Incidental Mutation 'R1944:Npc1l1'
ID 216480
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 039962-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.098) question?
Stock # R1944 (G1)
Quality Score 225
Status Not validated
Chromosome 11
Chromosomal Location 6161013-6180143 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 6164588 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Phenylalanine at position 1154 (I1154F)
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: I1154F

PolyPhen 2 Score 0.670 (Sensitivity: 0.86; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: I1154F

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: 99.1%
  • 3x: 98.4%
  • 10x: 96.7%
  • 20x: 93.9%
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: 102 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcb4 A T 5: 8,980,796 (GRCm39) N593Y probably damaging Het
Adamts16 C T 13: 70,940,005 (GRCm39) S406N possibly damaging Het
Adgrg1 G A 8: 95,733,928 (GRCm39) V350I probably damaging Het
Adgrv1 A T 13: 81,659,030 (GRCm39) D2051E probably damaging Het
Adrb2 C A 18: 62,312,484 (GRCm39) V114L probably damaging Het
Ago3 A G 4: 126,247,520 (GRCm39) V599A probably damaging Het
AI837181 T C 19: 5,476,257 (GRCm39) V140A probably damaging Het
Ankrd16 T A 2: 11,788,443 (GRCm39) probably null Het
Arnt2 A G 7: 83,992,959 (GRCm39) S194P probably benign Het
Art2b T C 7: 101,229,153 (GRCm39) N249D probably benign Het
Atat1 A G 17: 36,220,232 (GRCm39) L60P probably damaging Het
Atp2b1 A T 10: 98,858,793 (GRCm39) I1159F probably damaging Het
Atrip T A 9: 108,900,935 (GRCm39) I135F probably damaging Het
Bbs4 T G 9: 59,237,698 (GRCm39) probably null Het
Bdp1 A T 13: 100,210,889 (GRCm39) probably null Het
Best2 A G 8: 85,737,390 (GRCm39) probably null Het
Cacna1c A G 6: 118,583,227 (GRCm39) I1516T probably damaging Het
Cadps2 T C 6: 23,599,479 (GRCm39) I276V probably damaging Het
Carmil3 T C 14: 55,736,087 (GRCm39) S610P probably damaging Het
Caskin1 A G 17: 24,719,745 (GRCm39) I375V probably damaging Het
Ccdc168 G A 1: 44,101,009 (GRCm39) P30S probably damaging Het
Ccdc92b A G 11: 74,520,835 (GRCm39) I46V probably benign Het
Clec11a G T 7: 43,954,098 (GRCm39) T285K probably benign Het
Clk3 G T 9: 57,672,469 (GRCm39) T111K probably benign Het
Col6a6 G A 9: 105,586,583 (GRCm39) R1813C probably damaging Het
Col7a1 G A 9: 108,789,078 (GRCm39) V798I unknown Het
Ctrb1 C A 8: 112,416,151 (GRCm39) W45L probably damaging Het
Cubn T A 2: 13,283,349 (GRCm39) S3530C probably benign Het
Dio1 A G 4: 107,163,977 (GRCm39) probably null Het
Dock5 A T 14: 67,994,584 (GRCm39) Y1825* probably null Het
Duox1 A T 2: 122,177,001 (GRCm39) Q1476L probably damaging Het
Dync2h1 A T 9: 7,001,377 (GRCm39) H3877Q probably damaging Het
Enkd1 A G 8: 106,434,208 (GRCm39) S85P probably damaging Het
Erap1 A G 13: 74,794,758 (GRCm39) D139G probably benign Het
Ern1 A G 11: 106,312,776 (GRCm39) S202P probably damaging Het
F11r T C 1: 171,289,459 (GRCm39) Y261H probably damaging Het
Glp2r A T 11: 67,637,618 (GRCm39) S138T probably benign Het
Gpt2 A G 8: 86,244,625 (GRCm39) Y306C probably damaging Het
Grid2 G C 6: 63,886,045 (GRCm39) R147P probably damaging Het
Gtdc1 A G 2: 44,642,198 (GRCm39) F128L possibly damaging Het
H2-T15 A G 17: 36,368,897 (GRCm39) F61S probably damaging Het
Hacd4 T C 4: 88,341,303 (GRCm39) T154A possibly damaging Het
Heatr6 G T 11: 83,660,046 (GRCm39) L530F probably damaging Het
Hoxd8 A T 2: 74,537,056 (GRCm39) D256V probably damaging Het
Ints6 T C 14: 62,931,089 (GRCm39) N865D probably benign Het
Itpkc G T 7: 26,927,084 (GRCm39) P277T possibly damaging Het
Klc4 T C 17: 46,947,553 (GRCm39) N383S probably damaging Het
