Incidental Mutation 'R0138:Cyp46a1'
ID22123
Institutional Source Beutler Lab
Gene Symbol Cyp46a1
Ensembl Gene ENSMUSG00000021259
Gene Namecytochrome P450, family 46, subfamily a, polypeptide 1
Synonymscholestrol 24-hydroxylase, Cyp46
MMRRC Submission 038423-MU
Accession Numbers
Is this an essential gene? Non essential (E-score: 0.000) question?
Stock #R0138 (G1)
Quality Score225
Status Validated
Chromosome12
Chromosomal Location108334381-108362234 bp(+) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) A to G at 108351211 bp
ZygosityHeterozygous
Amino Acid Change Asparagine to Serine at position 158 (N158S)
Ref Sequence ENSEMBL: ENSMUSP00000021684 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000021684] [ENSMUST00000221708]
Predicted Effect probably damaging
Transcript: ENSMUST00000021684
AA Change: N158S

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000021684
Gene: ENSMUSG00000021259
AA Change: N158S

DomainStartEndE-ValueType
low complexity region 4 18 N/A INTRINSIC
Pfam:p450 34 484 1.7e-86 PFAM
low complexity region 493 499 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000221708
Predicted Effect noncoding transcript
Transcript: ENSMUST00000222240
Predicted Effect noncoding transcript
Transcript: ENSMUST00000222902
Meta Mutation Damage Score 0.1670 question?
Coding Region Coverage
  • 1x: 99.0%
  • 3x: 98.3%
  • 10x: 96.4%
  • 20x: 92.8%
Validation Efficiency 97% (76/78)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic reticulum protein is expressed in the brain, where it converts cholesterol to 24S-hydroxycholesterol. While cholesterol cannot pass the blood-brain barrier, 24S-hydroxycholesterol can be secreted in the brain into the circulation to be returned to the liver for catabolism. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygouse for deletions in this gene are essentially normal. Levels of 24(s)-hydroxycholesterol are reduced in serum and in the brain. Cholesterol synthesis in the brain is reduced 40%. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 73 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca4 T A 3: 122,105,449 N693K probably damaging Het
Adgrl3 T A 5: 81,693,607 V845D probably damaging Het
Anxa8 T A 14: 34,097,939 F269Y probably benign Het
Anxa8 T A 14: 34,097,940 F295L possibly damaging Het
Aox4 C G 1: 58,228,866 L202V probably damaging Het
Ap3s2 A G 7: 79,909,869 V104A probably benign Het
Aqp3 G A 4: 41,094,843 probably benign Het
Arhgef26 C T 3: 62,448,259 H751Y probably benign Het
Asic4 A T 1: 75,469,687 Q291L possibly damaging Het
Bap1 T C 14: 31,256,724 Y31H probably damaging Het
Brf1 A T 12: 112,961,139 V655D probably damaging Het
Cebpz A G 17: 78,931,391 S663P probably benign Het
Ces2h A G 8: 105,018,061 D357G probably benign Het
Cfap36 T C 11: 29,244,073 T90A probably benign Het
Ciita A T 16: 10,512,270 D803V probably damaging Het
Clnk C A 5: 38,774,608 probably benign Het
Cyp4f13 A G 17: 32,941,106 I98T possibly damaging Het
Def8 G A 8: 123,456,495 A278T probably damaging Het
Dll3 T A 7: 28,301,321 D103V possibly damaging Het
Dnaic1 T A 4: 41,629,814 M446K possibly damaging Het
Dppa4 A T 16: 48,291,062 T85S probably benign Het
Eif4g1 A T 16: 20,675,345 H57L probably damaging Het
Fmnl3 G C 15: 99,322,738 probably benign Het
Fn1 T A 1: 71,624,110 Q1073L possibly damaging Het
Foxp4 T C 17: 47,869,179 D599G unknown Het
Frrs1 T C 3: 116,881,807 V128A possibly damaging Het
Gcfc2 G A 6: 81,949,954 D608N probably damaging Het
Gm1043 T C 5: 37,192,973 probably benign Het
Gm5148 T C 3: 37,714,777 E98G probably benign Het
Gpr141 T C 13: 19,752,258 I116V probably benign Het
