0.087-0.178-0.218—   
chr2_169031318_T_Cchr2:169031318-0.123-0.218-0.124—   
chr2_169031311_G_Cchr2:169031311-0.122-0.174-0.176—   
chr2_169031307_C_Tchr2:169031307-0.101-0.175-0.215—   
chr2_169031295_A_Gchr2:169031295-0.034-0.162-0.212—   
chr2_169031339_A_Cchr2:1690313390.1200.1800.053—   
chr2_169031326_A_Gchr2:1690313260.1190.1550.106—   
chr2_169031326_A_Cchr2:1690313260.1170.1570.153—   
chr2_169031260_A_Cchr2:1690312600.1160.0940.124—   
chr2_169031227_G_Cchr2:169031227-0.115-0.129-0.118—   
chr2_169031266_T_Cchr2:169031266-0.115-0.178-0.100—   
chr2_169008089_G_Tchr2:169008089-0.1140.0410.115—   
chr2_169031287_G_Tchr2:169031287-0.035-0.109-0.200—   
chr2_169031317_A_Cchr2:169031317-0.112-0.223-0.159—   
chr2_169031172_A_Cchr2:1690311720.1110.0940.112—   
chr2_169031241_G_Tchr2:1690312410.1110.1120.150—   
chr2_169031276_A_Tchr2:169031276-0.111-0.1850.041—   
chr2_169008129_G_Cchr2:1690081290.058-0.046-0.196—   
chr2_169031258_T_Cchr2:169031258-0.110-0.0910.006—   
chr2_169031263_G_Cchr2:1690312630.0920.1420.194—   
chr2_169031302_C_Tchr2:169031302-0.109-0.122-0.141—   
chr2_169031304_A_Tchr2:169031304-0.107-0.169-0.141—   
chr2_169031323_C_Tchr2:169031323-0.107-0.147-0.138—   
chr2_169031194_G_Tchr2:1690311940.1060.1090.041—   
chr2_169031307_C_Gchr2:169031307-0.069-0.084-0.188—   
chr2_169031232_T_Gchr2:169031232-0.085-0.107-0.185—   
chr2_169031337_A_Tchr2:1690313370.1040.1270.082—   
chr2_169031299_T_Cchr2:169031299-0.101-0.162-0.182—   
chr2_169031330_A_Gchr2:1690313300.1030.1420.076—   
chr2_169031247_G_Tchr2:1690312470.1010.1190.050—   
chr2_169031301_T_Cchr2:1690313010.1010.1750.147—   
chr2_169031307_C_Achr2:169031307-0.097-0.155-0.179—   
chr2_169031245_A_Cchr2:1690312450.1000.1190.091—   
chr2_169031267_C_Achr2:1690312670.1000.0840.124—   
chr2_169031333_G_Cchr2:169031333-0.077-0.124-0.176—   
chr2_169008119_T_Achr2:1690081190.0990.063-0.006—   
chr2_169031311_G_Tchr2:169031311-0.099-0.110-0.144—   
chr2_169031216_G_Tchr2:1690312160.0980.1140.109—   
chr2_169031298_T_Cchr2:169031298-0.097-0.140-0.059—   
chr2_169031194_G_Achr2:1690311940.0970.102-0.003—   
chr2_169031231_A_Cchr2:169031231-0.097-0.086-0.041—   
chr2_169031259_A_Gchr2:169031259-0.097-0.142-0.079—   
chr2_169031280_T_Achr2:169031280-0.033-0.119-0.171—   
chr2_169031284_A_Gchr2:169031284-0.085-0.102-0.171—   
chr2_169031330_A_Cchr2:1690313300.0960.2110.171—   
chr2_169031186_G_Cchr2:1690311860.0950.0710.065—   
chr2_169031298_T_Achr2:169031298-0.095-0.162-0.112—   
chr2_169031325_A_Gchr2:1690313250.0940.1470.112—   
chr2_169031227_G_Tchr2:169031227-0.093-0.071-0.100—   
chr2_169031235_G_Tchr2:1690312350.0930.1040.094—   
chr2_169031241_G_Cchr2:1690312410.0930.1520.138—   
chr2_169031252_A_Cchr2:169031252-0.093-0.145-0.082—   
chr2_169031263_G_Tchr2:1690312630.0870.1570.165—   
chr2_169031278_A_Cchr2:169031278-0.093-0.119-0.018—   
chr2_169031173_G_Achr2:1690311730.0920.1290.006—   
chr2_169031227_G_Achr2:169031227-0.092-0.094-0.079—   
chr2_169031244_G_Achr2:1690312440.0920.0890.082—   
chr2_169031244_G_Cchr2:1690312440.0920.1070.118—   
chr2_169031176_T_Gchr2:1690311760.0900.0840.094—   
chr2_169031180_A_Tchr2:169031180-0.090-0.114-0.082—   
chr2_169031287_G_Achr2:1690312870.0900.1950.159—   
chr2_169031293_C_Tchr2:169031293-0.043-0.109-0.159—   
chr2_169008140_T_Gchr2:169008140-0.0880.005-0.004—   
chr2_169031239_T_Cchr2:1690312390.0880.1240.062—   
chr2_169031299_T_Gchr2:1690312990.0880.0230.071—   
chr2_169008089_G_Achr2:169008089-0.0870.0180.047—   
chr2_169031318_T_Gchr2:169031318-0.086-0.137-0.124—   
chr2_169031174_A_Cchr2:1690311740.0850.0530.094—   
chr2_169031251_G_Tchr2:169031251-0.072-0.114-0.150—   
chr2_169031283_A_Tchr2:169031283-0.085-0.122-0.135—   
chr2_169008120_C_Tchr2:1690081200.0840.015-0.078—   
chr2_169008090_A_Tchr2:169008090-0.0830.0100.082—   
chr2_169031177_T_Gchr2:1690311770.0830.0690.097—   
chr2_169031200_G_Tchr2:1690312000.0830.066-0.032—   
chr2_169031220_C_Achr2:169031220-0.083-0.165-0.018—   
chr2_169031220_C_Tchr2:1690312200.0380.0100.147—   
chr2_169031236_A_Cchr2:1690312360.0120.0460.147—   
chr2_169031304_A_Gchr2:1690313040.0830.1930.109—   
chr2_169031167_A_Cchr2:1690311670.0820.0430.100—   
chr2_169031173_G_Cchr2:1690311730.0820.0610.041—   
chr2_169031278_A_Tchr2:169031278-0.082-0.081-0.053—   
chr2_169031320_A_Gchr2:169031320-0.047-0.122-0.144—   
chr2_169031303_C_Tchr2:1690313030.0810.1220.088—   

Showing 200 of 200 in this window. Scores are the p99-scaled [−1, 1] value; click a column to sort.