Incidental Mutation 'R0138:Cyp46a1'
ID 22123
Institutional Source Beutler Lab
Gene Symbol Cyp46a1
Ensembl Gene ENSMUSG00000021259
Gene Name cytochrome P450, family 46, subfamily a, polypeptide 1
Synonyms cholestrol 24-hydroxylase, Cyp46
MMRRC Submission 038423-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R0138 (G1)
Quality Score 225
Status Validated
Chromosome 12
Chromosomal Location 108300640-108328493 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 108317470 bp (GRCm39)
Zygosity Heterozygous
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]
AlphaFold Q9WVK8
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: 121,899,098 (GRCm39) N693K probably damaging Het
Adgrl3 T A 5: 81,841,454 (GRCm39) V845D probably damaging Het
Anxa8 T A 14: 33,819,896 (GRCm39) F269Y probably benign Het
Anxa8 T A 14: 33,819,897 (GRCm39) F295L possibly damaging Het
Aox4 C G 1: 58,268,025 (GRCm39) L202V probably damaging Het
Ap3s2 A G 7: 79,559,617 (GRCm39) V104A probably benign Het
Aqp3 G A 4: 41,094,843 (GRCm39) probably benign Het
Arhgef26 C T 3: 62,355,680 (GRCm39) H751Y probably benign Het
Asic4 A T 1: 75,446,331 (GRCm39) Q291L possibly damaging Het
Bap1 T C 14: 30,978,681 (GRCm39) Y31H probably damaging Het
Brf1 A T 12: 112,924,759 (GRCm39) V655D probably damaging Het
Cebpz A G 17: 79,238,820 (GRCm39) S663P probably benign Het
Ces2h A G 8: 105,744,693 (GRCm39) D357G probably benign Het
Cfap36 T C 11: 29,194,073 (GRCm39) T90A probably benign Het
Ciita A T 16: 10,330,134 (GRCm39) D803V probably damaging Het
Clnk C A 5: 38,931,951 (GRCm39) probably benign Het
Cyp4f13 A G 17: 33,160,080 (GRCm39) I98T possibly damaging Het
Def8 G A 8: 124,183,234 (GRCm39) A278T probably damaging Het
Dll3 T A 7: 28,000,746 (GRCm39) D103V possibly damaging Het
Dnai1 T A 4: 41,629,814 (GRCm39) M446K possibly damaging Het
Dppa4 A T 16: 48,111,425 (GRCm39) T85S probably benign Het
Eif4g1 A T 16: 20,494,095 (GRCm39) H57L probably damaging Het
Fmnl3 G C 15: 99,220,619 (GRCm39) probably benign Het
Fn1 T A 1: 71,663,269 (GRCm39) Q1073L possibly damaging Het
Foxp4 T C 17: 48,180,104 (GRCm39) D599G unknown Het
Frrs1 T C 3: 116,675,456 (GRCm39) V128A possibly damaging Het
Gcfc2 G A 6: 81,926,935 (GRCm39) D608N probably damaging Het
Gm1043 T C 5: 37,350,317 (GRCm39) probably benign Het
Gm5148 T C 3: 37,768,926 (GRCm39) E98G probably benign Het
Gpr141 T C 13: 19,936,428 (GRCm39) I116V probably benign Het
Hic1 T C 11: 75,058,169 (GRCm39) N240S probably damaging Het
Hpx G A 7: 105,241,445 (GRCm39) T322I probably damaging Het
Hs3st4 A T 7: 123,996,416 (GRCm39) M361L probably benign Het
Ifrd1 A G 12: 40,257,129 (GRCm39) probably benign Het
Ino80 G A 2: 119,213,441 (GRCm39) R1249C probably damaging Het
Klk1b21 T A 7: 43,755,319 (GRCm39) C173S probably damaging Het
Krt25 A T 11: 99,213,524 (GRCm39) V65E probably benign Het
Lrrc15 A T 16: 30,092,267 (GRCm39) D357E possibly damaging Het
Lrrd1 T A 5: 3,901,345 (GRCm39) V550E probably benign Het
Macf1 A G 4: 123,334,540 (GRCm39) Y1490H probably damaging Het
Macrod1 A G 19: 7,174,281 (GRCm39) probably benign Het
Mcm5 T A 8: 75,847,508 (GRCm39) V435D probably damaging Het
Mctp1 C T 13: 76,975,831 (GRCm39) R478C probably damaging Het
Med10 T C 13: 69,959,817 (GRCm39) probably benign Het
Mrpl4 T C 9: 20,919,888 (GRCm39) Y280H probably benign Het
Msrb3 T C 10: 120,687,892 (GRCm39) E61G probably damaging Het
Myo1c T C 11: 75,551,827 (GRCm39) Y337H possibly damaging Het
