Incidental Mutation 'R7273:Npc1l1'
ID 565409
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 045357-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.098) question?
Stock # R7273 (G1)
Quality Score 225.009
Status Validated
Chromosome 11
Chromosomal Location 6161013-6180143 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 6168320 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Phenylalanine to Serine at position 957 (F957S)
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: F957S

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: F957S

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 0.9304 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.8%
  • 20x: 99.3%
Validation Efficiency 100% (49/49)
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: 47 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Apol10a A T 15: 77,373,068 (GRCm39) I235F probably damaging Het
Aspn A T 13: 49,712,352 (GRCm39) E222D probably benign Het
Cfap221 A T 1: 119,881,948 (GRCm39) V280D possibly damaging Het
Chrd G A 16: 20,560,316 (GRCm39) R922Q probably benign Het
Cnga4 T A 7: 105,056,172 (GRCm39) V361E probably damaging Het
Col15a1 T A 4: 47,284,467 (GRCm39) probably null Het
Col6a4 A G 9: 105,877,656 (GRCm39) V2107A possibly damaging Het
Eea1 G T 10: 95,825,493 (GRCm39) V63F probably benign Het
Eml1 A G 12: 108,504,432 (GRCm39) H797R possibly damaging Het
Il1r2 A G 1: 40,151,167 (GRCm39) T141A probably benign Het
Il6st T C 13: 112,631,832 (GRCm39) V457A probably benign Het
Kif19b T A 5: 140,461,767 (GRCm39) V523E probably damaging Het
Lrrc56 T C 7: 140,789,578 (GRCm39) C532R probably benign Het
Lrrn4 T C 2: 132,721,749 (GRCm39) S23G unknown Het
Mapk8ip3 A T 17: 25,125,148 (GRCm39) D498E probably benign Het
Mcam T C 9: 44,052,241 (GRCm39) F584S possibly damaging Het
Mdga1 A T 17: 30,188,912 (GRCm39) D50E unknown Het
Mga T C 2: 119,765,695 (GRCm39) S1320P probably damaging Het
Muc5b G A 7: 141,405,307 (GRCm39) G905D unknown Het
Ncor2 T C 5: 125,100,687 (GRCm39) N1297S Het
Nisch A G 14: 30,896,364 (GRCm39) V946A unknown Het
Nuggc A G 14: 65,857,057 (GRCm39) N402S probably damaging Het
Nup210l A G 3: 90,025,854 (GRCm39) T159A probably benign Het
Or10g6 A T 9: 39,933,961 (GRCm39) I91F probably benign Het
Otud1 A G 2: 19,663,873 (GRCm39) D334G probably damaging Het
Pclo T C 5: 14,731,608 (GRCm39) V3370A unknown Het
Prdm16 A G 4: 154,429,910 (GRCm39) L353P probably damaging Het
Prepl A C 17: 85,389,420 (GRCm39) V128G probably benign Het
Pum1 T C 4: 130,478,791 (GRCm39) V568A probably damaging Het
Rab10 G T 12: 3,306,891 (GRCm39) S101R probably benign Het
Rfx3 C T 19: 27,779,858 (GRCm39) R435Q probably damaging Het
Rnf213 A T 11: 119,322,582 (GRCm39) probably null Het
Sema5a A G 15: 32,417,608 (GRCm39) D26G probably benign Het
Slc49a3 T C 5: 108,589,857 (GRCm39) D515G probably benign Het
Spata31d1b G A 13: 59,865,446 (GRCm39) V865I probably benign Het
Sycp3 A T 10: 88,305,428 (GRCm39) Q176H probably damaging Het
Tdpoz8 G T 3: 92,981,475 (GRCm39) M90I probably damaging Het
Tmprss11d A T 5: 86,485,098 (GRCm39) V102D probably damaging Het
Top1mt A G 15: 75,535,931 (GRCm39) V457A probably benign Het
Tubal3 T A 13: 3,980,675 (GRCm39) I129N probably damaging Het
Ubr3 G A 2: 69,809,677 (GRCm39) D1217N probably damaging Het
Uggt1 A G 1: 36,201,302 (GRCm39) I1146T probably damaging Het
Umod T C 7: 119,076,250 (GRCm39) Q172R probably benign Het
Uqcc5 G T 14: 30,846,555 (GRCm39) R55S probably damaging Het
Zdbf2 C T 1: 63,342,563 (GRCm39) A314V possibly damaging Het
Zfp787 A T 7: 6,136,039 (GRCm39) C71S possibly damaging Het
Zhx2 C T 15: 57,686,824 (GRCm39) A731V 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
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
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'- ATGGGAGACTGAGAGCCTTTC -3'
(R):5'- TCAGTAAGTGGTTGGTCTCCC -3'

Sequencing Primer
(F):5'- GGAGACTGAGAGCCTTTCTTTTCTC -3'
(R):5'- GTTGGTCTCCCCGACACC -3'
Posted On 2019-06-26