Mutagenetix > Incidental Mutation

Incidental Mutation 'R1572:Cyp46a1'

170885

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

039611-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R1572 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

108300640-108328493 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 108318198 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Lysine at position 203 (M203K)

Ref Sequence

ENSEMBL: ENSMUSP00000021684 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000021684] [ENSMUST00000221708]

AlphaFold

Q9WVK8

Predicted Effect

probably null
Transcript: ENSMUST00000021684
AA Change: M203K

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000021684
Gene: ENSMUSG00000021259
AA Change: M203K

Domain	Start	End	E-Value	Type
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

0.1286

Coding Region Coverage

1x: 98.7%
3x: 97.5%
10x: 92.9%
20x: 80.7%

Validation Efficiency

97% (130/134)

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: 112 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310030G06Rik	G	A	9: 50,651,973 (GRCm39)	T85M	probably damaging	Het
Actn1	A	G	12: 80,219,731 (GRCm39)		probably benign	Het
Afap1l1	A	T	18: 61,870,570 (GRCm39)	S603T	probably damaging	Het
Ahcy	T	C	2: 154,910,851 (GRCm39)	Y39C	probably benign	Het
Ankmy2	T	C	12: 36,236,941 (GRCm39)		probably null	Het
Anxa13	A	T	15: 58,220,655 (GRCm39)		noncoding transcript	Het
Aoc1	T	C	6: 48,882,720 (GRCm39)	S221P	possibly damaging	Het
Arhgef10	C	A	8: 15,041,211 (GRCm39)	A770D	possibly damaging	Het
Arhgef19	A	G	4: 140,982,065 (GRCm39)	D707G	probably benign	Het
Arhgef3	G	A	14: 27,123,692 (GRCm39)	R444H	probably damaging	Het
Asphd1	T	C	7: 126,548,271 (GRCm39)	I11V	probably benign	Het
Atp2b1	A	G	10: 98,830,537 (GRCm39)	M333V	probably benign	Het
BC051665	T	C	13: 60,932,841 (GRCm39)	Y40C	probably damaging	Het
Ccdc87	T	A	19: 4,890,341 (GRCm39)	S278T	probably benign	Het
Ccn3	T	A	15: 54,612,648 (GRCm39)	M219K	possibly damaging	Het
Cdcp3	T	A	7: 130,846,560 (GRCm39)	Y777*	probably null	Het
Chaf1b	G	A	16: 93,698,118 (GRCm39)	G463D	possibly damaging	Het
Chrna4	T	C	2: 180,671,100 (GRCm39)	T219A	possibly damaging	Het
Clcnkb	T	G	4: 141,134,406 (GRCm39)	T584P	possibly damaging	Het
Clptm1l	T	C	13: 73,755,866 (GRCm39)	S161P	probably benign	Het
Cmya5	T	C	13: 93,230,777 (GRCm39)	E1437G	possibly damaging	Het
Col13a1	A	T	10: 61,702,205 (GRCm39)		probably null	Het
Col3a1	T	C	1: 45,385,128 (GRCm39)	S82P	possibly damaging	Het
Cpeb3	A	T	19: 37,116,482 (GRCm39)	M383K	probably benign	Het
Cr2	T	A	1: 194,845,622 (GRCm39)	H111L	probably damaging	Het
Cttnbp2	T	C	6: 18,375,974 (GRCm39)	S1522G	possibly damaging	Het
Cul3	T	C	1: 80,260,506 (GRCm39)	D281G	possibly damaging	Het