Myo7b T A 18: 32,143,204 (GRCm39) T165S probably damaging Het
Myrfl T A 10: 116,685,138 (GRCm39) R81W probably damaging Het
Neil1 T C 9: 57,051,030 (GRCm39) probably benign Het
Neto2 A G 8: 86,367,673 (GRCm39) I357T possibly damaging Het
Nfat5 C T 8: 108,065,707 (GRCm39) R156W probably damaging Het
Nkx6-3 T C 8: 23,643,607 (GRCm39) S3P probably benign Het
Or52h7 A T 7: 104,214,210 (GRCm39) I261L probably benign Het
Plce1 T C 19: 38,512,863 (GRCm39) I54T possibly damaging Het
Prex2 A T 1: 11,355,267 (GRCm39) probably benign Het
Psapl1 T A 5: 36,361,975 (GRCm39) V189E probably damaging Het
Ptdss2 T G 7: 140,735,232 (GRCm39) probably benign Het
Rnf213 T C 11: 119,307,322 (GRCm39) C661R probably benign Het
Rpap1 T C 2: 119,595,380 (GRCm39) probably null Het
Rrp1b A G 17: 32,279,426 (GRCm39) T696A probably benign Het
Sacm1l T A 9: 123,377,982 (GRCm39) H87Q probably benign Het
Serpinb11 T A 1: 107,305,260 (GRCm39) M212K probably damaging Het
Tbc1d22a C A 15: 86,183,885 (GRCm39) T248K probably damaging Het
Tcerg1 C T 18: 42,701,679 (GRCm39) probably benign Het
Tpst1 T A 5: 130,130,627 (GRCm39) H32Q probably damaging Het
Tsc2 A T 17: 24,818,600 (GRCm39) V1412E possibly damaging Het
Usp19 C A 9: 108,378,514 (GRCm39) P1326Q possibly damaging Het
Vmn1r235 T A 17: 21,482,596 (GRCm39) M307K probably damaging Het
Vmn2r58 T A 7: 41,487,048 (GRCm39) T616S probably damaging Het
Vps13a G A 19: 16,637,863 (GRCm39) T2406I possibly damaging Het
Zbtb26 T A 2: 37,326,053 (GRCm39) M328L probably benign Het
Zp2 A G 7: 119,736,423 (GRCm39) F340S probably damaging Het
Other mutations in Cyp46a1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01622:Cyp46a1 APN 12 108,318,234 (GRCm39) missense possibly damaging 0.78
IGL01623:Cyp46a1 APN 12 108,318,234 (GRCm39) missense possibly damaging 0.78
IGL01804:Cyp46a1 APN 12 108,321,745 (GRCm39) missense probably benign 0.44
IGL02069:Cyp46a1 APN 12 108,312,394 (GRCm39) missense probably benign 0.18
IGL02900:Cyp46a1 APN 12 108,309,350 (GRCm39) missense probably damaging 1.00
IGL02969:Cyp46a1 APN 12 108,309,296 (GRCm39) missense probably damaging 1.00
PIT4651001:Cyp46a1 UTSW 12 108,319,367 (GRCm39) missense probably benign 0.17
R1572:Cyp46a1 UTSW 12 108,318,198 (GRCm39) missense probably null 0.97
R1879:Cyp46a1 UTSW 12 108,319,385 (GRCm39) missense probably damaging 1.00
R2280:Cyp46a1 UTSW 12 108,321,730 (GRCm39) missense probably damaging 1.00
R3879:Cyp46a1 UTSW 12 108,324,389 (GRCm39) missense probably benign 0.14
R4674:Cyp46a1 UTSW 12 108,324,345 (GRCm39) missense probably damaging 1.00
R4717:Cyp46a1 UTSW 12 108,318,285 (GRCm39) critical splice donor site probably null
R6224:Cyp46a1 UTSW 12 108,327,819 (GRCm39) missense probably damaging 1.00
R6473:Cyp46a1 UTSW 12 108,321,734 (GRCm39) missense possibly damaging 0.87
R6539:Cyp46a1 UTSW 12 108,319,416 (GRCm39) splice site probably null
R7253:Cyp46a1 UTSW 12 108,318,255 (GRCm39) missense probably benign 0.16
R8208:Cyp46a1 UTSW 12 108,318,171 (GRCm39) critical splice acceptor site probably null
R8805:Cyp46a1 UTSW 12 108,327,462 (GRCm39) missense probably damaging 1.00
R8951:Cyp46a1 UTSW 12 108,312,348 (GRCm39) missense possibly damaging 0.90
R8992:Cyp46a1 UTSW 12 108,324,366 (GRCm39) missense possibly damaging 0.91
Predicted Primers PCR Primer
(F):5'- ACCATTAAGGCAGGGGTGCATTG -3'
(R):5'- CCTCATTACCAAGTCCACTGTGACC -3'

Sequencing Primer
(F):5'- TGCATTGGGGGCAATGG -3'
(R):5'- GAGAACATCCACAGTTGCCTTG -3'
Posted On 2013-04-12