Mutagenetix > Incidental Mutation

Incidental Mutation 'R1466:Srebf1'

166076

Institutional Source

Beutler Lab

Gene Symbol

Srebf1

Ensembl Gene

ENSMUSG00000020538

Gene Name

sterol regulatory element binding transcription factor 1

Synonyms

SREBP-1a, SREBP-1c, ADD-1, SREBP1c, SREBP-1, bHLHd1, SREBP1

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1466 (G1)

Quality Score

186

Status

Not validated

Chromosome

Chromosomal Location

60199089-60222581 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 60200702 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Histidine at position 999 (R999H)

Ref Sequence

ENSEMBL: ENSMUSP00000020846 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000020846] [ENSMUST00000064190] [ENSMUST00000102688] [ENSMUST00000144942] [ENSMUST00000171108]

AlphaFold

Q9WTN3

Predicted Effect

probably benign
Transcript: ENSMUST00000020846
AA Change: R999H

PolyPhen 2 Score 0.012 (Sensitivity: 0.96; Specificity: 0.78)

SMART Domains

Protein: ENSMUSP00000020846
Gene: ENSMUSG00000020538
AA Change: R999H

Domain	Start	End	E-Value	Type
low complexity region	70	85	N/A	INTRINSIC
low complexity region	92	105	N/A	INTRINSIC
low complexity region	180	198	N/A	INTRINSIC
low complexity region	203	217	N/A	INTRINSIC
low complexity region	225	235	N/A	INTRINSIC
HLH	323	373	6.71e-16	SMART
low complexity region	420	453	N/A	INTRINSIC
transmembrane domain	480	502	N/A	INTRINSIC
transmembrane domain	533	555	N/A	INTRINSIC
low complexity region	589	601	N/A	INTRINSIC
low complexity region	650	661	N/A	INTRINSIC
low complexity region	679	692	N/A	INTRINSIC
low complexity region	1113	1125	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000064190

SMART Domains

Protein: ENSMUSP00000070896
Gene: ENSMUSG00000062115

Domain	Start	End	E-Value	Type
low complexity region	55	69	N/A	INTRINSIC
low complexity region	115	129	N/A	INTRINSIC
low complexity region	168	175	N/A	INTRINSIC
low complexity region	294	304	N/A	INTRINSIC
low complexity region	322	336	N/A	INTRINSIC
low complexity region	409	424	N/A	INTRINSIC
low complexity region	699	708	N/A	INTRINSIC
low complexity region	836	842	N/A	INTRINSIC
low complexity region	1015	1030	N/A	INTRINSIC
low complexity region	1049	1064	N/A	INTRINSIC
low complexity region	1084	1102	N/A	INTRINSIC
low complexity region	1262	1272	N/A	INTRINSIC
low complexity region	1375	1388	N/A	INTRINSIC
low complexity region	1455	1465	N/A	INTRINSIC
low complexity region	1499	1515	N/A	INTRINSIC
low complexity region	1597	1609	N/A	INTRINSIC
low complexity region	1680	1690	N/A	INTRINSIC
low complexity region	1714	1732	N/A	INTRINSIC
PHD	1838	1885	3.59e-6	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000102688

SMART Domains

Protein: ENSMUSP00000099749
Gene: ENSMUSG00000062115

Domain	Start	End	E-Value	Type
low complexity region	55	69	N/A	INTRINSIC
low complexity region	115	129	N/A	INTRINSIC
low complexity region	168	175	N/A	INTRINSIC
low complexity region	294	304	N/A	INTRINSIC
low complexity region	322	336	N/A	INTRINSIC
low complexity region	409	424	N/A	INTRINSIC
low complexity region	699	708	N/A	INTRINSIC
low complexity region	836	842	N/A	INTRINSIC
low complexity region	1015	1030	N/A	INTRINSIC
low complexity region	1049	1064	N/A	INTRINSIC
low complexity region	1084	1102	N/A	INTRINSIC
low complexity region	1262	1272	N/A	INTRINSIC
low complexity region	1375	1388	N/A	INTRINSIC
low complexity region	1455	1465	N/A	INTRINSIC
low complexity region	1499	1515	N/A	INTRINSIC
low complexity region	1597	1609	N/A	INTRINSIC
low complexity region	1680	1690	N/A	INTRINSIC
low complexity region	1714	1732	N/A	INTRINSIC
PHD	1838	1885	3.59e-6	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000129869

