Incidental Mutation 'R8951:Cyp46a1'
ID 681663
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 068788-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R8951 (G1)
Quality Score 225.009
Status Validated
Chromosome 12
Chromosomal Location 108300640-108328493 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to C at 108312348 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Arginine to Serine at position 119 (R119S)
Ref Sequence ENSEMBL: ENSMUSP00000021684 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000021684] [ENSMUST00000221708]
AlphaFold Q9WVK8
Predicted Effect possibly damaging
Transcript: ENSMUST00000021684
AA Change: R119S

PolyPhen 2 Score 0.903 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000021684
Gene: ENSMUSG00000021259
AA Change: R119S

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
Meta Mutation Damage Score 0.6544 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.7%
  • 20x: 99.2%
Validation Efficiency 99% (73/74)
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: 75 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adam11 T C 11: 102,665,193 (GRCm39) probably null Het
Adcy6 A T 15: 98,502,140 (GRCm39) V158E possibly damaging Het
Adgrg3 T C 8: 95,761,362 (GRCm39) probably benign Het
Arsb T C 13: 93,944,124 (GRCm39) S272P probably damaging Het
Asb10 A C 5: 24,742,952 (GRCm39) C260W probably damaging Het
Atp13a1 A G 8: 70,246,484 (GRCm39) D158G probably benign Het
Bcl6 T C 16: 23,793,704 (GRCm39) E81G probably damaging Het
C7 A T 15: 5,032,231 (GRCm39) V660E probably benign Het
Cacna1c T C 6: 118,590,300 (GRCm39) D1401G probably damaging Het
Ccp110 A G 7: 118,321,015 (GRCm39) I223M possibly damaging Het
Cilp A G 9: 65,180,220 (GRCm39) E187G probably benign Het
Cmc2 T C 8: 117,637,904 (GRCm39) N15S probably damaging Het
Cnnm3 T A 1: 36,558,019 (GRCm39) probably benign Het
Col27a1 T G 4: 63,191,311 (GRCm39) M828R possibly damaging Het
Cpm C T 10: 117,511,938 (GRCm39) P294L probably damaging Het
Cpt1a G C 19: 3,412,211 (GRCm39) A228P probably benign Het
Ctbp1 A G 5: 33,416,679 (GRCm39) V43A probably damaging Het
Cylc2 A T 4: 51,229,469 (GRCm39) E270D unknown Het
Dctn3 A T 4: 41,719,845 (GRCm39) I87N probably damaging Het
Dhdds C T 4: 133,719,857 (GRCm39) V25I possibly damaging Het
Entpd1 A C 19: 40,727,319 (GRCm39) N489T probably damaging Het
Fam110a T C 2: 151,812,461 (GRCm39) D103G probably damaging Het
Foxo6 T A 4: 120,125,133 (GRCm39) Q554L unknown Het
Gbp5 T A 3: 142,206,481 (GRCm39) M55K probably damaging Het
Gm20730 T C 6: 43,058,638 (GRCm39) Y58C possibly damaging Het
Grip1 T A 10: 119,874,509 (GRCm39) S679T possibly damaging Het
Gtdc1 A C 2: 44,679,030 (GRCm39) probably benign Het
Idh2 TCCCAGG T 7: 79,748,079 (GRCm39) probably benign Het
Igha T A 12: 113,222,684 (GRCm39) N246Y Het
Ighg2b T A 12: 113,270,926 (GRCm39) T104S probably benign Het
Ighmbp2 C T 19: 3,318,726 (GRCm39) W450* probably null Het
Ipo11 T C 13: 106,978,690 (GRCm39) E839G possibly damaging Het
Iqce T C 5: 140,675,578 (GRCm39) D207G probably damaging Het
