Incidental Mutation 'R7383:Npc1l1'
ID 572888
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 045465-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.098) question?
Stock # R7383 (G1)
Quality Score 225.009
Status Not validated
Chromosome 11
Chromosomal Location 6161013-6180143 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 6167777 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Alanine at position 1005 (T1005A)
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: T1005A

PolyPhen 2 Score 0.304 (Sensitivity: 0.90; Specificity: 0.89)
SMART Domains Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: T1005A

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: 100.0%
  • 3x: 100.0%
  • 10x: 99.8%
  • 20x: 99.3%
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: 71 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Aebp1 T A 11: 5,818,548 (GRCm39) I511N probably damaging Het
Ap5m1 T G 14: 49,311,653 (GRCm39) V241G possibly damaging Het
BC049715 T A 6: 136,817,453 (GRCm39) I231N probably damaging Het
Bckdhb T G 9: 83,835,766 (GRCm39) V90G possibly damaging Het
Cep20 TTGTG TTG 16: 14,118,009 (GRCm39) probably null Het
Chd8 T C 14: 52,452,776 (GRCm39) I1248V probably damaging Het
Ckap2l A T 2: 129,111,172 (GRCm39) M675K possibly damaging Het
Ckap4 A T 10: 84,364,148 (GRCm39) V305E probably damaging Het
Clasrp C A 7: 19,319,198 (GRCm39) R489L unknown Het
Col24a1 A G 3: 145,004,599 (GRCm39) I26V probably benign Het
Cort C T 4: 149,209,861 (GRCm39) A64T possibly damaging Het
Dmkn T A 7: 30,464,793 (GRCm39) N255K unknown Het
Dph2 A T 4: 117,748,566 (GRCm39) L69Q probably damaging Het
Fbxo11 A G 17: 88,310,282 (GRCm39) I432T Het
Fgd3 T C 13: 49,421,785 (GRCm39) K531R possibly damaging Het
Fgd5 A G 6: 91,964,099 (GRCm39) K111E probably benign Het
Gdf6 T A 4: 9,859,537 (GRCm39) D206E probably benign Het
Gtpbp1 T A 15: 79,600,354 (GRCm39) L429Q probably damaging Het
Hk2 A G 6: 82,726,276 (GRCm39) F90S probably damaging Het
Hrnr A T 3: 93,239,098 (GRCm39) Q3112L unknown Het
Hsd17b4 A C 18: 50,297,917 (GRCm39) K402T probably benign Het
Htr1f T C 16: 64,747,206 (GRCm39) T29A probably benign Het
Ikbkb C A 8: 23,159,066 (GRCm39) A471S probably benign Het
Inpp5f A G 7: 128,296,310 (GRCm39) D887G probably damaging Het
Ipo9 A G 1: 135,316,411 (GRCm39) L805P probably damaging Het
Jmjd1c A T 10: 67,025,537 (GRCm39) N118I probably benign Het
Kif26b T G 1: 178,358,275 (GRCm39) C129G probably damaging Het
Mga G A 2: 119,790,821 (GRCm39) A2236T probably damaging Het
Micu2 T C 14: 58,154,810 (GRCm39) Q405R possibly damaging Het
Myo1e T A 9: 70,204,577 (GRCm39) V59D probably damaging Het
Nav3 A G 10: 109,552,532 (GRCm39) I1770T probably damaging Het
Ndufa10 A T 1: 92,392,183 (GRCm39) I190N probably damaging Het
Niban3 A C 8: 72,056,470 (GRCm39) E390A possibly damaging Het
Npat T A 9: 53,474,078 (GRCm39) H623Q probably benign Het
Or10ag58 A G 2: 87,265,721 (GRCm39) S297G possibly damaging Het
Or14c39 A T 7: 86,343,960 (GRCm39) I99F probably damaging Het
Or1e22 A G 11: 73,376,715 (GRCm39) *312Q probably null Het
Or2b4 A G 17: 38,116,972 (GRCm39) K312R probably benign Het
Or2w3 T C 11: 58,557,011 (GRCm39) S209P possibly damaging Het
Or5t7 A G 2: 86,507,263 (GRCm39) V138A possibly damaging Het
Or8s8 C G 15: 98,354,578 (GRCm39) P129R probably damaging Het
Pafah1b2 C T 9: 45,880,147 (GRCm39) G177R probably benign Het
Phc1 A G 6: 122,300,317 (GRCm39) S521P unknown Het
Plpp2 A T 10: 79,366,841 (GRCm39) L25Q probably null Het
Plxna4 A G 6: 32,129,734 (GRCm39) probably null Het
Ppl G T 16: 4,915,835 (GRCm39) P576Q probably damaging Het
Rab38 T C 7: 88,079,637 (GRCm39) Y10H possibly damaging Het
Rbfox1 G A 16: 6,887,899 (GRCm39) G13S probably benign Het
Rhot1 C G 11: 80,114,760 (GRCm39) P56R probably damaging Het
Sipa1l2 A G 8: 126,174,385 (GRCm39) W1298R probably damaging Het
Slc16a14 G A 1: 84,890,292 (GRCm39) H338Y probably damaging Het
Slc8a3 T G 12: 81,362,579 (GRCm39) Y80S probably damaging Het
Slco6c1 A T 1: 97,003,608 (GRCm39) Y513* probably null Het
Smarcd2 A G 11: 106,155,602 (GRCm39) C405R probably damaging Het
Szt2 G A 4: 118,222,411 (GRCm39) R3198* probably null Het
Tmeff1 T A 4: 48,636,841 (GRCm39) C180S probably damaging Het
Tmem132a A T 19: 10,844,358 (GRCm39) M80K probably benign Het
Tnfsf12 A G 11: 69,577,892 (GRCm39) V175A probably damaging Het
Tnpo2 G A 8: 85,776,748 (GRCm39) R485H probably damaging Het
Togaram2 A T 17: 72,007,512 (GRCm39) I354F probably damaging Het
Uchl5 T A 1: 143,659,753 (GRCm39) S42R probably benign Het
Virma C A 4: 11,514,026 (GRCm39) L627I probably damaging Het
Vmn2r12 A T 5: 109,240,684 (GRCm39) I143K probably benign Het
Vmn2r95 T G 17: 18,660,734 (GRCm39) V382G probably benign Het
Wipf3 G T 6: 54,462,263 (GRCm39) A158S probably benign Het
Ylpm1 T G 12: 85,091,242 (GRCm39) S1809A possibly damaging Het
Zdhhc5 A T 2: 84,524,748 (GRCm39) C191S probably benign Het
Zer1 G A 2: 30,001,253 (GRCm39) R84C probably damaging Het
Zfhx2 A T 14: 55,305,710 (GRCm39) V991D probably benign Het
Zscan4b C A 7: 10,637,960 (GRCm39) M61I possibly damaging Het
Zswim2 A T 2: 83,745,672 (GRCm39) S589T possibly 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
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
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'- AGACCTTGTCCTGTCAGTCC -3'
(R):5'- CATTTCTTGACCCCACAACTGG -3'

Sequencing Primer
(F):5'- TCACTGTGCCCCAGAAAGG -3'
(R):5'- GGGGTGGCAGGTGTAAACCTC -3'
Posted On 2019-09-13