Incidental Mutation 'R4807:Npc1l1'
ID 370773
Institutional Source Beutler Lab
Gene Symbol Npc1l1
Ensembl Gene ENSMUSG00000020447
Gene Name NPC1 like intracellular cholesterol transporter 1
Synonyms Niemann-Pick disease, type C1, 9130221N23Rik
MMRRC Submission 042426-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.098) question?
Stock # R4807 (G1)
Quality Score 225
Status Validated
Chromosome 11
Chromosomal Location 6161013-6180143 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 6168723 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Cysteine at position 886 (Y886C)
Ref Sequence ENSEMBL: ENSMUSP00000004505 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000004505]
AlphaFold no structure available at present
Predicted Effect probably damaging
Transcript: ENSMUST00000004505
AA Change: Y886C

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: Y886C

DomainStartEndE-ValueType
signal peptide 1 20 N/A INTRINSIC
Pfam:NPC1_N 28 283 8.7e-74 PFAM
low complexity region 294 307 N/A INTRINSIC
transmembrane domain 348 370 N/A INTRINSIC
Pfam:Patched 385 897 4.7e-52 PFAM
Pfam:Sterol-sensing 661 815 5.7e-55 PFAM
Pfam:MMPL 665 830 2.3e-11 PFAM
Pfam:Patched 1063 1268 6.2e-34 PFAM
Meta Mutation Damage Score 0.9182 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.5%
  • 10x: 96.9%
  • 20x: 94.2%
Validation Efficiency 98% (86/88)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a multi-pass membrane protein. It contains a conserved N-terminal Niemann-Pick C1 (NPC1) domain and a putative sterol-sensing domain (SSD) which includes a YQRL motif functioning as a plasma membrane to trans-Golgi network transport signal in other proteins. This protein takes up free cholesterol into cells through vesicular endocytosis and plays a critical role in the absorption of intestinal cholesterol. It also has the ability to transport alpha-tocopherol (vitamin E). The drug ezetimibe targets this protein and inhibits the absorption of intestinal cholesterol and alpha-tocopherol. In addition, this protein may play a critical role in regulating lipid metabolism. Polymorphic variations in this gene are associated with plasma total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and coronary heart disease (CHD) risk. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
PHENOTYPE: Mice homozygous for a targeted null mutation exhibit normal intestinal development, fertility and plasma cholesterol and triglyceride levels; however, intestinal cholesterol absorption was substantially reduced. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 84 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca16 C T 7: 120,139,832 (GRCm39) A1499V probably damaging Het
Agap3 T A 5: 24,682,114 (GRCm39) D386E probably damaging Het
Ahdc1 C A 4: 132,791,624 (GRCm39) T955K possibly damaging Het
Ankrd9 A G 12: 110,943,669 (GRCm39) Y122H probably benign Het
Apc2 G T 10: 80,150,196 (GRCm39) R1721L probably benign Het
Arfgef3 A G 10: 18,522,385 (GRCm39) V547A probably benign Het
Arhgap42 T C 9: 9,046,629 (GRCm39) N203D possibly damaging Het
