Incidental Mutation 'R5369:Npc1l1'
ID 429558
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 042946-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.098) question?
Stock # R5369 (G1)
Quality Score 225
Status Validated
Chromosome 11
Chromosomal Location 6161013-6180143 bp(-) (GRCm39)
Type of Mutation critical splice donor site (2 bp from exon)
DNA Base Change (assembly) A to G at 6167705 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000004505 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000004505]
AlphaFold no structure available at present
Predicted Effect probably null
Transcript: ENSMUST00000004505
SMART Domains Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447

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 0.9485 question?
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.7%
  • 10x: 97.4%
  • 20x: 95.6%
Validation Efficiency 99% (77/78)
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: 74 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
A2ml1 T C 6: 128,545,796 (GRCm39) T444A probably damaging Het
A330070K13Rik G A 5: 130,407,932 (GRCm39) probably benign Het
Abcb8 C T 5: 24,605,137 (GRCm39) R108C possibly damaging Het
Acbd5 T A 2: 23,002,522 (GRCm39) L508Q probably damaging Het
Asb15 T C 6: 24,562,563 (GRCm39) V175A probably benign Het
B3galnt2 T C 13: 14,169,010 (GRCm39) probably null Het
BC024139 A C 15: 76,004,422 (GRCm39) S711R probably benign Het
Bod1l A G 5: 41,984,526 (GRCm39) I508T probably damaging Het
Btnl6 T A 17: 34,726,959 (GRCm39) R524* probably null Het
C3 C A 17: 57,528,159 (GRCm39) D687Y probably benign Het
Ccbe1 G A 18: 66,194,485 (GRCm39) A367V probably benign Het
Ccr1 A T 9: 123,764,326 (GRCm39) M68K probably damaging Het
Cd27 T A 6: 125,211,327 (GRCm39) probably benign Het
Celf2 C A 2: 7,085,892 (GRCm39) probably benign Het
Cfap54 T C 10: 92,897,119 (GRCm39) probably benign Het
Cfap97 A G 8: 46,622,687 (GRCm39) K26E probably damaging Het
Clcn4 T A 7: 7,299,032 (GRCm39) I48F probably benign Het
Cnot7 A T 8: 40,947,061 (GRCm39) N238K probably benign Het
Colec12 A G 18: 9,866,750 (GRCm39) I654V unknown Het
Dip2a A G 10: 76,128,194 (GRCm39) I22T probably damaging Het
Eif4g3 C T 4: 137,910,645 (GRCm39) T1375M possibly damaging Het
Eml5 C T 12: 98,825,042 (GRCm39) G725D probably damaging Het
F12 T C 13: 55,566,304 (GRCm39) E496G probably benign Het
Fam227a A T 15: 79,499,637 (GRCm39) S573T probably benign Het
Fnip1 T C 11: 54,393,415 (GRCm39) V593A probably benign Het
Focad T A 4: 88,039,610 (GRCm39) probably benign Het
Frem1 A G 4: 82,919,976 (GRCm39) I460T possibly damaging Het
Galnt10 T G 11: 57,656,573 (GRCm39) probably null Het
Gm5592 A T 7: 40,867,635 (GRCm39) probably benign Het
Gm6185 A T 1: 161,037,330 (GRCm39) noncoding transcript Het
Gm7935 A T 15: 73,952,963 (GRCm39) noncoding transcript Het
Grb14 C T 2: 64,747,653 (GRCm39) V369I probably benign Het
Gstm5 G A 3: 107,805,782 (GRCm39) A198T probably damaging Het
Herc2 T A 7: 55,832,448 (GRCm39) V3048D probably damaging Het
Htra4 T G 8: 25,523,585 (GRCm39) I327L possibly damaging Het
Ifi209 T C 1: 173,464,873 (GRCm39) M1T probably null Het
Ints6 T C 14: 62,981,384 (GRCm39) T135A probably damaging Het
Itpr1 T A 6: 108,496,385 (GRCm39) I2604N probably damaging Het
Krt6a T A 15: 101,600,993 (GRCm39) M268L probably benign Het
Lrp1b G T 2: 40,894,625 (GRCm39) S2201* probably null Het
Lrp2 T C 2: 69,289,904 (GRCm39) N3645S probably benign Het
Lrrc15 A T 16: 30,091,722 (GRCm39) I539N possibly damaging Het
Map3k6 T C 4: 132,974,992 (GRCm39) I675T probably damaging Het
Map3k9 T A 12: 81,768,826 (GRCm39) E1074V probably damaging Het
Med13l T A 5: 118,862,075 (GRCm39) S339R probably benign Het
Mrps18a T C 17: 46,436,552 (GRCm39) probably benign Het
Mtcl2 T C 2: 156,882,654 (GRCm39) E466G probably damaging Het
Nat8f2 G T 6: 85,844,854 (GRCm39) Y169* probably null Het
Nlrp1b A G 11: 71,072,625 (GRCm39) I406T probably benign Het
Or10z1 A G 1: 174,078,007 (GRCm39) V162A probably damaging Het
Or5ac20 A T 16: 59,104,743 (GRCm39) M39K probably damaging Het
Ostf1 C T 19: 18,558,689 (GRCm39) G198E probably benign Het
Pcsk5 A G 19: 17,558,619 (GRCm39) V596A probably damaging Het
Pde4c T C 8: 71,202,754 (GRCm39) *647Q probably null Het
Pkm A T 9: 59,577,917 (GRCm39) I245F probably damaging Het
Prss3b T A 6: 41,009,940 (GRCm39) R131S probably benign Het
Ptprj T C 2: 90,299,985 (GRCm39) H179R probably benign Het
Rapgef2 A T 3: 78,976,739 (GRCm39) S1356T probably benign Het
Rbm45 T A 2: 76,200,594 (GRCm39) L41Q probably damaging Het
Rsf1 ATGGCG ATGGCGACGGTGGCG 7: 97,229,111 (GRCm39) probably benign Het
Scara5 CG C 14: 65,997,111 (GRCm39) probably null Het
Scel A T 14: 103,823,929 (GRCm39) I386F probably benign Het
Serpinb5 A T 1: 106,809,487 (GRCm39) N298Y possibly damaging Het
Sirt3 A T 7: 140,449,406 (GRCm39) L180Q probably damaging Het
Slc24a2 C T 4: 86,909,625 (GRCm39) V698I probably damaging Het
Slc43a3 A T 2: 84,788,067 (GRCm39) H483L probably damaging Het
Snrnp35 A G 5: 124,628,262 (GRCm39) D25G probably benign Het
Snrnp40 T C 4: 130,256,439 (GRCm39) S55P probably damaging Het
Snx9 T A 17: 5,970,855 (GRCm39) C399S probably damaging Het
Ttbk2 T C 2: 120,655,743 (GRCm39) probably benign Het
Vmn1r1 A G 1: 181,985,341 (GRCm39) V108A possibly damaging Het
Vmn1r201 T A 13: 22,659,672 (GRCm39) N295K probably benign Het
Zfp292 G A 4: 34,807,491 (GRCm39) P1851L possibly damaging Het
Zfp472 A T 17: 33,196,717 (GRCm39) D264V 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
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
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'- GAGGTTCTATACGCTGCTAGG -3'
(R):5'- TTGGGCACAGAATGGGAGTC -3'

Sequencing Primer
(F):5'- TATACGCTGCTAGGCCCCTG -3'
(R):5'- AGTCAGGACAGGAGCTGCC -3'
Posted On 2016-09-06