Predicted Effect

unknown
Transcript: ENSMUST00000134660
AA Change: R940H

SMART Domains

Protein: ENSMUSP00000122934
Gene: ENSMUSG00000020538
AA Change: R940H

Domain	Start	End	E-Value	Type
low complexity region	17	32	N/A	INTRINSIC
low complexity region	39	52	N/A	INTRINSIC
low complexity region	127	145	N/A	INTRINSIC
low complexity region	150	164	N/A	INTRINSIC
low complexity region	172	182	N/A	INTRINSIC
HLH	265	315	6.71e-16	SMART
low complexity region	362	395	N/A	INTRINSIC
transmembrane domain	422	444	N/A	INTRINSIC
transmembrane domain	475	497	N/A	INTRINSIC
low complexity region	531	543	N/A	INTRINSIC
low complexity region	592	603	N/A	INTRINSIC
low complexity region	621	634	N/A	INTRINSIC
low complexity region	1055	1067	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000136426

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000141161

Predicted Effect

probably benign
Transcript: ENSMUST00000144942
AA Change: R975H

PolyPhen 2 Score 0.004 (Sensitivity: 0.98; Specificity: 0.59)

SMART Domains

Protein: ENSMUSP00000120777
Gene: ENSMUSG00000020538
AA Change: R975H

Domain	Start	End	E-Value	Type
low complexity region	46	61	N/A	INTRINSIC
low complexity region	68	81	N/A	INTRINSIC
low complexity region	156	174	N/A	INTRINSIC
low complexity region	179	193	N/A	INTRINSIC
low complexity region	201	211	N/A	INTRINSIC
HLH	299	349	6.71e-16	SMART
low complexity region	396	429	N/A	INTRINSIC
transmembrane domain	456	478	N/A	INTRINSIC
transmembrane domain	509	531	N/A	INTRINSIC
low complexity region	565	577	N/A	INTRINSIC
low complexity region	626	637	N/A	INTRINSIC
low complexity region	655	668	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000149238

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000149770

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000154620

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000154925

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000156304

Predicted Effect

probably benign
Transcript: ENSMUST00000171108

SMART Domains

Protein: ENSMUSP00000126183
Gene: ENSMUSG00000062115

Domain	Start	End	E-Value	Type
low complexity region	55	69	N/A	INTRINSIC
low complexity region	115	129	N/A	INTRINSIC
low complexity region	168	175	N/A	INTRINSIC
low complexity region	294	304	N/A	INTRINSIC
low complexity region	322	336	N/A	INTRINSIC
low complexity region	409	424	N/A	INTRINSIC
low complexity region	699	708	N/A	INTRINSIC
low complexity region	836	842	N/A	INTRINSIC
low complexity region	1015	1030	N/A	INTRINSIC
low complexity region	1049	1064	N/A	INTRINSIC
low complexity region	1084	1102	N/A	INTRINSIC
low complexity region	1262	1272	N/A	INTRINSIC
low complexity region	1375	1388	N/A	INTRINSIC
low complexity region	1455	1465	N/A	INTRINSIC
low complexity region	1499	1515	N/A	INTRINSIC
low complexity region	1597	1609	N/A	INTRINSIC
low complexity region	1680	1690	N/A	INTRINSIC
low complexity region	1714	1732	N/A	INTRINSIC
PHD	1838	1885	3.59e-6	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000183719

