ABCB4 (ATP binding cassette subfamily B member 4)

Gene

• Entrez ID: 5244
• Gene name: ATP binding cassette subfamily B member 4
• Gene symbol: ABCB4
• Synonyms: ABC21, GBD1, ICP3, MDR2, MDR2/3, MDR3, PFIC-3, PGY3
• Chromosome: 7
• Chromosome location: 7q21.12
• Summary: The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance as well as antigen presentation. This gene encodes a full transporter and member of the p-glycoprotein family of membrane proteins with phosphatidylcholine as its substrate. The function of this protein has not yet been determined; however, it may involve transport of phospholipids from liver hepatocytes into bile. Alternative splicing of this gene results in several products of undetermined function. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs2230029	T>G	Uncertain-significance, conflicting-interpretations-of-pathogenicity, likely-benign	Non coding transcript variant, coding sequence variant, genic downstream transcript variant, synonymous variant
rs8187802	C>G,T	Likely-benign, conflicting-interpretations-of-pathogenicity, benign	Non coding transcript variant, coding sequence variant, synonymous variant
rs8187808	A>G	Conflicting-interpretations-of-pathogenicity	Genic downstream transcript variant, non coding transcript variant, coding sequence variant, synonymous variant
rs45575636	C>G,T	Uncertain-significance, conflicting-interpretations-of-pathogenicity, not-provided	Non coding transcript variant, missense variant, coding sequence variant
rs58238559	T>C	Pathogenic, benign, benign-likely-benign	Non coding transcript variant, missense variant, coding sequence variant, 5 prime UTR variant
rs61730509	C>T	Uncertain-significance, likely-pathogenic, benign	Genic downstream transcript variant, missense variant, intron variant, coding sequence variant
rs72552778	G>A	Uncertain-significance, pathogenic, pathogenic-likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs72552780	G>A,C	Pathogenic	Non coding transcript variant, upstream transcript variant, missense variant, stop gained, genic upstream transcript variant, coding sequence variant
rs121918440	G>A	Pathogenic, likely-pathogenic	Genic downstream transcript variant, intron variant, coding sequence variant, stop gained
rs121918441	G>T	Uncertain-significance, pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs121918442	G>A,T	Uncertain-significance, pathogenic	Non coding transcript variant, genic downstream transcript variant, missense variant, coding sequence variant
rs121918443	A>G	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs138773456	G>A	Uncertain-significance, pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs141677867	G>A	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs143456575	A>C,G	Likely-pathogenic, uncertain-significance	Synonymous variant, intron variant, coding sequence variant, missense variant, non coding transcript variant
rs199504845	A>C,G	Pathogenic, uncertain-significance	Synonymous variant, coding sequence variant, non coding transcript variant, stop gained
rs201498350	A>G	Pathogenic	Genic downstream transcript variant, intron variant
rs371394487	G>A	Conflicting-interpretations-of-pathogenicity	Synonymous variant, non coding transcript variant, genic downstream transcript variant, coding sequence variant
rs375315619	T>C	Conflicting-interpretations-of-pathogenicity, pathogenic, likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs376926391	G>A,T	Pathogenic	Coding sequence variant, synonymous variant, genic upstream transcript variant, non coding transcript variant, stop gained
rs377160065	G>A	Likely-pathogenic, pathogenic	5 prime UTR variant, non coding transcript variant, coding sequence variant, stop gained
rs387906526	TATATAG>-	Pathogenic	Frameshift variant, coding sequence variant, genic upstream transcript variant, non coding transcript variant, upstream transcript variant
rs387906527	A>-	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs387906528	CT>TTG	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs387906529	->C	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs397514620	G>A,C	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs533310204	G>A,T	Likely-pathogenic	Stop gained, genic downstream transcript variant, coding sequence variant, non coding transcript variant, synonymous variant
rs571555115	G>A	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs748842753	G>A,C	Pathogenic	Stop gained, non coding transcript variant, coding sequence variant, genic downstream transcript variant, missense variant
rs750829010	C>G	Pathogenic	Splice donor variant, genic downstream transcript variant
rs752563752	C>T	Likely-pathogenic	Splice acceptor variant
rs752916287	C>G,T	Uncertain-significance, pathogenic	Intron variant, coding sequence variant, genic downstream transcript variant, missense variant
rs753104429	A>-,AA	Pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant
rs754287486	G>A	Likely-pathogenic	5 prime UTR variant, coding sequence variant, non coding transcript variant, missense variant
rs754565782	G>A	Likely-pathogenic, uncertain-significance	Coding sequence variant, non coding transcript variant, genic downstream transcript variant, missense variant