Arl6ip1 AAAATAAATAAATAAATAAATAAATA AAAATAAATAAATAAATAAATAAATAAATA 7: 117,721,122 (GRCm39) probably benign Het
Arsi G A 18: 61,049,723 (GRCm39) G202E probably benign Het
Aspm T A 1: 139,405,657 (GRCm39) F1515I probably damaging Het
Baz1a T C 12: 54,945,267 (GRCm39) T1363A probably benign Het
Cacng3 C T 7: 122,353,732 (GRCm39) A72V probably benign Het
Casp8ap2 T C 4: 32,644,505 (GRCm39) C1193R possibly damaging Het
Ccr3 A G 9: 123,829,334 (GRCm39) Y223C probably damaging Het
Clcn3 C A 8: 61,387,564 (GRCm39) L201F probably damaging Het
Cltc A C 11: 86,591,902 (GRCm39) probably benign Het
Cyp19a1 G T 9: 54,083,930 (GRCm39) T86K possibly damaging Het
Ddx24 A T 12: 103,385,720 (GRCm39) F248L probably damaging Het
Ddx60 G A 8: 62,432,372 (GRCm39) V885I probably damaging Het
Dync2h1 T C 9: 7,139,422 (GRCm39) I1404M probably benign Het
Emilin2 A T 17: 71,580,443 (GRCm39) V761E probably damaging Het
Endou C T 15: 97,629,113 (GRCm39) C13Y probably benign Het
Ep400 C A 5: 110,843,444 (GRCm39) probably null Het
Fbxo33 C A 12: 59,265,998 (GRCm39) D90Y probably damaging Het
Fryl A G 5: 73,198,705 (GRCm39) F2641L probably benign Het
Gbp2b A G 3: 142,304,006 (GRCm39) I34V probably benign Het
Ghdc T C 11: 100,661,051 (GRCm39) H38R probably damaging Het
Gm10722 T C 9: 3,000,937 (GRCm39) C6R probably benign Het
Gpr63 A C 4: 25,007,446 (GRCm39) M57L probably benign Het
Gprc5c A G 11: 114,755,324 (GRCm39) S3G probably damaging Het
Grk4 A T 5: 34,909,552 (GRCm39) M539L probably benign Het
Gulo C T 14: 66,227,833 (GRCm39) M366I probably benign Het
Heatr5a T C 12: 51,924,303 (GRCm39) H1970R probably damaging Het
Hmbox1 T C 14: 65,062,998 (GRCm39) probably benign Het
Ighg2b T C 12: 113,267,965 (GRCm39) probably benign Het
Il1b A T 2: 129,212,226 (GRCm39) C9S probably benign Het
Itpkb A T 1: 180,162,440 (GRCm39) probably benign Het
Kcnn1 T A 8: 71,300,822 (GRCm39) H473L probably damaging Het
Kidins220 C T 12: 25,107,284 (GRCm39) S1579L probably damaging Het
Kif1b A T 4: 149,332,378 (GRCm39) probably benign Het
Lyg2 A T 1: 37,950,148 (GRCm39) M60K possibly damaging Het
Mak16 G T 8: 31,656,161 (GRCm39) H107Q probably benign Het
Mapkap1 G A 2: 34,487,434 (GRCm39) probably null Het
Mastl A G 2: 23,022,855 (GRCm39) S623P probably benign Het
Mccc1 T C 3: 36,039,195 (GRCm39) Y46C probably damaging Het
Mdn1 T G 4: 32,685,651 (GRCm39) probably null Het
Med25 T A 7: 44,534,043 (GRCm39) T31S probably benign Het
Mprip G A 11: 59,648,846 (GRCm39) G850D probably benign Het
Mrpl10 T C 11: 96,932,449 (GRCm39) I8T probably benign Het
Msr1 T C 8: 40,095,668 (GRCm39) probably benign Het
Myo3b T A 2: 69,936,056 (GRCm39) I99N probably damaging Het
Neurod6 A T 6: 55,655,640 (GRCm39) N332K probably damaging Het
Nsmaf T C 4: 6,398,542 (GRCm39) probably null Het
Ntn4 C T 10: 93,480,362 (GRCm39) R29C probably damaging Het
Or5d47 T A 2: 87,804,095 (GRCm39) I305L probably benign Het
Plppr2 A G 9: 21,855,810 (GRCm39) N261S probably damaging Het
Prkar2a T A 9: 108,617,584 (GRCm39) probably benign Het