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000185099

Meta Mutation Damage Score

0.0751

Coding Region Coverage

1x: 99.4%
3x: 97.9%
10x: 90.8%
20x: 71.5%

Validation Efficiency

MGI Phenotype

FUNCTION: This gene encodes a transcription factor that binds to the sterol regulatory element-1 (SRE1), which is a decamer flanking the low density lipoprotein receptor gene and some genes involved in sterol biosynthesis. The protein is synthesized as a precursor that is attached to the nuclear membrane and endoplasmic reticulum. Following cleavage, the mature protein translocates to the nucleus and activates transcription by binding to the SRE1. Sterols inhibit the cleavage of the precursor, and the mature nuclear form is rapidly catabolized, thereby reducing transcription. The protein is a member of the basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor family. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]
PHENOTYPE: Mice homozygous for a knock-out allele of transcript A die between E11.5 and E14.5. Mice homozygous for a knock-out allele of transcript C exhibit decreased circulating triglyceride levels. Mice homozygous for a gene trap allele exhibit decreased hepatictriglyceride storage. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 108 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abhd15	C	T	11: 77,515,410	A71V	probably damaging	Het
Adamts12	T	C	15: 11,311,359	F1234S	probably benign	Het
Ahnak	A	G	19: 9,015,875	D4841G	probably damaging	Het
Akap13	T	C	7: 75,729,049	S2095P	possibly damaging	Het
Ampd2	T	C	3: 108,080,337		probably null	Het
Arhgef17	G	T	7: 100,929,659	P694Q	possibly damaging	Het
Arrdc1	T	C	2: 24,925,795	I398V	probably benign	Het
Ash1l	T	C	3: 89,052,065	Y2250H	probably damaging	Het
Aspg	A	G	12: 112,121,852	N385D	probably benign	Het
Atxn3	G	A	12: 101,926,499	R319C	possibly damaging	Het
BC005561	T	A	5: 104,518,257	I215N	probably damaging	Het
Brca2	G	A	5: 150,552,258	A2478T	probably damaging	Het
C1s1	C	T	6: 124,531,131	C633Y	probably damaging	Het
C8g	C	T	2: 25,500,216	A6T	probably benign	Het
Cbl	A	T	9: 44,154,244	V706E	probably benign	Het
Cfhr1	C	T	1: 139,557,574	E45K	probably benign	Het
Chd7	G	A	4: 8,840,561		probably null	Het
Chek1	G	T	9: 36,725,857	A2E	probably damaging	Het
Cntnap1	C	A	11: 101,180,360	F366L	probably damaging	Het
Corin	C	T	5: 72,302,790		probably null	Het
Crb2	T	C	2: 37,783,388	Y99H	probably damaging	Het
Ctdspl2	G	A	2: 122,003,929	R332K	probably benign	Het
Cym	G	A	3: 107,213,458	T277I	probably damaging	Het
Cyp2d11	C	T	15: 82,391,735	C215Y	probably benign	Het
Dido1	G	A	2: 180,662,328	P1261L	probably damaging	Het
Dnah10	T	A	5: 124,763,096	Y1265N	probably benign	Het
Dtx3l	G	A	16: 35,932,728	L503F	probably damaging	Het
Efhb	A	G	17: 53,437,178	F462L	probably damaging	Het
Enpep	T	A	3: 129,319,448	T203S	probably damaging	Het
Fat3	A	C	9: 16,375,482	V915G	probably damaging	Het
Fbln7	A	G	2: 128,877,429	T49A	probably benign	Het
Fcho1	C	T	8: 71,712,560	A418T	probably benign	Het
Fgf14	T	A	14: 124,676,539	K60M	probably benign	Het
Galnt4	A	G	10: 99,108,709	R99G	probably benign	Het
Gimap4	C	A	6: 48,691,282	Q196K	probably benign	Het
Glcci1	C	T	6: 8,537,964	T6I	probably damaging	Het
Gm10110	A	T	14: 89,898,075		noncoding transcript	Het
Gm4884	A	G	7: 41,043,128	K174E	probably damaging	Het
Gm6583	C	T	5: 112,354,764	G358D	probably benign	Het
Grip2	A	T	6: 91,788,443	D19E	probably damaging	Het
Grk4	T	C	5: 34,694,750	S113P	probably benign	Het
Hectd3	G	A	4: 116,996,566	E220K	probably damaging	Het
Helz2	G	A	2: 181,236,297	P903S	probably damaging	Het
Hydin	T	A	8: 110,532,953	V2519E	possibly damaging	Het
Ints11	G	A	4: 155,888,110		probably null	Het
Kif1a	A	G	1: 93,054,929	W718R	possibly damaging	Het
Kif1b	A	T	4: 149,223,252	Y839N	probably damaging	Het
Kif20b	T	A	19: 34,950,599	V1047D	probably benign	Het