rs757693457	C>T	Likely-pathogenic	Non coding transcript variant, coding sequence variant, 5 prime UTR variant, missense variant
rs759202962	G>A	Likely-pathogenic, pathogenic	Non coding transcript variant, coding sequence variant, genic downstream transcript variant, stop gained
rs760153272	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs764513998	C>G,T	Likely-pathogenic, pathogenic	Splice donor variant, genic downstream transcript variant
rs771437431	C>A,G	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, genic downstream transcript variant, non coding transcript variant, synonymous variant
rs772823352	C>A	Pathogenic	Splice acceptor variant
rs794727183	C>T	Pathogenic	Splice donor variant
rs863225298	G>C	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs863225299	C>T	Uncertain-significance, likely-pathogenic	Upstream transcript variant, coding sequence variant, non coding transcript variant, genic upstream transcript variant, missense variant
rs886042562	G>A	Pathogenic	Stop gained, intron variant, genic downstream transcript variant, coding sequence variant
rs886043725	T>A	Pathogenic	Stop gained, genic downstream transcript variant, coding sequence variant, non coding transcript variant
rs886043734	TC>AT	Pathogenic	Stop gained, genic downstream transcript variant, coding sequence variant, non coding transcript variant
rs1037196284	C>A,T	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1051861187	A>G	Likely-pathogenic	Non coding transcript variant, genic downstream transcript variant, coding sequence variant, missense variant
rs1187517509	T>A	Likely-pathogenic	Non coding transcript variant, coding sequence variant, genic downstream transcript variant, missense variant
rs1245472904	C>A,T	Pathogenic	Splice donor variant, genic downstream transcript variant
rs1326932143	T>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs1348606984	T>C,G	Pathogenic	Splice acceptor variant
rs1458423947	G>A	Pathogenic	Non coding transcript variant, stop gained, coding sequence variant
rs1471180323	T>G	Likely-benign, conflicting-interpretations-of-pathogenicity	Intron variant
rs1554401324	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, downstream transcript variant, genic downstream transcript variant, stop gained
rs1554401344	T>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1554407511	C>A	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs1554417376	TTTT>-,TTTTT	Pathogenic	Genic upstream transcript variant, coding sequence variant, non coding transcript variant, frameshift variant
rs1562945221	->T	Pathogenic, likely-pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant, genic downstream transcript variant
rs1562949296	C>G	Pathogenic	Splice acceptor variant, missense variant, genic downstream transcript variant, coding sequence variant
rs1562961442	C>T	Pathogenic	Intron variant, splice donor variant
rs1562963055	ACACTGG>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1562965036	C>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1562965098	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs1562965250	T>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1562975541	TGCGAACCAGGGCA>CCTGAATGG	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1562976061	A>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1562976167	C>A	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs1562983272	G>T	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs1562983531	T>C	Pathogenic	Splice acceptor variant
rs1562988165	->A	Pathogenic	Coding sequence variant, non coding transcript variant, intron variant, frameshift variant
rs1562989885	T>C	Pathogenic	Splice acceptor variant, genic upstream transcript variant, upstream transcript variant
rs1563009379	T>A	Pathogenic	Coding sequence variant, genic upstream transcript variant, non coding transcript variant, stop gained
rs1563012148	T>C	Likely-pathogenic	Coding sequence variant, genic upstream transcript variant, non coding transcript variant, missense variant
rs1584665400	G>A	Likely-pathogenic	Genic downstream transcript variant, stop gained, coding sequence variant, non coding transcript variant
rs1584671714	->A	Likely-pathogenic	Genic downstream transcript variant, frameshift variant, coding sequence variant, non coding transcript variant
rs1584678508	T>-	Pathogenic	Genic downstream transcript variant, frameshift variant, coding sequence variant, non coding transcript variant
rs1584684209	AT>-	Likely-pathogenic	Frameshift variant, intron variant, coding sequence variant, genic downstream transcript variant
rs1584742063	T>G	Likely-pathogenic	Splice acceptor variant
rs1584747270	A>C	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1584750653	C>T	Likely-pathogenic	Intron variant
rs1584750660	C>A	Likely-pathogenic	Splice donor variant
rs1584754706	C>A,T	Likely-pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1584754766	T>-	Likely-pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant
rs1584763429	G>-	Likely-pathogenic	5 prime UTR variant, frameshift variant, coding sequence variant, non coding transcript variant