Pxk G A 14: 8,144,133 (GRCm38) V294M probably damaging Het
Rars1 A G 11: 35,699,973 (GRCm39) F608L possibly damaging Het
Rasa3 A G 8: 13,664,633 (GRCm39) F60L probably damaging Het
Rbm47 C T 5: 66,176,647 (GRCm39) A490T possibly damaging Het
Sardh T C 2: 27,079,539 (GRCm39) I918V probably benign Het
Saxo5 A G 8: 3,529,004 (GRCm39) K193R possibly damaging Het
Sdhc T C 1: 170,963,626 (GRCm39) Y80C probably damaging Het
Selp T A 1: 163,971,505 (GRCm39) M653K probably damaging Het
Slc6a17 T C 3: 107,407,803 (GRCm39) D56G possibly damaging Het
Slco1b2 T C 6: 141,615,195 (GRCm39) S367P probably damaging Het
Spry4 TTGAGGTCC T 18: 38,723,328 (GRCm39) probably null Het
Strip2 T A 6: 29,925,092 (GRCm39) Y143* probably null Het
Sycp2 T C 2: 178,035,754 (GRCm39) probably benign Het
Tex30 C A 1: 44,126,118 (GRCm39) V204L possibly damaging Het
Tln2 G T 9: 67,239,015 (GRCm39) T1087K probably benign Het
Tmeff2 A C 1: 51,018,546 (GRCm39) N176T probably benign Het
Togaram2 C G 17: 72,004,918 (GRCm39) T324R probably damaging Het
Trpc3 C T 3: 36,688,531 (GRCm39) R836Q probably benign Het
Trpm7 A C 2: 126,673,149 (GRCm39) L535V probably benign Het
Vmn1r213 G A 13: 23,195,775 (GRCm39) W119* probably null Het
Vps29 T G 5: 122,500,951 (GRCm39) V176G probably damaging Het
Vsig10l A G 7: 43,113,173 (GRCm39) T144A possibly damaging Het
Wdr11 T C 7: 129,229,746 (GRCm39) Y844H probably benign Het
Zbp1 A T 2: 173,053,999 (GRCm39) M174K probably damaging Het
Zfp341 G A 2: 154,487,786 (GRCm39) probably benign Het
Zfp638 G A 6: 83,920,040 (GRCm39) R546H probably damaging Het
Zfp820 A T 17: 22,042,853 (GRCm39) M1K probably null Het
Other mutations in Npc1l1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00163:Npc1l1 APN 11 6,174,199 (GRCm39) missense probably damaging 1.00
IGL01348:Npc1l1 APN 11 6,177,974 (GRCm39) missense probably damaging 1.00
IGL01891:Npc1l1 APN 11 6,164,280 (GRCm39) missense probably damaging 1.00
IGL01897:Npc1l1 APN 11 6,177,879 (GRCm39) missense probably benign
IGL02098:Npc1l1 APN 11 6,164,581 (GRCm39) missense probably damaging 0.99
IGL02121:Npc1l1 APN 11 6,178,157 (GRCm39) missense probably benign
IGL02724:Npc1l1 APN 11 6,164,684 (GRCm39) missense possibly damaging 0.88
IGL02947:Npc1l1 APN 11 6,179,246 (GRCm39) missense probably benign 0.01
IGL03328:Npc1l1 APN 11 6,168,643 (GRCm39) nonsense probably null
R0137:Npc1l1 UTSW 11 6,178,148 (GRCm39) nonsense probably null
R0322:Npc1l1 UTSW 11 6,179,042 (GRCm39) missense probably benign
R0352:Npc1l1 UTSW 11 6,173,076 (GRCm39) missense probably benign 0.00
R0492:Npc1l1 UTSW 11 6,173,040 (GRCm39) missense possibly damaging 0.82
R0918:Npc1l1 UTSW 11 6,168,239 (GRCm39) missense probably damaging 1.00
R1300:Npc1l1 UTSW 11 6,177,859 (GRCm39) missense probably damaging 1.00
R1455:Npc1l1 UTSW 11 6,178,174 (GRCm39) missense possibly damaging 0.66
R1588:Npc1l1 UTSW 11 6,167,785 (GRCm39) missense probably benign 0.01
R1803:Npc1l1 UTSW 11 6,178,846 (GRCm39) missense probably damaging 1.00
R1882:Npc1l1 UTSW 11 6,167,473 (GRCm39) splice site probably null
