Incidental Mutation 'P0014:Abcb4'
ID7620
Institutional Source Beutler Lab
Gene Symbol Abcb4
Ensembl Gene ENSMUSG00000042476
Gene NameATP-binding cassette, sub-family B (MDR/TAP), member 4
SynonymsPgy-2, Mdr2, Pgy2, mdr-2
MMRRC Submission 038267-MU
Accession Numbers

Ncbi RefSeq: NM_008830; MGI: 97569

Is this an essential gene? Non essential (E-score: 0.000) question?
Stock #P0014 (G1)
Quality Score
Status Validated
Chromosome5
Chromosomal Location8893717-8959231 bp(+) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) A to G at 8950083 bp
ZygosityHeterozygous
Amino Acid Change Tyrosine to Cysteine at position 1017 (Y1017C)
Ref Sequence ENSEMBL: ENSMUSP00000003717 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000003717]
Predicted Effect probably benign
Transcript: ENSMUST00000003717
AA Change: Y1017C

PolyPhen 2 Score 0.009 (Sensitivity: 0.96; Specificity: 0.77)
SMART Domains Protein: ENSMUSP00000003717
Gene: ENSMUSG00000042476
AA Change: Y1017C

DomainStartEndE-ValueType
Pfam:ABC_membrane 54 342 2e-94 PFAM
AAA 418 610 3.97e-20 SMART
Pfam:ABC_membrane 708 982 6.3e-77 PFAM
AAA 1058 1246 4.49e-19 SMART
Meta Mutation Damage Score 0.1917 question?
Coding Region Coverage
  • 1x: 85.4%
  • 3x: 80.7%
  • 10x: 66.7%
  • 20x: 50.4%
Validation Efficiency 95% (100/105)
MGI Phenotype Strain: 1857236
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] 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]
PHENOTYPE: Mice homozygous for targeted mutations that inactivate the gene are unable to secrete phospholipids into bile, leading to progressive hepatic disease, with an end stage of 3 months. [provided by MGI curators]
Allele List at MGI

All alleles(3) : Targeted(3)

Other mutations in this stock
Total: 19 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
3632451O06Rik C T 14: 49,751,659 E618K probably damaging Het
Acly T C 11: 100,484,604 I787V probably benign Het
Aldob T C 4: 49,538,153 Q325R probably benign Het
Capns2 A G 8: 92,902,214 T244A probably damaging Het
Clec16a C T 16: 10,560,156 probably benign Het
Creb3 A G 4: 43,563,265 T121A possibly damaging Het
Ddah1 A G 3: 145,853,158 D160G probably benign Het
Dhx57 A T 17: 80,275,191 H328Q probably benign Het
Dmxl2 A C 9: 54,401,764 L1901R probably damaging Het
Dnah5 T A 15: 28,403,473 L3448Q probably damaging Het
Gcdh A G 8: 84,888,525 probably null Het
Lrrc8c T C 5: 105,607,244 V295A probably benign Het
Nek1 A T 8: 61,071,747 probably benign Het
Pkp2 C T 16: 16,240,522 P356L probably benign Het
Sipa1l3 T C 7: 29,383,215 T752A probably damaging Het
Slc38a2 C A 15: 96,690,161 W494L probably damaging Het
Ttn T C 2: 76,798,470 D12734G probably damaging Het
Uggt2 A G 14: 119,044,538 S742P probably damaging Het
Vwa3b C T 1: 37,173,914 probably benign Het
Other mutations in Abcb4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00570:Abcb4 APN 5 8950073 missense probably benign 0.02
IGL00663:Abcb4 APN 5 8927916 missense probably damaging 1.00
IGL00671:Abcb4 APN 5 8930745 nonsense probably null
IGL00822:Abcb4 APN 5 8950046 missense probably benign
IGL01080:Abcb4 APN 5 8934258 missense probably damaging 1.00
IGL01152:Abcb4 APN 5 8950678 missense probably benign 0.19
IGL01329:Abcb4 APN 5 8894166 critical splice donor site probably null
IGL01483:Abcb4 APN 5 8927871 missense probably damaging 0.99
IGL01594:Abcb4 APN 5 8946071 unclassified probably null
IGL01785:Abcb4 APN 5 8915058 nonsense probably null
IGL01968:Abcb4 APN 5 8927913 missense probably benign 0.33
IGL02579:Abcb4 APN 5 8955537 missense probably damaging 1.00
IGL02654:Abcb4 APN 5 8927826 missense possibly damaging 0.80
IGL02658:Abcb4 APN 5 8934240 missense probably benign
IGL03229:Abcb4 APN 5 8940936 missense probably damaging 0.97
IGL03335:Abcb4 APN 5 8935258 missense probably benign 0.00
FR4737:Abcb4 UTSW 5 8896597 small deletion probably benign
R0102:Abcb4 UTSW 5 8909194 missense probably damaging 0.99
R0102:Abcb4 UTSW 5 8909194 missense probably damaging 0.99
R0309:Abcb4 UTSW 5 8939835 missense probably damaging 1.00
R0311:Abcb4 UTSW 5 8934243 missense probably benign
R0420:Abcb4 UTSW 5 8941050 missense probably benign 0.03
R0449:Abcb4 UTSW 5 8939885 nonsense probably null
R0609:Abcb4 UTSW 5 8947376 missense probably damaging 0.96
R1459:Abcb4 UTSW 5 8918662 missense possibly damaging 0.61
R1470:Abcb4 UTSW 5 8940968 missense probably damaging 0.98
R1470:Abcb4 UTSW 5 8940968 missense probably damaging 0.98
R1812:Abcb4 UTSW 5 8928578 critical splice donor site probably null
R1944:Abcb4 UTSW 5 8930796 missense probably damaging 1.00
R2002:Abcb4 UTSW 5 8905989 missense probably benign 0.01
R2256:Abcb4 UTSW 5 8958431 missense probably damaging 1.00
R3116:Abcb4 UTSW 5 8896610 missense possibly damaging 0.86
R4112:Abcb4 UTSW 5 8936783 critical splice acceptor site probably null
R4354:Abcb4 UTSW 5 8918771 missense probably benign 0.44
R4512:Abcb4 UTSW 5 8928573 missense probably damaging 1.00
R4588:Abcb4 UTSW 5 8947328 missense probably benign 0.01
R4628:Abcb4 UTSW 5 8907399 missense probably benign 0.08
R4708:Abcb4 UTSW 5 8915125 missense possibly damaging 0.90
R4714:Abcb4 UTSW 5 8930906 splice site probably null
R4754:Abcb4 UTSW 5 8910717 missense probably damaging 1.00
R4846:Abcb4 UTSW 5 8935180 missense probably benign
R4896:Abcb4 UTSW 5 8907267 missense possibly damaging 0.81
R4944:Abcb4 UTSW 5 8934327 critical splice donor site probably null
R4994:Abcb4 UTSW 5 8928524 missense probably damaging 1.00
R5022:Abcb4 UTSW 5 8909054 intron probably null
R5537:Abcb4 UTSW 5 8955485 missense probably damaging 0.98
R5754:Abcb4 UTSW 5 8934320 missense probably benign
R5833:Abcb4 UTSW 5 8958314 missense probably damaging 1.00
R5934:Abcb4 UTSW 5 8930806 missense probably benign 0.18
R6006:Abcb4 UTSW 5 8946026 missense probably damaging 0.99
R6146:Abcb4 UTSW 5 8896587 missense probably benign 0.05
R6183:Abcb4 UTSW 5 8918718 missense probably benign
R6260:Abcb4 UTSW 5 8934219 nonsense probably null
R6561:Abcb4 UTSW 5 8927825 missense probably benign 0.14
R7016:Abcb4 UTSW 5 8936843 missense probably benign 0.35
R7081:Abcb4 UTSW 5 8934263 missense probably benign
R7326:Abcb4 UTSW 5 8934226 missense probably benign 0.00
R7375:Abcb4 UTSW 5 8918671 missense probably benign
R7787:Abcb4 UTSW 5 8909220 missense probably damaging 1.00
R7836:Abcb4 UTSW 5 8934203 missense probably benign
R7919:Abcb4 UTSW 5 8934203 missense probably benign
RF015:Abcb4 UTSW 5 8896594 frame shift probably null
RF047:Abcb4 UTSW 5 8896595 frame shift probably null
Z1176:Abcb4 UTSW 5 8959005 missense probably damaging 1.00
Z1177:Abcb4 UTSW 5 8939906 nonsense probably null
Protein Function and Prediction