Transcription factors

Transcription factor	Regulation	Reference
NR1H4	Activation	14527955

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	19674157
GO:0005524	Function	ATP binding	IEA
GO:0005548	Function	Phospholipid transporter activity	TAS
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IDA	24045840
GO:0005829	Component	Cytosol	IDA
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0005886	Component	Plasma membrane	IDA	24045840, 24806754
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	TAS	7912658
GO:0005925	Component	Focal adhesion	IDA
GO:0006629	Process	Lipid metabolic process	TAS	7912658
GO:0015629	Component	Actin cytoskeleton	IDA
GO:0016020	Component	Membrane	TAS	7912658
GO:0016021	Component	Integral component of membrane	IBA	21873635
GO:0016324	Component	Apical plasma membrane	IDA	8898203, 19674157
GO:0016887	Function	ATPase activity	IEA
GO:0019216	Process	Regulation of lipid metabolic process	TAS
GO:0030136	Component	Clathrin-coated vesicle	IEA
GO:0032376	Process	Positive regulation of cholesterol transport	IDA	17523162
GO:0032376	Process	Positive regulation of cholesterol transport	IMP	24045840
GO:0032782	Process	Bile acid secretion	ISS
GO:0042626	Function	ATPase-coupled transmembrane transporter activity	IBA	21873635
GO:0042626	Function	ATPase-coupled transmembrane transporter activity	IDA	17523162
GO:0042626	Function	ATPase-coupled transmembrane transporter activity	IMP	8898203
GO:0042910	Function	Xenobiotic transmembrane transporter activity	IBA	21873635
GO:0045121	Component	Membrane raft	IEA
GO:0045332	Process	Phospholipid translocation	IBA	21873635
GO:0045332	Process	Phospholipid translocation	IDA	8898203
GO:0045332	Process	Phospholipid translocation	IMP	24806754
GO:0046581	Component	Intercellular canaliculus	IEA
GO:0055085	Process	Transmembrane transport	TAS
GO:0055088	Process	Lipid homeostasis	IDA	17523162
GO:0061092	Process	Positive regulation of phospholipid translocation	IDA	17523162
GO:0070062	Component	Extracellular exosome	HDA	23533145
GO:0090554	Function	Phosphatidylcholine floppase activity	IBA	21873635
GO:0090554	Function	Phosphatidylcholine floppase activity	IDA	8898203, 17523162
GO:0090554	Function	Phosphatidylcholine floppase activity	IMP	24045840, 24806754
GO:0090555	Function	Phosphatidylethanolamine flippase activity	IBA	21873635
GO:0099038	Function	Ceramide floppase activity	IDA	8898203
GO:0099040	Process	Ceramide translocation	IDA	8898203
GO:1901557	Process	Response to fenofibrate	ISS
GO:1903413	Process	Cellular response to bile acid	IDA	17523162
GO:2001140	Process	Positive regulation of phospholipid transport	IDA	8898203
GO:2001140	Process	Positive regulation of phospholipid transport	IMP	24045840

