Incidental Mutation 'R0352:Npc1l1'
ID 29717
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 038558-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.098) question?
Stock # R0352 (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 6173076 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Methionine to Valine at position 788 (M788V)
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: M788V

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
SMART Domains Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: M788V

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 0.0715 question?
Coding Region Coverage
  • 1x: 99.0%
  • 3x: 97.9%
  • 10x: 95.4%
  • 20x: 90.0%
Validation Efficiency 100% (70/70)
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: 67 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2700049A03Rik C T 12: 71,184,804 (GRCm39) T64M possibly damaging Het
3110040N11Rik G T 7: 81,438,208 (GRCm39) N49K probably benign Het
Adrb1 T A 19: 56,711,293 (GRCm39) F164I probably damaging Het
Aplf C T 6: 87,630,866 (GRCm39) V190I probably benign Het
Aqr A G 2: 114,000,533 (GRCm39) Y50H probably damaging Het
Arfgef3 A C 10: 18,537,135 (GRCm39) I182R probably benign Het
Cacna1b G A 2: 24,515,244 (GRCm39) probably benign Het
Casp9 A G 4: 141,532,841 (GRCm39) T246A probably damaging Het
Clcn6 A G 4: 148,099,063 (GRCm39) S427P probably damaging Het
Cnga1 T C 5: 72,761,846 (GRCm39) N556S possibly damaging Het
Cntnap2 G A 6: 45,969,018 (GRCm39) probably null Het
Col11a2 T G 17: 34,261,501 (GRCm39) V120G probably benign Het
Cux2 A C 5: 122,022,802 (GRCm39) probably benign Het
Dmrt2 T C 19: 25,656,026 (GRCm39) S542P probably damaging Het
Dnah7b A G 1: 46,316,286 (GRCm39) H3133R probably damaging Het
Drosha G A 15: 12,837,374 (GRCm39) R286Q unknown Het
Eipr1 A G 12: 28,816,784 (GRCm39) D47G probably damaging Het
Fras1 T G 5: 96,874,399 (GRCm39) Y2275D probably damaging Het
Grm4 C T 17: 27,670,865 (GRCm39) probably benign Het
Hebp1 A G 6: 135,129,918 (GRCm39) V100A possibly damaging Het
Hivep2 G A 10: 14,019,039 (GRCm39) V1937I possibly damaging Het
Hs3st6 T C 17: 24,977,168 (GRCm39) V216A probably damaging Het
Hsd17b4 T C 18: 50,324,851 (GRCm39) I688T probably benign Het
Hydin T C 8: 111,296,533 (GRCm39) probably null Het
Iws1 A G 18: 32,217,258 (GRCm39) E426G probably damaging Het
Klrb1f T C 6: 129,030,680 (GRCm39) S64P probably damaging Het
Lacc1 C T 14: 77,272,629 (GRCm39) G56R probably damaging Het
Lcmt2 A G 2: 120,969,377 (GRCm39) S569P probably benign Het
Lipm C T 19: 34,090,275 (GRCm39) probably benign Het
Lum A G 10: 97,404,471 (GRCm39) H122R probably damaging Het
Magi2 A G 5: 20,270,664 (GRCm39) Y15C probably damaging Het
Mal A T 2: 127,482,286 (GRCm39) I39N probably damaging Het
Mgme1 A G 2: 144,118,319 (GRCm39) H197R probably benign Het
Mmrn1 A T 6: 60,921,955 (GRCm39) K137N probably benign Het
Myh3 T A 11: 66,981,254 (GRCm39) C706S possibly damaging Het
Myo18b A T 5: 113,022,389 (GRCm39) probably benign Het
Myom1 A G 17: 71,352,744 (GRCm39) E356G possibly damaging Het
Nfib A G 4: 82,422,954 (GRCm39) probably benign Het
Or9a2 C T 6: 41,749,058 (GRCm39) M58I probably damaging Het
Pdha2 A G 3: 140,917,457 (GRCm39) V17A probably benign Het
Pgap1 A T 1: 54,525,617 (GRCm39) probably benign Het
Polr1a G T 6: 71,897,747 (GRCm39) probably benign Het
Ppp1r16a C T 15: 76,574,999 (GRCm39) probably benign Het
Pramel20 A T 4: 143,297,878 (GRCm39) probably benign Het
Pramel21 A T 4: 143,342,559 (GRCm39) D222V possibly damaging Het
Prmt2 A T 10: 76,044,337 (GRCm39) V405D possibly damaging Het
Psg26 T A 7: 18,209,181 (GRCm39) Y409F probably benign Het
Psme3ip1 A G 8: 95,314,639 (GRCm39) F73S probably damaging Het
Ptges G T 2: 30,793,144 (GRCm39) Y29* probably null Het
Ptrhd1 A G 12: 4,286,399 (GRCm39) T97A probably benign Het
Ripk3 T A 14: 56,024,200 (GRCm39) probably benign Het
Rnf114 A T 2: 167,353,136 (GRCm39) I136F probably benign Het
Serinc5 A G 13: 92,844,497 (GRCm39) probably null Het
Slc17a3 C T 13: 24,039,841 (GRCm39) S293F probably damaging Het
Slc23a2 C A 2: 131,902,716 (GRCm39) M495I probably benign Het
Slc52a3 T A 2: 151,849,433 (GRCm39) L360* probably null Het
Snapc1 C T 12: 74,021,806 (GRCm39) R81C probably damaging Het
Syt5 A G 7: 4,544,170 (GRCm39) V290A probably benign Het
Szt2 G A 4: 118,239,790 (GRCm39) A1931V unknown Het
Tasp1 A G 2: 139,793,378 (GRCm39) probably null Het
Tcp10a C A 17: 7,593,805 (GRCm39) D43E probably damaging Het
Tnfsf11 A T 14: 78,516,408 (GRCm39) Y187N probably benign Het
Tppp2 T A 14: 52,156,807 (GRCm39) N61K possibly damaging Het
Wwtr1 A T 3: 57,482,548 (GRCm39) W100R probably damaging Het
Zfp623 A G 15: 75,820,433 (GRCm39) D463G probably benign Het
Zfp990 A G 4: 145,263,174 (GRCm39) I57M probably damaging Het
Zmat5 G A 11: 4,672,413 (GRCm39) C10Y 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
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'- ATTGGTGAGCACAGAGCCCCAAAC -3'
(R):5'- TCTTTCTAGGTGAGCAAGGGCTGTC -3'

Sequencing Primer
(F):5'- AAACATTCTCTCTCAGAATACTGTCC -3'
(R):5'- AGCCCAGGCTTTCAGAAG -3'
Posted On 2013-04-24