Incidental Mutation 'PIT4651001:Cyp46a1'
ID 556691
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
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # PIT4651001 (G1)
Quality Score 201.009
Status Not validated
Chromosome 12
Chromosomal Location 108300640-108328493 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 108319367 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Glycine at position 288 (D288G)
Ref Sequence ENSEMBL: ENSMUSP00000021684 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000021684] [ENSMUST00000221708]
AlphaFold Q9WVK8
Predicted Effect probably benign
Transcript: ENSMUST00000021684
AA Change: D288G

PolyPhen 2 Score 0.169 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000021684
Gene: ENSMUSG00000021259
AA Change: D288G

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
Coding Region Coverage
  • 1x: 93.1%
  • 3x: 90.7%
  • 10x: 84.4%
  • 20x: 70.4%
Validation Efficiency
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: 74 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2210408I21Rik A T 13: 77,408,014 (GRCm39) I428L probably benign Het
Aass T C 6: 23,118,750 (GRCm39) I131V probably benign Het
Alcam T A 16: 52,115,550 (GRCm39) K189N probably benign Het
Ankrd50 C A 3: 38,509,959 (GRCm39) E803* probably null Het
Ankrd53 A G 6: 83,742,715 (GRCm39) D236G probably damaging Het
Bard1 A G 1: 71,114,087 (GRCm39) V298A probably benign Het
Cacna1d C T 14: 29,900,602 (GRCm39) G361D probably damaging Het
Camkk1 A G 11: 72,916,647 (GRCm39) S82G probably benign Het
Ccr4 A T 9: 114,321,261 (GRCm39) V268E probably benign Het
Cdh6 G A 15: 13,044,805 (GRCm39) S439L possibly damaging Het
Ces1e G T 8: 93,941,711 (GRCm39) A254E probably benign Het
Cfap46 T C 7: 139,225,467 (GRCm39) T1078A Het
Dnah6 T C 6: 73,037,243 (GRCm39) N3333S probably benign Het
Dzip3 A G 16: 48,765,241 (GRCm39) V491A probably benign Het
Egr1 G T 18: 34,996,240 (GRCm39) E341* probably null Het
Enpp1 G A 10: 24,529,848 (GRCm39) P597S probably benign Het
Ercc3 A T 18: 32,373,365 (GRCm39) probably benign Het
Fbn1 T C 2: 125,205,909 (GRCm39) probably null Het
Fbxw11 T C 11: 32,661,999 (GRCm39) probably null Het
Fhip1a C T 3: 85,590,948 (GRCm39) A389T probably damaging Het
Gbf1 A G 19: 46,151,982 (GRCm39) N5S probably benign Het
Gbp4 T A 5: 105,266,289 (GRCm39) H584L probably benign Het
Gcgr G T 11: 120,428,968 (GRCm39) C402F probably damaging Het
Grm7 T A 6: 110,623,050 (GRCm39) N74K probably benign Het
H1f9 A G 11: 94,859,142 (GRCm39) S146G probably benign Het
Hoxa10 T G 6: 52,211,877 (GRCm39) N13T possibly damaging Het
Ice1 A T 13: 70,772,040 (GRCm39) probably null Het
Il22 C A 10: 118,041,495 (GRCm39) N69K probably damaging Het
Il9r A T 11: 32,141,798 (GRCm39) H319Q probably benign Het
Itgax A G 7: 127,748,282 (GRCm39) T1104A probably benign Het
Jag1 C T 2: 136,943,617 (GRCm39) G193D probably damaging Het
Krt13 T A 11: 100,010,862 (GRCm39) D164V probably damaging Het
Lepr T C 4: 101,649,194 (GRCm39) M865T probably damaging Het
Lmf2 G A 15: 89,236,272 (GRCm39) H576Y possibly damaging Het
Lrrc8c C T 5: 105,756,189 (GRCm39) H655Y probably benign Het
Mapk6 A T 9: 75,304,869 (GRCm39) S183T possibly damaging Het
Mcrs1 A T 15: 99,144,832 (GRCm39) Y261N probably damaging Het
Mon1b G A 8: 114,365,254 (GRCm39) G194D probably benign Het
Myo18b C T 5: 112,982,301 (GRCm39) R1144Q probably benign Het
Myo9b T A 8: 71,795,456 (GRCm39) H808Q possibly damaging Het
Ngdn T C 14: 55,253,657 (GRCm39) I15T probably benign Het
Nhsl1 T G 10: 18,284,183 (GRCm39) S41R probably damaging Het
Numa1 A T 7: 101,663,141 (GRCm39) K2089M probably damaging Het
Obi1 T A 14: 104,743,692 (GRCm39) D129V probably damaging Het
Obscn A G 11: 58,932,507 (GRCm39) L4900P probably damaging Het
Olfm4 T A 14: 80,258,925 (GRCm39) L391Q probably benign Het
Or10g9b A T 9: 39,917,526 (GRCm39) C240S probably damaging Het
Or2ag1 A G 7: 106,472,730 (GRCm39) C241R probably damaging Het
Or5b106 T A 19: 13,123,991 (GRCm39) I11F probably benign Het
Or5b111 A G 19: 13,291,556 (GRCm39) I31T probably benign Het
Or5m9 T C 2: 85,876,862 (GRCm39) L12P probably damaging Het
Parn T A 16: 13,449,431 (GRCm39) N302Y probably benign Het
Pi4k2b T G 5: 52,905,812 (GRCm39) S118A possibly damaging Het
Piwil4 C T 9: 14,620,195 (GRCm39) V704I possibly damaging Het
Pm20d2 G A 4: 33,181,715 (GRCm39) T296M probably damaging Het
Pmpcb C T 5: 21,951,048 (GRCm39) A270V probably benign Het
Pnpt1 T C 11: 29,106,945 (GRCm39) probably null Het
Prkn T A 17: 11,286,130 (GRCm39) L41Q probably damaging Het
Rc3h1 C A 1: 160,791,110 (GRCm39) N931K probably benign Het
Rlf A G 4: 121,007,510 (GRCm39) V600A probably damaging Het
Rpl27rt A T 18: 34,870,892 (GRCm39) Q142L unknown Het
Sall1 T G 8: 89,757,731 (GRCm39) Q791P probably damaging Het
Sema3c T A 5: 17,899,731 (GRCm39) Y408N probably benign Het
Serpinb13 C T 1: 106,910,574 (GRCm39) S66L probably damaging Het
Tmem181a A T 17: 6,351,170 (GRCm39) M319L probably benign Het
Trim24 T C 6: 37,877,667 (GRCm39) probably null Het
Ttn T A 2: 76,719,278 (GRCm39) T7234S unknown Het
Unc13c T A 9: 73,391,021 (GRCm39) M2076L possibly damaging Het
Uroc1 C T 6: 90,340,095 (GRCm39) R667* probably null Het
Uvrag A G 7: 98,555,727 (GRCm39) F456L probably benign Het
Vmn1r215 T C 13: 23,260,530 (GRCm39) V190A probably damaging Het
Vmn2r50 T A 7: 9,771,659 (GRCm39) T681S probably benign Het
Vmn2r65 T A 7: 84,595,461 (GRCm39) T408S probably benign Het
Vps33b A G 7: 79,939,755 (GRCm39) D502G 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
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
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'- TGACATCCTCACGCAGATCCTC -3'
(R):5'- AACCACTTGCGAGGTCACAAG -3'

Sequencing Primer
(F):5'- TCACGCAGATCCTCAAAGGTG -3'
(R):5'- GGACAGCAAGAAGTCAGGCTC -3'
Posted On 2019-06-07