Hic1 T C 11: 75,167,343 N240S probably damaging Het
Hpx G A 7: 105,592,238 T322I probably damaging Het
Hs3st4 A T 7: 124,397,193 M361L probably benign Het
Ifrd1 A G 12: 40,207,130 probably benign Het
Ino80 G A 2: 119,382,960 R1249C probably damaging Het
Klk1b21 T A 7: 44,105,895 C173S probably damaging Het
Krt25 A T 11: 99,322,698 V65E probably benign Het
Lrrc15 A T 16: 30,273,449 D357E possibly damaging Het
Lrrd1 T A 5: 3,851,345 V550E probably benign Het
Macf1 A G 4: 123,440,747 Y1490H probably damaging Het
Macrod1 A G 19: 7,196,916 probably benign Het
Mcm5 T A 8: 75,120,880 V435D probably damaging Het
Mctp1 C T 13: 76,827,712 R478C probably damaging Het
Med10 T C 13: 69,811,698 probably benign Het
Mrpl4 T C 9: 21,008,592 Y280H probably benign Het
Msrb3 T C 10: 120,851,987 E61G probably damaging Het
Myo1c T C 11: 75,661,001 Y337H possibly damaging Het
Myo7b T A 18: 32,010,151 T165S probably damaging Het
Myrfl T A 10: 116,849,233 R81W probably damaging Het
Neil1 T C 9: 57,143,746 probably benign Het
Neto2 A G 8: 85,641,044 I357T possibly damaging Het
Nfat5 C T 8: 107,339,075 R156W probably damaging Het
Nkx6-3 T C 8: 23,153,591 S3P probably benign Het
Olfr652 A T 7: 104,565,003 I261L probably benign Het
Plce1 T C 19: 38,524,419 I54T possibly damaging Het
Prex2 A T 1: 11,285,043 probably benign Het
Psapl1 T A 5: 36,204,631 V189E probably damaging Het
Ptdss2 T G 7: 141,155,319 probably benign Het
Rnf213 T C 11: 119,416,496 C661R probably benign Het
Rpap1 T C 2: 119,764,899 probably null Het
Rrp1b A G 17: 32,060,452 T696A probably benign Het
Sacm1l T A 9: 123,548,917 H87Q probably benign Het
Serpinb11 T A 1: 107,377,530 M212K probably damaging Het
Tbc1d22a C A 15: 86,299,684 T248K probably damaging Het
Tcerg1 C T 18: 42,568,614 probably benign Het
Tpst1 T A 5: 130,101,786 H32Q probably damaging Het
Tsc2 A T 17: 24,599,626 V1412E possibly damaging Het
Usp19 C A 9: 108,501,315 P1326Q possibly damaging Het
Vmn1r235 T A 17: 21,262,334 M307K probably damaging Het
Vmn2r58 T A 7: 41,837,624 T616S probably damaging Het
Vps13a G A 19: 16,660,499 T2406I possibly damaging Het
Zbtb26 T A 2: 37,436,041 M328L probably benign Het
Zp2 A G 7: 120,137,200 F340S probably damaging Het
Other mutations in Cyp46a1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01622:Cyp46a1 APN 12 108351975 missense possibly damaging 0.78
IGL01623:Cyp46a1 APN 12 108351975 missense possibly damaging 0.78
IGL01804:Cyp46a1 APN 12 108355486 missense probably benign 0.44
IGL02069:Cyp46a1 APN 12 108346135 missense probably benign 0.18
IGL02900:Cyp46a1 APN 12 108343091 missense probably damaging 1.00
IGL02969:Cyp46a1 APN 12 108343037 missense probably damaging 1.00
PIT4651001:Cyp46a1 UTSW 12 108353108 missense probably benign 0.17
R1572:Cyp46a1 UTSW 12 108351939 missense probably null 0.97
R1879:Cyp46a1 UTSW 12 108353126 missense probably damaging 1.00
R2280:Cyp46a1 UTSW 12 108355471 missense probably damaging 1.00
R3879:Cyp46a1 UTSW 12 108358130 missense probably benign 0.14
R4674:Cyp46a1 UTSW 12 108358086 missense probably damaging 1.00
R4717:Cyp46a1 UTSW 12 108352026 critical splice donor site probably null
R6224:Cyp46a1 UTSW 12 108361560 missense probably damaging 1.00
R6473:Cyp46a1 UTSW 12 108355475 missense possibly damaging 0.87
R6539:Cyp46a1 UTSW 12 108353157 splice site probably null
R7253:Cyp46a1 UTSW 12 108351996 missense probably benign 0.16
Predicted Primers PCR Primer
(F):5'- ACCATTAAGGCAGGGGTGCATTG -3'
(R):5'- CCTCATTACCAAGTCCACTGTGACC -3'

Sequencing Primer
(F):5'- TGCATTGGGGGCAATGG -3'
(R):5'- GAGAACATCCACAGTTGCCTTG -3'
Posted On2013-04-12