Incidental Mutation 'R5540:Npc1l1'
ID 435901
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 043098-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.098) question?
Stock # R5540 (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 6164546 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Proline at position 1168 (S1168P)
Ref Sequence ENSEMBL: ENSMUSP00000004505 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000004505]
AlphaFold no structure available at present
Predicted Effect probably damaging
Transcript: ENSMUST00000004505
AA Change: S1168P

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: S1168P

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: 99.9%
  • 3x: 99.7%
  • 10x: 98.6%
  • 20x: 96.1%
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: 74 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700008O03Rik A G 7: 44,012,371 (GRCm39) S15P probably damaging Het
Actl7a A T 4: 56,744,388 (GRCm39) H305L probably benign Het
Adam26b C A 8: 43,974,654 (GRCm39) C116F probably damaging Het
Adgrl2 A G 3: 148,543,198 (GRCm39) probably null Het
Akr1b10 A G 6: 34,371,047 (GRCm39) T238A probably damaging Het
Akr1c18 A G 13: 4,187,178 (GRCm39) V186A probably benign Het
Alpk3 G A 7: 80,745,184 (GRCm39) V1311M probably damaging Het
Aox1 A G 1: 58,143,569 (GRCm39) N1229S probably benign Het
Apobec3 T A 15: 79,782,120 (GRCm39) N43K probably benign Het
Arid1a A C 4: 133,407,765 (GRCm39) D2247E unknown Het
Asph A G 4: 9,635,906 (GRCm39) L77S probably damaging Het
Cd300ld T A 11: 114,878,231 (GRCm39) T94S probably damaging Het
Celf2 T C 2: 6,558,743 (GRCm39) T382A probably benign Het
Cfap54 C T 10: 92,808,470 (GRCm39) A1402T possibly damaging Het
Chrnb1 A T 11: 69,686,476 (GRCm39) V48E probably benign Het
Col6a5 T A 9: 105,739,975 (GRCm39) E2548V probably benign Het
Crebrf A G 17: 26,961,071 (GRCm39) D56G possibly damaging Het
Dctn5 A G 7: 121,734,275 (GRCm39) T40A probably benign Het
Dmxl2 A T 9: 54,301,141 (GRCm39) N2323K probably benign Het
Dync1h1 A G 12: 110,627,384 (GRCm39) Q4021R probably benign Het
Dyrk1a T G 16: 94,486,202 (GRCm39) probably null Het
Ephb3 T A 16: 21,039,610 (GRCm39) F454Y probably damaging Het
Fbxo38 A G 18: 62,647,864 (GRCm39) probably null Het
Flg T C 3: 93,184,923 (GRCm39) F15S probably damaging Het
Fndc3b G A 3: 27,555,651 (GRCm39) P301L probably damaging Het
Fpr-rs7 C T 17: 20,334,356 (GRCm39) G45R probably damaging Het
Garin3 A G 11: 46,295,715 (GRCm39) N29S probably damaging Het
Gfi1 T A 5: 107,867,991 (GRCm39) T360S probably damaging Het
Grik4 T C 9: 42,432,243 (GRCm39) H918R probably damaging Het
Hpx A G 7: 105,241,119 (GRCm39) S385P possibly damaging Het
Kdm5b A G 1: 134,558,979 (GRCm39) D1501G probably damaging Het
Kif20b A T 19: 34,915,860 (GRCm39) M546L probably benign Het
Map3k9 G T 12: 81,819,587 (GRCm39) N222K probably damaging Het
Me1 A G 9: 86,561,926 (GRCm39) L53P possibly damaging Het
Mis18bp1 T C 12: 65,195,520 (GRCm39) E748G possibly damaging Het
Morc3 T A 16: 93,644,268 (GRCm39) N186K probably benign Het
Mtor A G 4: 148,539,165 (GRCm39) T221A probably benign Het
Muc6 A G 7: 141,235,850 (GRCm39) probably null Het
Myh8 C A 11: 67,177,266 (GRCm39) T444N probably benign Het
Myo7b A G 18: 32,140,143 (GRCm39) Y216H probably damaging Het
Myom1 G A 17: 71,416,782 (GRCm39) V1382M probably damaging Het
Nbeal2 A T 9: 110,460,801 (GRCm39) Y1718N probably damaging Het
Or4c58 A G 2: 89,675,011 (GRCm39) F102S probably damaging Het
Or4d2 T A 11: 87,784,511 (GRCm39) K80* probably null Het
Or51f5 C T 7: 102,424,136 (GRCm39) A135V probably benign Het
Or5an9 T A 19: 12,187,824 (GRCm39) I298N probably damaging Het
Or6c8b G T 10: 128,882,364 (GRCm39) D189E probably damaging Het
Pcdha4 C A 18: 37,087,890 (GRCm39) A691E probably benign Het
Pde6a T G 18: 61,364,438 (GRCm39) F165V probably damaging Het
Ptpn14 A T 1: 189,578,561 (GRCm39) M340L probably benign Het
Rnasel G T 1: 153,630,890 (GRCm39) E469* probably null Het
Rsph3a T G 17: 8,164,790 (GRCm39) L50R probably benign Het
Rusc2 A G 4: 43,423,975 (GRCm39) Y1043C probably damaging Het
Serpinb6b A T 13: 33,161,541 (GRCm39) K86* probably null Het
Serpine1 T C 5: 137,092,063 (GRCm39) T392A probably benign Het
Shcbp1 A T 8: 4,794,529 (GRCm39) D421E probably damaging Het
Slc24a1 A G 9: 64,855,863 (GRCm39) V348A unknown Het
Slc26a7 A G 4: 14,506,621 (GRCm39) F605L probably benign Het
Slc66a1 A T 4: 139,027,655 (GRCm39) L229Q probably damaging Het
Spag17 A C 3: 99,963,588 (GRCm39) E1102A possibly damaging Het
Stab2 A G 10: 86,683,989 (GRCm39) V2390A probably benign Het
Stk11 A G 10: 79,961,883 (GRCm39) I35V probably benign Het
Stk24 T C 14: 121,531,693 (GRCm39) D321G possibly damaging Het
Tbx4 A T 11: 85,801,994 (GRCm39) N209I possibly damaging Het
Tmem225 T C 9: 40,060,681 (GRCm39) L80P probably damaging Het
Tnfrsf4 C T 4: 156,098,380 (GRCm39) T17I probably benign Het
Traf3ip1 G A 1: 91,429,037 (GRCm39) R268Q probably benign Het
Trhde T A 10: 114,636,497 (GRCm39) I237F probably benign Het
Ugt2a1 A T 5: 87,633,915 (GRCm39) W231R probably damaging Het
Vash1 ACTGCTGCTGCTGCTGCTGC ACTGCTGCTGCTGCTGC 12: 86,726,831 (GRCm39) probably benign Het
Vps16 T A 2: 130,284,305 (GRCm39) D685E probably benign Het
Washc4 A G 10: 83,409,657 (GRCm39) D602G probably damaging Het
Wdr59 A G 8: 112,211,816 (GRCm39) L377P possibly damaging Het
Wdr81 T C 11: 75,339,896 (GRCm39) E1364G 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
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
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'- ACCACACCCTGATCTTTGGC -3'

Sequencing Primer
(F):5'- GCAAGAGAAATGAACTTCAGGAAAC -3'
(R):5'- AGGATCTCCAATGTGTTCTACCAG -3'
Posted On 2016-10-24