Other IDs

• MIM: 171060
• HGNC: 45
• e!Ensembl: ENSG00000005471

Protein

• UniProt ID: P21439
• Protein name: Phosphatidylcholine translocator ABCB4 (EC 7.6.2.1) (ATP-binding cassette sub-family B member 4) (Multidrug resistance protein 3) (P-glycoprotein 3)
• Protein function: Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion. Functions as a floppase that translocates specifically phosphatidylcholine (PC) from the inner to the outer leaflet of the canalicular membrane bilayer into the canaliculi of hepatocytes. Translocation of PC makes the biliary phospholipids available for extraction into the canaliculi lumen by bile salt mixed micelles and therefore protects the biliary tree from the detergent activity of bile salts (PubMed:7957936, PubMed:8898203, PubMed:9366571, PubMed:17523162, PubMed:23468132, PubMed:24806754, PubMed:24723470, PubMed:24594635, PubMed:21820390). Plays a role in the recruitment of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) molecules to nonraft membranes and to further enrichment of SM and cholesterol in raft membranes in hepatocytes (PubMed:23468132). Required for proper phospholipid bile formation (By similarity). Indirectly involved in cholesterol efflux activity from hepatocytes into the canalicular lumen in the presence of bile salts in an ATP-dependent manner (PubMed:24045840). Promotes biliary phospholipid secretion as canaliculi-containing vesicles from the canalicular plasma membrane (PubMed:9366571, PubMed:28012258). In cooperation with ATP8B1, functions to protect hepatocytes from the deleterious detergent activity of bile salts (PubMed:21820390). Does not confer multidrug resistance (By similarity).
• PDB: 6S7P
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00664	ABC_membrane	57 → 345	ABC transporter transmembrane region	Family
  PF00005	ABC_tran	412 → 561	ABC transporter	Domain
  PF00664	ABC_membrane	711 → 985	ABC transporter transmembrane region	Family
  PF00005	ABC_tran	1052 → 1210	ABC transporter	Domain

• Sequence:

  MDLEAAKNGTAWRPTSAEGDFELGISSKQKRKKTKTVKMIGVLTLFRYSDWQDKLFMSLG
  TIMAIAHGSGLPLMMIVFGEMTDKFVDTAGNFSFPVNFSLSLLNPGKILEEEMTRYAYYY
  SGLGAGVLVAAYIQVSFWTLAAGRQIRKIRQKFFHAILRQEIGWFDINDTTELNTRLTDD
  ISKISEGIGDKVGMFFQAVATFFAGFIVGFIRGWKLTLVIMAISPILGLSAAVWAKILSA
  FSDKELAAYAKAGAVAEEALGAIRTVIAFGGQNKELERYQKHLENAKEIGIKKAISANIS
  MGIAFLLIYASYALAFWYGSTLVISKEYTIGNAMTVFFSILIGAFSVGQAAPCIDAFANA
  RGAAYVIFDIIDNNPKIDSFSERGHKPDSIKGNLEFNDVHFSYPSRANVKILKGLNLKVQ
  SGQTVALVGSSGCGKSTTVQLIQRLYDPDEGTINIDGQDIRNFNVNYLREIIGVVSQEPV
  LFSTTIAENICYGRGNVTMDEIKKAVKEANAYEFIMKLPQKFDTLVGERGAQLSGGQKQR
  IAIARALVRNPKILLLDEATSALDTESEAEVQAALDKAREGRTTIVIAHRLSTVRNADVI
  AGFEDGVIVEQGSHSELMKKEGVYFKLVNMQTSGSQIQSEEFELNDEKAATRMAPNGWKS
  RLFRHSTQKNLKNSQMCQKSLDVETDGLEANVPPVSFLKVLKLNKTEWPYFVVGTVCAIA
  NGGLQPAFSVIFSEIIAIFGPGDDAVKQQKCNIFSLIFLFLGIISFFTFFLQGFTFGKAG
  EILTRRLRSMAFKAMLRQDMSWFDDHKNSTGALSTRLATDAAQVQGATGTRLALIAQNIA
  NLGTGIIISFIYGWQLTLLLLAVVPIIAVSGIVEMKLLAGNAKRDKKELEAAGKIATEAI
  ENIRTVVSLTQERKFESMYVEKLYGPYRNSVQKAHIYGITFSISQAFMYFSYAGCFRFGA
  YLIVNGHMRFRDVILVFSAIVFGAVALGHASSFAPDYAKAKLSAAHLFMLFERQPLIDSY
  SEEGLKPDKFEGNITFNEVVFNYPTRANVPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQ
  LLERFYDPLAGTVFVDFGFQLLDGQEAKKLNVQWLRAQLGIVSQEPILFDCSIAENIAYG
  DNSRVVSQDEIVSAAKAANIHPFIETLPHKYETRVGDKGTQLSGGQKQRIAIARALIRQP
  QILLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEH
  GTHQQLLAQKGIYFSMVSVQAGTQNL

• Sequence length: 1286