Cyp2c70	T	G	19: 40,172,426 (GRCm39)	K72T	probably benign	Het
Cyp39a1	A	T	17: 43,991,020 (GRCm39)	I110F	probably damaging	Het
Cyp8b1	A	T	9: 121,744,024 (GRCm39)	V436D	possibly damaging	Het
Ddx17	T	C	15: 79,422,766 (GRCm39)	D324G	probably damaging	Het
Dop1b	A	G	16: 93,567,041 (GRCm39)	N1274S	probably damaging	Het
Dscaml1	G	A	9: 45,632,631 (GRCm39)	V1166I	probably benign	Het
Dsp	T	C	13: 38,379,714 (GRCm39)	V1554A	probably damaging	Het
Efr3a	T	A	15: 65,726,641 (GRCm39)		probably null	Het
Egfem1	A	T	3: 29,702,420 (GRCm39)	N223I	probably benign	Het
Egr2	T	C	10: 67,375,805 (GRCm39)	S147P	probably damaging	Het
Elmo3	A	G	8: 106,034,933 (GRCm39)	T408A	probably benign	Het
Flnb	A	G	14: 7,883,908 (GRCm38)	D378G	probably damaging	Het
Foxj2	T	A	6: 122,810,220 (GRCm39)	M193K	probably benign	Het
Gm6327	A	G	16: 12,578,020 (GRCm39)		noncoding transcript	Het
Gm7694	T	C	1: 170,130,335 (GRCm39)	H21R	probably benign	Het
Gpr107	A	G	2: 31,057,037 (GRCm39)	D43G	probably damaging	Het
Grid2	T	A	6: 64,406,678 (GRCm39)	Y679*	probably null	Het
Grin2c	G	A	11: 115,146,900 (GRCm39)	P432S	possibly damaging	Het
H2-M10.1	A	G	17: 36,636,625 (GRCm39)	F60L	possibly damaging	Het
Hectd4	A	G	5: 121,439,941 (GRCm39)	D1147G	possibly damaging	Het
Idua	G	T	5: 108,828,455 (GRCm39)	A223S	probably benign	Het
Ifi206	T	C	1: 173,314,419 (GRCm39)	Q7R	probably benign	Het
Itgad	T	A	7: 127,802,406 (GRCm39)	V986E	probably damaging	Het
Itsn2	G	A	12: 4,700,044 (GRCm39)	R670H	probably benign	Het
Kdm4a	T	C	4: 117,996,146 (GRCm39)	E961G	possibly damaging	Het
Klra5	T	A	6: 129,883,585 (GRCm39)	I91L	probably damaging	Het
Kntc1	A	G	5: 123,910,176 (GRCm39)	T525A	probably damaging	Het
Lct	A	G	1: 128,221,932 (GRCm39)	F1536L	probably benign	Het
Lmod1	T	A	1: 135,291,671 (GRCm39)	D175E	probably benign	Het
Lonrf1	A	C	8: 36,701,126 (GRCm39)	D361E	probably benign	Het
Lrrc19	T	C	4: 94,526,666 (GRCm39)	Y297C	probably damaging	Het
Mast4	T	C	13: 102,873,431 (GRCm39)	E1787G	possibly damaging	Het
Mpp2	G	A	11: 101,951,374 (GRCm39)	A452V	probably benign	Het
Msh2	T	C	17: 88,026,080 (GRCm39)	V686A	possibly damaging	Het
Mthfd1	C	T	12: 76,317,193 (GRCm39)	Q15*	probably null	Het
Mtnr1b	A	T	9: 15,774,438 (GRCm39)	I207N	probably damaging	Het
Nid2	A	G	14: 19,855,480 (GRCm39)	T1207A	probably benign	Het
Nin	A	T	12: 70,085,524 (GRCm39)	V1569D	probably damaging	Het
Nrcam	T	A	12: 44,584,147 (GRCm39)		probably benign	Het
Nsd1	T	A	13: 55,394,782 (GRCm39)	H897Q	probably damaging	Het
Or10g9	A	G	9: 39,912,490 (GRCm39)	F11S	probably benign	Het
Or12d2	A	T	17: 37,624,371 (GRCm39)	N301K	probably benign	Het
Or2w2	T	A	13: 21,758,480 (GRCm39)	I49F	possibly damaging	Het
Or7d10	G	T	9: 19,832,208 (GRCm39)	K234N	probably benign	Het
Paip1	T	C	13: 119,588,320 (GRCm39)		probably benign	Het
