Incidental Mutation 'R1455:Npc1l1'
ID 161739
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 039510-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.098) question?
Stock # R1455 (G1)
Quality Score 225
Status Not validated
Chromosome 11
Chromosomal Location 6161013-6180143 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 6178174 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Glutamic Acid at position 412 (V412E)
Ref Sequence ENSEMBL: ENSMUSP00000004505 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000004505]
AlphaFold no structure available at present
Predicted Effect possibly damaging
Transcript: ENSMUST00000004505
AA Change: V412E

PolyPhen 2 Score 0.656 (Sensitivity: 0.87; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: V412E

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
Coding Region Coverage
  • 1x: 98.9%
  • 3x: 97.9%
  • 10x: 94.8%
  • 20x: 87.9%
Validation Efficiency
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: 41 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4921509C19Rik T C 2: 151,314,824 (GRCm39) N285D possibly damaging Het
Adam9 T G 8: 25,483,125 (GRCm39) M227L probably benign Het
Ankrd35 A G 3: 96,585,471 (GRCm39) D21G probably damaging Het
Arhgap32 C T 9: 32,171,381 (GRCm39) A1387V probably benign Het
Atg4d T A 9: 21,182,097 (GRCm39) V306E probably damaging Het
Brsk1 G A 7: 4,707,250 (GRCm39) V268M probably damaging Het
Cfap300 T G 9: 8,022,457 (GRCm39) N255T probably benign Het
Clec4a4 A G 6: 122,989,758 (GRCm39) E133G possibly damaging Het
Col24a1 T A 3: 145,166,593 (GRCm39) L1076H probably damaging Het
Ddah1 G T 3: 145,594,864 (GRCm39) R208L probably benign Het
Dysf A G 6: 84,090,368 (GRCm39) N960S probably benign Het
Egln2 A G 7: 26,859,796 (GRCm39) Y306H probably damaging Het
Fgfr1 T C 8: 26,052,292 (GRCm39) V293A possibly damaging Het
Gja3 A G 14: 57,273,842 (GRCm39) Y177H probably damaging Het
Glul T A 1: 153,782,845 (GRCm39) probably null Het
Gprc5a G A 6: 135,056,245 (GRCm39) V231I probably benign Het
Kdm4d C A 9: 14,375,691 (GRCm39) A56S probably damaging Het
Lingo4 G A 3: 94,306,699 (GRCm39) probably benign Het
Map6 A G 7: 98,917,421 (GRCm39) T65A probably damaging Het
Mmrn2 T C 14: 34,121,089 (GRCm39) I653T probably benign Het
Ndufa12 A G 10: 94,039,176 (GRCm39) T70A probably benign Het
Nfe2l3 C A 6: 51,434,744 (GRCm39) P435T possibly damaging Het
Or51a39 A T 7: 102,363,205 (GRCm39) Y138* probably null Het
Or6aa1 A T 7: 86,043,803 (GRCm39) F301Y probably damaging Het
Pcnx1 T C 12: 82,020,008 (GRCm39) F1344L probably damaging Het
Pi4ka A G 16: 17,181,818 (GRCm39) V297A probably benign Het
Pole2 G A 12: 69,254,703 (GRCm39) L381F probably benign Het
Pramel7 T C 2: 87,320,067 (GRCm39) T409A probably benign Het
Proc C G 18: 32,256,451 (GRCm39) M405I probably damaging Het
Serinc2 C A 4: 130,158,133 (GRCm39) A105S probably damaging Het
Slc4a10 G T 2: 62,117,274 (GRCm39) K744N probably damaging Het
Spdye4c A T 2: 128,438,478 (GRCm39) I279F probably damaging Het
Srcap G T 7: 127,129,822 (GRCm39) R568L probably damaging Het
Stag3 T A 5: 138,309,997 (GRCm39) M1215K probably benign Het
Tenm3 C T 8: 48,732,083 (GRCm39) A1274T possibly damaging Het
Tet2 A G 3: 133,179,406 (GRCm39) V1253A possibly damaging Het
Tns2 C T 15: 102,017,369 (GRCm39) R281C probably damaging Het
Trip12 T C 1: 84,736,821 (GRCm39) I800V probably benign Het
Zfc3h1 T C 10: 115,248,013 (GRCm39) I1072T probably benign Het
Zfp148 T A 16: 33,315,835 (GRCm39) probably null Het
Zfp941 A G 7: 140,392,687 (GRCm39) V224A probably benign 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
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
R4807:Npc1l1 UTSW 11 6,168,723 (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'- GAAATGGTCCTTCCAGTCCACCAG -3'
(R):5'- CGTAAGCGCAGATTCTCACCTCAC -3'

Sequencing Primer
(F):5'- TTGACACAGCAGTCAGTGAG -3'
(R):5'- TCTTCGAGAGCTGGGGAAC -3'
Posted On 2014-03-14