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
- 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 - Cholestatic liver disease (CLD) is characterized by disrupted bile acid (BA) homeostasis and excessive accumulation of toxic bile acids in the liver. While both genetic and acquired factors are known to contribute to its pathogenesis, the full spectrum of underlying pathological mechanisms remains incompletely understood, and treatment options are limited. Cardiotrophin-like cytokine factor 1 (CLCF1), a CNTFR ligand, plays a pivotal role in energy metabolic homeostasis, yet its role in cholestasis remains unclear. Here, we show that hepatic CLCF1 expression is markedly upregulated in cholestatic patients and mouse models (all mice used in this study were male). Hepatocyte-specific Cntfr deletion exacerbates DDC-induced cholestasis and fibrosis, whereas AAV-mediated hepatic Clcf1 overexpression attenuates cholestatic liver injury and fibrosis in both Abcb4 knockout (Mdr2) and DDC-fed mice. Mechanistically, CLCF1 suppresses BA synthesis enzymes independently of hepatic FXR-SHP signaling, and selectively enriches FXR-agonistic BAs (e.g., LCA) in the gut, activating the intestinal FXR-FGF15 axis. Gut-restricted FXR antagonism partially reverses CLCF1-mediated hepatoprotection, underscoring the gut-liver axis as a critical effector. Furthermore, CLCF1 remodels the microbiota to favor Firmicutes, enhancing BA excretion. Altogether, our data demonstrate that CLCF1 mitigates CLD through suppressing BA synthesis and enhancing BA excretion. CLCF1 may represent a promising therapeutic avenue for cholestasis. - Source: PubMed
Publication date: 2026/03/16
Liu ManSu YingxiHu YujieShen MengBao SurigugeGong YanqingJi YinglanWang LingfeiZhang YujieWang XiaoyiYang HuiChang YongshengZhou Lu - Cholestatic liver disease can progress to advanced stages if left untreated and is lack of effective therapeutic options, highlighting the urgent need for new therapeutic targets. - Source: PubMed
Publication date: 2026/03/12
Fan GuifangLi XinLi YiranDuan ShuniQin WenqingLi YajingSun RongXie KaihongHuo ZixuanQu JiaorongLiu Runping