R1944:Npc1l1 UTSW 11 6,164,588 (GRCm39) missense possibly damaging 0.67
R1945:Npc1l1 UTSW 11 6,175,199 (GRCm39) nonsense probably null
R1945:Npc1l1 UTSW 11 6,164,588 (GRCm39) missense possibly damaging 0.67
R3155:Npc1l1 UTSW 11 6,171,840 (GRCm39) missense probably benign
R4343:Npc1l1 UTSW 11 6,167,773 (GRCm39) missense probably benign
R4504:Npc1l1 UTSW 11 6,178,741 (GRCm39) missense possibly damaging 0.61
R4610:Npc1l1 UTSW 11 6,178,215 (GRCm39) missense probably damaging 1.00
R4829:Npc1l1 UTSW 11 6,164,010 (GRCm39) critical splice donor site probably null
R5135:Npc1l1 UTSW 11 6,174,245 (GRCm39) missense possibly damaging 0.94
R5290:Npc1l1 UTSW 11 6,172,221 (GRCm39) missense probably benign 0.00
R5369:Npc1l1 UTSW 11 6,167,705 (GRCm39) critical splice donor site probably null
R5388:Npc1l1 UTSW 11 6,164,733 (GRCm39) missense probably damaging 1.00
R5532:Npc1l1 UTSW 11 6,174,245 (GRCm39) missense probably damaging 0.98
R5540:Npc1l1 UTSW 11 6,164,546 (GRCm39) missense probably damaging 1.00
R5754:Npc1l1 UTSW 11 6,177,839 (GRCm39) missense probably damaging 1.00
R5760:Npc1l1 UTSW 11 6,179,031 (GRCm39) missense probably benign 0.02
R6057:Npc1l1 UTSW 11 6,167,806 (GRCm39) missense possibly damaging 0.66
R6388:Npc1l1 UTSW 11 6,174,145 (GRCm39) missense probably damaging 1.00
R6644:Npc1l1 UTSW 11 6,164,014 (GRCm39) missense probably damaging 0.98
R6644:Npc1l1 UTSW 11 6,164,013 (GRCm39) missense probably damaging 1.00
R6756:Npc1l1 UTSW 11 6,165,153 (GRCm39) missense probably damaging 1.00
R6790:Npc1l1 UTSW 11 6,164,260 (GRCm39) splice site probably null
R7006:Npc1l1 UTSW 11 6,167,731 (GRCm39) missense probably benign
R7062:Npc1l1 UTSW 11 6,167,807 (GRCm39) missense probably benign
R7273:Npc1l1 UTSW 11 6,168,320 (GRCm39) missense probably damaging 1.00
R7383:Npc1l1 UTSW 11 6,167,777 (GRCm39) missense probably benign 0.30
R8003:Npc1l1 UTSW 11 6,165,129 (GRCm39) missense probably benign 0.01
R8081:Npc1l1 UTSW 11 6,167,768 (GRCm39) missense probably benign 0.01
R8272:Npc1l1 UTSW 11 6,179,327 (GRCm39) nonsense probably null
R8549:Npc1l1 UTSW 11 6,168,675 (GRCm39) missense probably damaging 1.00
R8849:Npc1l1 UTSW 11 6,179,038 (GRCm39) missense probably damaging 0.97
R8887:Npc1l1 UTSW 11 6,175,665 (GRCm39) missense probably damaging 1.00
R8907:Npc1l1 UTSW 11 6,178,157 (GRCm39) missense probably benign 0.28
R9102:Npc1l1 UTSW 11 6,164,684 (GRCm39) missense possibly damaging 0.88
R9289:Npc1l1 UTSW 11 6,168,355 (GRCm39) nonsense probably null
R9626:Npc1l1 UTSW 11 6,177,854 (GRCm39) missense probably benign 0.05
R9785:Npc1l1 UTSW 11 6,180,090 (GRCm39) missense unknown
X0022:Npc1l1 UTSW 11 6,178,058 (GRCm39) missense probably damaging 1.00
Z1177:Npc1l1 UTSW 11 6,175,209 (GRCm39) missense possibly damaging 0.92
Z1177:Npc1l1 UTSW 11 6,168,681 (GRCm39) missense probably damaging 0.99
Z1177:Npc1l1 UTSW 11 6,164,343 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- GCTGCAGAAACAGAGCATGC -3'
(R):5'- TATCTGAGTGCGTCCCTGAG -3'

Sequencing Primer
(F):5'- GAGACCAACCACTTACTGATTAGGG -3'
(R):5'- TGAGTCTGCCTCCGAGCATC -3'
Posted On 2016-02-04