Incidental Mutation 'R0322:Npc1l1'
ID 25625
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 038532-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.098) question?
Stock # R0322 (G1)
Quality Score 225
Status Validated
Chromosome 11
Chromosomal Location 6161013-6180143 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 6179042 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Leucine at position 123 (I123L)
Ref Sequence ENSEMBL: ENSMUSP00000004505 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000004505]
AlphaFold no structure available at present
Predicted Effect probably benign
Transcript: ENSMUST00000004505
AA Change: I123L

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: I123L

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 0.0898 question?
Coding Region Coverage
  • 1x: 98.7%
  • 3x: 97.5%
  • 10x: 93.8%
  • 20x: 84.3%
Validation Efficiency 98% (58/59)
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: 55 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
9130401M01Rik A T 15: 57,888,768 (GRCm39) S275T possibly damaging Het
Adam34 G T 8: 44,104,958 (GRCm39) T229N probably benign Het
Adgrb3 C A 1: 25,260,829 (GRCm39) probably benign Het
Ankhd1 T A 18: 36,791,061 (GRCm39) Y2478* probably null Het
Arl9 A G 5: 77,155,037 (GRCm39) probably benign Het
Bub1b G A 2: 118,470,099 (GRCm39) probably benign Het
Chl1 A T 6: 103,678,844 (GRCm39) probably benign Het
Cobl T A 11: 12,217,072 (GRCm39) E465V probably damaging Het
Cobll1 A T 2: 64,932,442 (GRCm39) M520K possibly damaging Het
Dll3 A G 7: 27,995,793 (GRCm39) V336A possibly damaging Het
Dnmbp T C 19: 43,843,285 (GRCm39) H1193R probably damaging Het
Fbxo43 T C 15: 36,152,338 (GRCm39) probably benign Het
Gart G A 16: 91,419,925 (GRCm39) probably benign Het
Gjc3 A T 5: 137,955,760 (GRCm39) M175K possibly damaging Het
Gpc5 T A 14: 115,636,563 (GRCm39) N415K probably benign Het
Idh2 C T 7: 79,748,005 (GRCm39) A232T probably damaging Het
Il7r A T 15: 9,510,301 (GRCm39) F251I probably benign Het
Insc A G 7: 114,391,500 (GRCm39) E141G probably damaging Het
Itm2c C T 1: 85,834,751 (GRCm39) T160M probably damaging Het
Mboat1 T C 13: 30,416,063 (GRCm39) probably benign Het
Mdm2 G T 10: 117,538,109 (GRCm39) H96Q possibly damaging Het
Mettl13 A G 1: 162,371,745 (GRCm39) probably benign Het
Mfsd4b3-ps T C 10: 39,823,526 (GRCm39) N245D probably damaging Het
Mroh2a C T 1: 88,158,402 (GRCm39) R150* probably null Het
Mtmr3 T C 11: 4,437,505 (GRCm39) Y982C possibly damaging Het
Mymk A T 2: 26,957,418 (GRCm39) L66Q probably damaging Het
Myo18a T C 11: 77,720,626 (GRCm39) S767P probably damaging Het
Ndufa8 T C 2: 35,926,634 (GRCm39) D134G probably benign Het
Noxa1 A G 2: 24,982,566 (GRCm39) F83S probably damaging Het
Ogdhl A G 14: 32,059,534 (GRCm39) T394A probably benign Het
Or4s2b T C 2: 88,509,011 (GRCm39) S264P probably damaging Het
Or5ae1 A G 7: 84,565,521 (GRCm39) Y178C probably damaging Het
Pcdh20 T C 14: 88,706,383 (GRCm39) T306A probably benign Het
Pcid2 G A 8: 13,140,775 (GRCm39) probably benign Het
Phyhip G A 14: 70,700,836 (GRCm39) V108M possibly damaging Het
Pnpla5 G T 15: 84,004,920 (GRCm39) L144M probably damaging Het
Psmb4 A G 3: 94,793,402 (GRCm39) Y160H probably benign Het
Riox2 A T 16: 59,309,752 (GRCm39) K369* probably null Het
Rnf26rt T C 6: 76,473,401 (GRCm39) Y405C probably benign Het
Sh3tc1 G A 5: 35,863,905 (GRCm39) P761S possibly damaging Het
Slc6a3 T A 13: 73,709,045 (GRCm39) V323D possibly damaging Het
Smg7 A G 1: 152,725,624 (GRCm39) probably null Het
Srrt G A 5: 137,294,870 (GRCm39) R370C probably damaging Het
Stc1 T C 14: 69,266,858 (GRCm39) V7A probably benign Het
Svep1 G T 4: 58,057,996 (GRCm39) probably benign Het
Tbpl2 A G 2: 23,984,991 (GRCm39) V51A probably benign Het
Tecr A G 8: 84,298,872 (GRCm39) Y248H probably damaging Het
Tenm3 A G 8: 48,689,947 (GRCm39) probably benign Het
Tia1 C T 6: 86,397,369 (GRCm39) A114V probably damaging Het
Tmprss11f A T 5: 86,739,275 (GRCm39) M2K probably benign Het
Tnfsf8 T C 4: 63,752,403 (GRCm39) T221A probably damaging Het
Tubgcp5 G A 7: 55,464,726 (GRCm39) G536S probably damaging Het
Tyr A T 7: 87,142,125 (GRCm39) I145N probably benign Het
Ubr4 T A 4: 139,149,729 (GRCm39) V1809E probably damaging Het
Vmn2r65 A T 7: 84,595,756 (GRCm39) N309K 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
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
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'- ATTGCAGAGGGCAGAGCCATACAC -3'
(R):5'- TTGGCACCCTAAGCATAGCACG -3'

Sequencing Primer
(F):5'- ATGCTGCCCACAGCCAG -3'
(R):5'- TGTGCCAACCAGCCTTAG -3'
Posted On 2013-04-16