Irgm2 T C 11: 58,110,408 (GRCm39) V45A possibly damaging Het
Itga1 C T 13: 115,107,027 (GRCm39) W1021* probably null Het
Itga3 T C 11: 94,944,911 (GRCm39) Y799C probably damaging Het
Klf1 T C 8: 85,629,912 (GRCm39) S246P possibly damaging Het
Kras A T 6: 145,166,338 (GRCm39) M188K probably benign Het
Lacc1 C T 14: 77,272,613 (GRCm39) C61Y probably benign Het
Lect2 T A 13: 56,690,822 (GRCm39) probably benign Het
Leng9 G A 7: 4,152,782 (GRCm39) probably benign Het
Lhx9 A G 1: 138,769,704 (GRCm39) C6R probably damaging Het
Matn3 T A 12: 9,002,172 (GRCm39) I128K probably damaging Het
Ndst1 T C 18: 60,830,196 (GRCm39) E638G probably benign Het
Nell2 A T 15: 95,139,424 (GRCm39) C603S probably damaging Het
Nicn1 C T 9: 108,171,708 (GRCm39) R163C possibly damaging Het
Oas1h T G 5: 121,000,657 (GRCm39) F89C probably damaging Het
Or4d10c A T 19: 12,066,056 (GRCm39) Y33* probably null Het
Or52l1 A G 7: 104,829,638 (GRCm39) V294A probably damaging Het
Or5b101 T A 19: 13,004,827 (GRCm39) S289C Het
Or5d45 C T 2: 88,153,975 (GRCm39) G25S probably damaging Het
P2ry2 G A 7: 100,647,228 (GRCm39) T359I probably damaging Het
Pbxip1 T A 3: 89,352,864 (GRCm39) V170E probably benign Het
Pcdhb20 T A 18: 37,639,146 (GRCm39) N557K probably damaging Het
Pdilt A G 7: 119,099,611 (GRCm39) V219A possibly damaging Het
Plec G T 15: 76,067,310 (GRCm39) S1149* probably null Het
Pnkp C T 7: 44,507,617 (GRCm39) T61I possibly damaging Het
Polr1f G T 12: 33,487,867 (GRCm39) E261* probably null Het
Prss56 T A 1: 87,115,749 (GRCm39) V541D probably damaging Het
Rab40c A G 17: 26,138,407 (GRCm39) V25A probably damaging Het
Rgs8 A T 1: 153,546,567 (GRCm39) H22L probably damaging Het
Rsf1 ATGGCG ATGGCGACGGTGGCG 7: 97,229,111 (GRCm39) probably benign Het
Slc1a2 T C 2: 102,586,353 (GRCm39) V319A probably damaging Het
Sp140l2 G A 1: 85,224,671 (GRCm39) S288L possibly damaging Het
Spata18 A T 5: 73,828,572 (GRCm39) I378F probably damaging Het
Speer1i T A 5: 11,092,799 (GRCm39) Y79* probably null Het
Stag1 T C 9: 100,762,854 (GRCm39) V485A probably damaging Het
Tas2r104 T A 6: 131,662,569 (GRCm39) I47F probably damaging Het
Thumpd1 A T 7: 119,317,471 (GRCm39) H143Q possibly damaging Het
Tmem231 T C 8: 112,640,697 (GRCm39) Q272R probably damaging Het
Tnfaip2 A G 12: 111,412,310 (GRCm39) D237G probably benign Het
Tox3 T C 8: 91,074,543 (GRCm39) D12G probably benign Het
Vmn1r1 A G 1: 181,985,309 (GRCm39) S119P probably damaging Het
Xrn1 A G 9: 95,870,999 (GRCm39) E608G probably benign Het
Zfp395 T C 14: 65,629,528 (GRCm39) C281R 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
R0138:Cyp46a1 UTSW 12 108,317,470 (GRCm39) missense probably damaging 1.00
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
R8992:Cyp46a1 UTSW 12 108,324,366 (GRCm39) missense possibly damaging 0.91
Predicted Primers PCR Primer
(F):5'- CCACACTATGGTCTGGCTAC -3'
(R):5'- TTCCCAAGCCAGCCATATAGGG -3'

Sequencing Primer
(F):5'- ACACTATGGTCTGGCTACATCCAC -3'
(R):5'- CAAATTTCCCTTCAGCTGGGTAAGG -3'
Posted On 2021-08-31