Klra6 T C 6: 129,995,908 (GRCm39) Y150C possibly damaging Het
Krt32 T A 11: 99,975,670 (GRCm39) probably null Het
Krt33a T C 11: 99,903,535 (GRCm39) N199S probably benign Het
Krt39 A C 11: 99,410,649 (GRCm39) D174E probably damaging Het
Krt82 G A 15: 101,456,970 (GRCm39) R137W probably damaging Het
Lgmn A T 12: 102,368,183 (GRCm39) S193T probably damaging Het
Limch1 G A 5: 67,156,442 (GRCm39) R300H probably damaging Het
Lrpap1 T A 5: 35,254,974 (GRCm39) I221F probably benign Het
Lsmem1 GTACATACATACATACATACATACATACA GTACATACATACATACATACATACATACATACA 12: 40,235,260 (GRCm39) probably null Het
Macf1 T C 4: 123,264,459 (GRCm39) D4883G probably damaging Het
Man2b2 A G 5: 36,973,524 (GRCm39) V485A probably benign Het
Map3k19 T C 1: 127,750,859 (GRCm39) T831A probably benign Het
Mdfic2 A G 6: 98,225,151 (GRCm39) I44T probably benign Het
Megf6 C G 4: 154,340,523 (GRCm39) D471E possibly damaging Het
Mettl8 A T 2: 70,803,623 (GRCm39) F268L probably damaging Het
Miip T C 4: 147,950,422 (GRCm39) E58G probably benign Het
Mycbp2 T A 14: 103,466,840 (GRCm39) S1308C probably damaging Het
Myo15a T C 11: 60,392,909 (GRCm39) F2194L probably damaging Het
Nav3 T C 10: 109,552,391 (GRCm39) N1817S probably damaging Het
Ndel1 A T 11: 68,720,746 (GRCm39) H313Q probably benign Het
Neb A T 2: 52,118,862 (GRCm39) H3931Q probably benign Het
Nfkb2 T A 19: 46,296,491 (GRCm39) V253E probably damaging Het
Niban1 T C 1: 151,571,979 (GRCm39) I308T probably damaging Het
Nono T C X: 100,485,429 (GRCm39) probably null Het
Nr2e1 T C 10: 42,448,774 (GRCm39) T155A probably benign Het
Oosp2 C T 19: 11,626,959 (GRCm39) probably null Het
Or2b2 A T 13: 21,887,287 (GRCm39) I39F possibly damaging Het
Pdap1 G A 5: 145,069,726 (GRCm39) T93I probably benign Het
Pde6c T A 19: 38,145,967 (GRCm39) D418E probably damaging Het
Pdha1 T A X: 158,910,354 (GRCm39) D255V probably damaging Het
Polr2h T A 16: 20,537,796 (GRCm39) D64E probably benign Het
Psmb3 T C 11: 97,601,981 (GRCm39) F117S probably benign Het
Ptprq A T 10: 107,418,249 (GRCm39) M1709K probably benign Het
Rbm15 C T 3: 107,238,868 (GRCm39) R510H probably damaging Het
Rgs7 A T 1: 174,980,769 (GRCm39) M85K possibly damaging Het
Rpl27-ps3 T A 18: 6,332,669 (GRCm39) V13D probably damaging Het
Rtp2 T A 16: 23,746,316 (GRCm39) D105V possibly damaging Het
Scd3 T C 19: 44,224,219 (GRCm39) Y151H probably benign Het
Slc30a6 T G 17: 74,715,858 (GRCm39) V106G probably damaging Het
Slco1a4 T C 6: 141,785,276 (GRCm39) I105V probably benign Het
Sun3 T C 11: 8,988,296 (GRCm39) I9V probably benign Het
Syne2 T C 12: 76,121,318 (GRCm39) V5928A probably damaging Het
Tbr1 T A 2: 61,642,600 (GRCm39) S622T probably damaging Het
Tgm3 A G 2: 129,871,889 (GRCm39) N306D probably damaging Het
Tmem132d A G 5: 127,860,828 (GRCm39) *1098Q probably null Het
Tmem140 T C 6: 34,849,747 (GRCm39) Y88H probably damaging Het
Trim60 A T 8: 65,453,964 (GRCm39) V95E possibly damaging Het
Vamp3 A G 4: 151,140,617 (GRCm39) probably null Het
Vmn1r235 A C 17: 21,481,785 (GRCm39) T37P probably damaging Het
Vmn2r81 T G 10: 79,129,571 (GRCm39) L821V probably damaging Het
Vmn2r97 A G 17: 19,160,500 (GRCm39) D545G probably benign Het
Vps13c A T 9: 67,793,558 (GRCm39) D437V probably damaging Het
Wtip A T 7: 33,818,363 (GRCm39) M268K probably benign Het
Zfhx2 G T 14: 55,312,189 (GRCm39) F168L probably benign Het
Zscan22 G A 7: 12,637,767 (GRCm39) R53K probably damaging 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
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'- CCTACAGGCAAGAGAAATGAACTTC -3'
(R):5'- ACACCCTGATCTTTGGCAGG -3'

Sequencing Primer
(F):5'- GCAAGAGAAATGAACTTCAGGAAAC -3'
(R):5'- AGGATCTCCAATGTGTTCTACCAG -3'
Posted On 2014-08-01