ATP-binding cassette, subfamily B, member 4 [Abcb4; alternatively P-glycoprotein 3 (PGY3) or Multidrug resistance 3 (MDR3)] is a member of the ATP-binding cassette transporter protein family.  Abcb4 facilitates the translocation of phosphatidylcholine to the inner leaflet of the membrane (1).

Background

Condition

OMIM #

Characteristics/Symptoms

Refs

Cholestasis, familial intrahepatic, of pregnancy

147480

A liver disorder characterized by pruritus and raised serum bile acid levels

(2;3)

Cholestasis, progressive familial intrahepatic 3

602347

Hepatosplenomegaly, elevated serum liver enzymes, increased gamma-glutamyltransferase activity, and a high serum bile acid concentration

(3-5)

 

Gallbladder disease 1

600803

Gallstones composed of cholesterol (cholelithiasis) are the common manifestations

(6)

 

Abcb4tm1Bor/tm1Bor; MGI:1857236

either: (involves: 129P2/OlaHsd) or (involves: 129P2/OlaHsd * FVB/N)

In this genetic background, this mouse exhibits reduced female fertility as well as bile duct inflammation, hepatic necrosis, dilated bile ducts, cholestasis, liver hemorrhage and abnormal bile secretion (7;8).  This model had increased circulating bilirubin, alanine transaminase, and aspartate transaminase levels (8).  Also, beginning at 4 to 6 months, mice develop hepatocellular carcinoma with necrosis, hemorrhage, and strong cytonuclear polymorphism unlike in wild-type mice (7).

 

Abcb4tm1Bor/tm1Bor; MGI:1857236

FVB.129P2-Abcb4tm1Bor/J

In this genetic background, homozygous animals also exhibit abnormal bile composition as well as fecal acidic sterol levels are decreased 30% compared to in wild-type mice however, fecal neutral sterol levels are normal (9). This model also had increased circulating bilirubin, alanine transaminase, and aspartate transaminase levels (9).

 

Abcb4tm1Bor/tm1Bor; MGI:1857236

involves: 129P2/OlaHsd * FVB

In this genetic background, this model also had increased circulating bilirubin, alanine transaminase, and aspartate transaminase levels (10).  Furthermore, homozygous animals had abnormal lipid homeostasis, decreased intestinal cholesterol absorption, and decreased circulating cholesterol levels (10).

References
Posted On2012-10-05
Science WriterAnne Murray