Ask about this productRelated genes to: ABCB4 antibody
- Gene:
- ABCB4 NIH gene
- Name:
- ATP binding cassette subfamily B member 4
- Previous symbol:
- PGY3, MDR3
- Synonyms:
- MDR2, PFIC-3, GBD1
- Chromosome:
- 7q21.12
- Locus Type:
- gene with protein product
- Date approved:
- 1988-05-11
- Date modifiied:
- 2016-10-05
Related products to: ABCB4 antibody
Related articles to: ABCB4 antibody
- Cholestasis is a common pathological feature in multiple liver diseases which is characterized by toxic bile acid accumulation and liver injury. Emerging evidence indicated that total saikosaponins (TSS) from Radix Bupleuri (RB) could disrupt autophagic flux, probably exacerbating cholestatic liver injuries and warranting further investigation. - Source: PubMed
Publication date: 2026/05/14
Fan GuifangChen XiaoLi YufeiCai YajieYang YangHan JunsongHan QiSun RongLiu Runping - Intrahepatic Cholestasis of Pregnancy (ICP) is the most common pregnancy-related liver disorder. ABCB4 heterozygous variants are implicated in ICP, but interpretation of rare variants remains challenging, leading to many variants of uncertain significance. This study compares predictions from multiple in silico tools on nine heterozygous missense variants identified in women with ICP. Using the Genomics England Research Environment, 253 women with ICP and whole-genome sequencing data were analysed. Variants with minor allele frequency < 0.05 were filtered, and nine rare missense variants were assessed using SIFT, PolyPhen, CADD, Vasor (ABCB4-specific), and AlphaMissense. Only 44% (4/9) of variants had consistent classification across all tools. Published functional studies often conflicted with predictions. For example, T175A showed no detectable effect in HepG2/HEK293 cells but was classified as likely pathogenic by Vasor and benign by AlphaMissense. Similarly, N510S impacted protein stability functionally and was deemed likely pathogenic by Vasor but benign by AlphaMissense. In silico tools show conflicting predictions for ABCB4 rare variants, highlighting the difficulty of classification without functional or segregation data as well as the heavy reliance on computational predictions. - Source: PubMed
Publication date: 2026/05/02
Bracanovic AlexanderWilliamson CatherineZöllner JuliaDixon Peter H - Progressive familial intrahepatic cholestasis (PFIC) is a rare hereditary liver disorder that is caused by defective hepatobiliary transport. Variants in ATP binding cassette 4 ( ), encoding phosphatidylcholine floppase MDR3, are a frequent cause; however, many remain classified as variants of uncertain significance (VUS), limiting molecular diagnosis. Here, we functionally characterized a previously reported homozygous missense variant (c.431G>A, p.(Arg144Gln)) without experimental evidence of pathogenicity. An analysis using the ABCB4-specific prediction tool Vasor indicated a high probability of pathogenicity (0.88). Structural modeling suggested that Arg144Gln disrupted key electrostatic interactions essential for MDR3 membrane anchoring. Immunofluorescence analyses demonstrated markedly reduced membrane localization with residual cytoplasmic retention, consistent with complete loss of protein function. In conclusion, the p.(Arg144Gln) variant causes functional inactivation of MDR3 and represents a novel pathogenic mutation. Combined genetic, structural, and functional analyses are valuable tools for characterizing variants of uncertain significance in -associated cholestatic liver disease. - Source: PubMed
Publication date: 2026/04/02
Heinrich SophiaBehrendt AnnikaSgodda MalteGohlke HolgerAuber BerndStalke AmelieHartleben BjörnWedemeyer HeinerCantz TobiasTaubert Richard - Progressive familial intrahepatic cholestasis type 3 (PFIC3) is caused by impaired activity of ABCB4 that transports phosphatidylcholines (PC) from hepatocytes into bile. Abcb4-knockout (KO) mice have been generated, but hydrophilic muricholic acids in their bile acid (BA) pool may limit pathology and thereby hamper translation to human PFIC3. Therefore, we addressed whether Abcb4 knockdown (Abcb4-KD) in the livers of Cyp2c70-KO mice with a human-like BA composition leads to liver pathology that more closely resembles human PFIC3. - Source: PubMed
Publication date: 2026/04/08
Ke LixinMulder Niels LHovingh Milaine VHavinga RickWeersing Ellende Vries Hilde Dde Bruyn KrisztinaUstyantsev KirillBerezikov EugeneBloks Vincent WAttema BrechtWorthmann AnnaHeeren JoergWolters Justina CTiessen-Thomas RachelVerkade Henkjan JKuipers Folkertde Boer Jan Freark - Drug-induced liver injury can occur when the canalicular phospholipid floppase multidrug resistance protein 3 (Mdr2 in rodents) is inhibited, but there is still a lack of early biomarkers to detect this risk. In this study, bile duct-cannulated rats were dosed with multidrug resistance protein 3/Mdr2 inhibitor itraconazole (ITZ; 100 mg/kg/d for 3 days) to assess phospholipid changes via an untargeted-to-targeted lipidomics workflow. Untargeted profiling of bile and liver samples identified 1347 and 2475 tentative lipids, of which 221 and 404 were phosphatidylcholines (PCs) in bile and the liver, respectively. Unsupervised principal component analysis revealed strong treatment effects on bile PCs. A volcano plot indicated a selective, but not global, reduction in biliary PCs after ITZ treatment. Among these, PC 38:4 stood out as the most consistently decreased bile species. Structural elucidation using multistage collision-induced dissociation/mass spectrometry fragmentations confirmed its identity as arachidonyl PC 18:0/20:4. Subsequent absolute quantitation showed that bile PC 38:4 remained stable in controls (10.5 ± 1.02 μM; 5.6% CV) but declined rapidly after the first dose of ITZ (6.89 ± 1.50 μM at 0-4 hours) and continued to decrease to 4.22 ± 0.958 μM by day 3, a 2.7-fold decrease. Conversely, hepatic PC 38:4 showed a modest, yet significant increase (∼1.2-fold). Plasma bile acids remained unaffected, supporting a mechanism involving Mdr2 rather than the bile salt export pump. These findings identify PC 38:4 (18:0/20:4) as a sensitive and mechanistically relevant marker of Mdr2 inhibition. Monitoring PC 38:4 in nonclinical species may enable early, transporter-specific drug-induced liver injury risk assessment during drug development. SIGNIFICANCE STATEMENT: Untargeted-to-targeted lipidomics workflows identified phosphatidylcholine 38:4 as a sensitive, specific, and mechanistically linked biomarker of Mdr2 inhibition in rats. Multistage collision-induced dissociation/mass spectrometry fragmentation further confirmed the identity as arachidonyl phosphatidylcholine 18:0/20:4. Its rapid and specific decline in the presence of the Mdr2 inhibitor itraconazole offers a potential new tool for early detection of human multidrug resistance protein 3-related liver injury risk during drug development. - Source: PubMed
Publication date: 2026/02/24
Liu RenmengRabow ZacharyYang TingyuanYan XinHu YidingXiong ChenlingLai Yurong