Pcnx3	G	A	19: 5,735,375 (GRCm39)	R484*	probably null	Het
Pdxk	A	G	10: 78,283,814 (GRCm39)	Y127H	probably damaging	Het
Phf20	T	A	2: 156,129,754 (GRCm39)	V442E	probably benign	Het
Phlpp1	G	A	1: 106,320,519 (GRCm39)	D1505N	probably damaging	Het
Pkhd1	T	C	1: 20,417,664 (GRCm39)	T2496A	probably benign	Het
Pkhd1l1	A	G	15: 44,406,869 (GRCm39)	T2369A	probably benign	Het
Plod2	T	A	9: 92,485,120 (GRCm39)		probably benign	Het
Pnpla7	T	A	2: 24,905,263 (GRCm39)	M617K	possibly damaging	Het
Ppp1r16a	C	T	15: 76,577,869 (GRCm39)	Q328*	probably null	Het
Prkch	T	A	12: 73,696,131 (GRCm39)		probably null	Het
Prr12	G	A	7: 44,678,224 (GRCm39)	H1974Y	unknown	Het
Prr16	A	G	18: 51,436,042 (GRCm39)	I174V	probably benign	Het
Prss45	A	T	9: 110,667,497 (GRCm39)	T39S	probably benign	Het
Pum1	T	A	4: 130,445,515 (GRCm39)	D161E	probably damaging	Het
Rad51ap2	A	G	12: 11,507,113 (GRCm39)	D345G	probably damaging	Het
Ralgapb	A	G	2: 158,288,119 (GRCm39)		probably benign	Het
Rasgrp3	A	G	17: 75,807,729 (GRCm39)	H262R	possibly damaging	Het
Rnf213	T	A	11: 119,327,437 (GRCm39)	I1809N	probably damaging	Het
Ryr1	A	G	7: 28,761,616 (GRCm39)	L3177P	probably damaging	Het
Scyl2	C	A	10: 89,486,818 (GRCm39)	R230L	probably damaging	Het
Sfxn2	T	C	19: 46,570,915 (GRCm39)		probably benign	Het
Slc18b1	T	C	10: 23,674,639 (GRCm39)		probably benign	Het
Spata31d1d	T	C	13: 59,876,005 (GRCm39)	H510R	probably benign	Het
Stab1	A	T	14: 30,872,780 (GRCm39)	N1109K	probably damaging	Het
Styxl2	C	T	1: 165,927,024 (GRCm39)	V863M	possibly damaging	Het
Sult3a2	A	G	10: 33,657,973 (GRCm39)	S47P	probably damaging	Het
Tenm3	T	C	8: 48,682,028 (GRCm39)	N2518S	possibly damaging	Het
Tex21	G	T	12: 76,253,665 (GRCm39)	P416Q	probably benign	Het
Tex38	T	C	4: 115,637,503 (GRCm39)	N100S	probably benign	Het
Thsd4	A	C	9: 60,301,836 (GRCm39)		probably benign	Het
Ticrr	T	C	7: 79,331,572 (GRCm39)	V723A	probably damaging	Het
Tmprss15	A	G	16: 78,887,717 (GRCm39)	V30A	probably benign	Het
Uba3	A	G	6: 97,162,298 (GRCm39)		probably benign	Het
Ubr1	T	C	2: 120,765,800 (GRCm39)		probably benign	Het
Uchl4	A	T	9: 64,143,013 (GRCm39)	I165L	probably benign	Het
Vmn2r112	A	T	17: 22,822,125 (GRCm39)	T268S	possibly damaging	Het
Wfdc3	T	C	2: 164,586,114 (GRCm39)		probably benign	Het
Zfp282	T	A	6: 47,869,801 (GRCm39)	L282Q	probably damaging	Het
Zfp422	A	T	6: 116,603,745 (GRCm39)	C85S	probably damaging	Het
Zfp790	A	T	7: 29,527,564 (GRCm39)	Q83L	probably benign	Het

Other mutations in Cyp46a1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
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'- TTGGTAATGAGGTAGCACAAAGCCC -3'
(R):5'- TCATTCTGGACACACTGGCACAC -3'

Sequencing Primer
(F):5'- CAGCCAGTAGAGTCATGGAC -3'
(R):5'- CAAAACCCACTCTGAAAGAAGTC -3'

Posted On

2014-04-13