Incidental Mutation 'R1588:Npc1l1'
ID 177649
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 039625-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.098) question?
Stock # R1588 (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 G at 6167785 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Alanine at position 1002 (V1002A)
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: V1002A

PolyPhen 2 Score 0.012 (Sensitivity: 0.96; Specificity: 0.78)
SMART Domains Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: V1002A

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: 98.0%
  • 10x: 95.0%
  • 20x: 87.7%
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: 56 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcc4 A G 14: 118,771,484 (GRCm39) V869A probably benign Het
Ablim1 C T 19: 57,071,979 (GRCm39) M1I probably null Het
Adamts13 A T 2: 26,865,687 (GRCm39) I81F probably benign Het
Akap11 A T 14: 78,747,685 (GRCm39) N1567K possibly damaging Het
Arrdc4 G A 7: 68,391,484 (GRCm39) T261M possibly damaging Het
C4b T C 17: 34,959,999 (GRCm39) I326V probably benign Het
Casp8ap2 G A 4: 32,640,541 (GRCm39) A532T probably benign Het
Ccdc134 A G 15: 82,019,337 (GRCm39) T187A probably benign Het
Cdh8 T C 8: 99,917,039 (GRCm39) N359D probably damaging Het
Cep97 A G 16: 55,748,184 (GRCm39) L82P probably damaging Het
Cfap53 A T 18: 74,440,444 (GRCm39) R404S probably benign Het
Chrng C A 1: 87,135,229 (GRCm39) F179L probably damaging Het
Ddi1 A T 9: 6,265,391 (GRCm39) I326K probably damaging Het
Decr2 T C 17: 26,302,002 (GRCm39) T243A possibly damaging Het
Dip2c T C 13: 9,715,900 (GRCm39) V1502A probably damaging Het
Edem1 T C 6: 108,818,640 (GRCm39) V216A probably damaging Het
Fat2 A C 11: 55,174,230 (GRCm39) V2161G probably damaging Het
Fbn1 T C 2: 125,161,034 (GRCm39) T2169A probably benign Het
Fmn1 T C 2: 113,196,043 (GRCm39) V581A unknown Het
Hip1r A T 5: 124,134,638 (GRCm39) D350V probably damaging Het
Ift140 G A 17: 25,306,959 (GRCm39) R898H probably damaging Het
Il12a A G 3: 68,602,896 (GRCm39) I159V probably benign Het
Itprid1 A G 6: 55,955,488 (GRCm39) E1032G possibly damaging Het
Kl A G 5: 150,906,097 (GRCm39) E489G probably benign Het
Klhl3 T C 13: 58,161,712 (GRCm39) E461G probably damaging Het
Masp1 T C 16: 23,313,404 (GRCm39) Y177C probably damaging Het
Nop58 T A 1: 59,742,031 (GRCm39) Y187N probably damaging Het
Ntaq1 T A 15: 58,021,285 (GRCm39) probably null Het
Ntrk1 A T 3: 87,687,384 (GRCm39) Y683* probably null Het
Or11g26 A G 14: 50,753,584 (GRCm39) I308V probably benign Het
Or13j1 C T 4: 43,705,923 (GRCm39) C215Y probably damaging Het
Or2w4 C T 13: 21,796,083 (GRCm39) D19N probably benign Het
Or8k21 T C 2: 86,144,874 (GRCm39) Y252C probably damaging Het
Osbpl6 T C 2: 76,409,560 (GRCm39) V367A probably benign Het
Phip A G 9: 82,782,881 (GRCm39) W855R probably damaging Het
Phlpp1 A G 1: 106,308,115 (GRCm39) S1131G probably damaging Het
Pkdrej A T 15: 85,701,442 (GRCm39) V1498E probably benign Het
Pramel22 G T 4: 143,382,121 (GRCm39) L192M probably damaging Het
Prkaa2 T C 4: 104,908,420 (GRCm39) N152D probably damaging Het
Ptpro T A 6: 137,420,592 (GRCm39) V1007D probably damaging Het
Pxdn G A 12: 30,052,558 (GRCm39) V732M probably damaging Het
Rccd1 C T 7: 79,969,859 (GRCm39) W223* probably null Het
Riox2 T A 16: 59,295,946 (GRCm39) S16T possibly damaging Het
Scn5a C T 9: 119,350,367 (GRCm39) V836I probably damaging Het
Serpinf1 G A 11: 75,301,076 (GRCm39) R380C probably damaging Het
Sf3b1 A T 1: 55,036,336 (GRCm39) N912K probably benign Het
Shprh T A 10: 11,040,488 (GRCm39) C134S probably damaging Het
Skint8 T A 4: 111,785,924 (GRCm39) C123* probably null Het
Slc16a13 G T 11: 70,109,421 (GRCm39) S360* probably null Het
Srr A G 11: 74,799,629 (GRCm39) I282T possibly damaging Het
Trpm1 T C 7: 63,873,565 (GRCm39) F607L possibly damaging Het
Ttn T C 2: 76,539,870 (GRCm39) D34372G probably benign Het
Tub C T 7: 108,628,888 (GRCm39) T401I probably damaging Het
Wdhd1 T C 14: 47,493,693 (GRCm39) E9G probably damaging Het
Yipf3 T A 17: 46,561,787 (GRCm39) F198Y possibly damaging Het
Zfp955a C T 17: 33,460,791 (GRCm39) R447K 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
R1455:Npc1l1 UTSW 11 6,178,174 (GRCm39) missense possibly damaging 0.66
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'- AACGAGACCTTGTCCTGTCAGTCC -3'
(R):5'- TCACACTATCAGTGTCCCCTGGAG -3'

Sequencing Primer
(F):5'- TCACTGTGCCCCAGAAAGG -3'
(R):5'- CTATGGCCCTGCATATGGAG -3'
Posted On 2014-04-24