Klhl23	T	C	2: 69,833,888	I527T	probably damaging	Het
Klra10	T	A	6: 130,279,315	R125S	probably damaging	Het
Klra10	T	C	6: 130,279,431	N87D	probably damaging	Het
Lars	G	A	18: 42,210,050	R1101C	probably damaging	Het
Lcn4	G	A	2: 26,668,576	P166L	probably damaging	Het
Letmd1	T	A	15: 100,472,542		probably null	Het
Map4k2	G	T	19: 6,341,917	W87L	probably damaging	Het
Mccc1	A	G	3: 35,974,286	V457A	probably benign	Het
Mdn1	T	A	4: 32,730,788	S2886T	probably benign	Het
Mroh2b	G	T	15: 4,925,684	D720Y	probably damaging	Het
Mrpl24	T	A	3: 87,921,928	Y21*	probably null	Het
Mrps35	C	T	6: 147,055,984	T169M	probably damaging	Het
Mtcl1	T	A	17: 66,380,435	D492V	probably damaging	Het
Muc2	A	G	7: 141,748,974	Y457C	probably damaging	Het
Muc4	G	A	16: 32,753,595	G1157D	probably benign	Het
Myg1	T	A	15: 102,337,390	L275Q	probably damaging	Het
Naga	T	A	15: 82,334,788	M237L	probably null	Het
Oc90	T	A	15: 65,897,720	Y96F	probably damaging	Het
Olfr1029	T	A	2: 85,975,995	F251I	probably damaging	Het
Olfr103	A	T	17: 37,336,956	L92H	probably benign	Het
Olfr1253	C	T	2: 89,752,267	C187Y	probably damaging	Het
Olfr46	A	G	7: 140,610,969	I268V	probably benign	Het
Olfr522	A	G	7: 140,162,203	V249A	probably damaging	Het
Orc4	A	T	2: 48,909,494	C324S	possibly damaging	Het
Pcdh10	T	G	3: 45,379,974	L241R	probably damaging	Het
Pdzrn4	T	C	15: 92,770,537	S857P	probably benign	Het
Plec	C	T	15: 76,185,908	E1000K	possibly damaging	Het
Plvap	A	T	8: 71,508,481	V149D	probably benign	Het
Ppef1	C	A	X: 160,625,674		probably null	Het
Prkaa1	C	A	15: 5,178,798	P507T	probably benign	Het
Ptch1	A	G	13: 63,524,969	Y804H	probably benign	Het
R3hdm2	A	G	10: 127,476,690	I434V	probably benign	Het
Rfx5	T	A	3: 94,956,303	Y88N	probably damaging	Het
Rnase2b	A	T	14: 51,162,839	K126*	probably null	Het
Rpl3l	A	G	17: 24,730,871	I15V	probably benign	Het
Saal1	G	T	7: 46,702,545		probably null	Het
Sbpl	A	C	17: 23,953,254	D230E	unknown	Het
Scn10a	T	C	9: 119,666,490	Y322C	probably damaging	Het
Sec16a	A	T	2: 26,431,157	Y1308N	probably damaging	Het
Sis	A	T	3: 72,932,060	D824E	possibly damaging	Het
Slc25a36	A	G	9: 97,080,355	F194L	probably damaging	Het
Slc27a4	T	A	2: 29,811,190	V331E	probably damaging	Het
Slc7a11	G	T	3: 50,381,073		probably null	Het
Slco4c1	A	T	1: 96,841,172	S322T	probably damaging	Het
Smarcc2	A	T	10: 128,474,245	T376S	probably damaging	Het
St3gal3	A	C	4: 118,107,662	M1R	probably null	Het
Syp	A	T	X: 7,648,705		probably benign	Het
Tas1r2	A	G	4: 139,669,411	D687G	probably damaging	Het
Tekt4	A	T	17: 25,472,074	Q118L	probably benign	Het
Tph2	T	C	10: 115,079,695	N480S	probably benign	Het
Tsc2	A	T	17: 24,608,973	M839K	probably damaging	Het
Ttc22	T	C	4: 106,622,780	F77S	probably damaging	Het
Uaca	C	T	9: 60,854,321	A205V	possibly damaging	Het
Uhmk1	A	T	1: 170,208,653		probably null	Het
Usp17lc	A	G	7: 103,418,941	H481R	possibly damaging	Het
Vwa3a	A	G	7: 120,768,165	Y181C	probably damaging	Het
Wfikkn2	G	A	11: 94,238,895	T140I	probably damaging	Het
Zfp704	G	T	3: 9,447,348	T288N	possibly damaging	Het
Zfp93	T	C	7: 24,276,096	V502A	probably damaging	Het
Zzef1	C	T	11: 72,924,679	P2942S	probably damaging	Het

Other mutations in Srebf1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00770:Srebf1	APN	11	60205139	missense	probably damaging	0.96
IGL00774:Srebf1	APN	11	60205139	missense	probably damaging	0.96
IGL01824:Srebf1	APN	11	60204131	missense	probably benign	0.01
IGL02097:Srebf1	APN	11	60202824	missense	probably damaging	1.00
IGL02808:Srebf1	APN	11	60201713	critical splice acceptor site	probably null
IGL03036:Srebf1	APN	11	60220458	missense	possibly damaging	0.85
IGL03055:Srebf1	UTSW	11	60207076	synonymous	silent
R0109:Srebf1	UTSW	11	60201804	missense	probably benign	0.21
R0109:Srebf1	UTSW	11	60201804	missense	probably benign	0.21
R0550:Srebf1	UTSW	11	60201676	missense	probably benign	0.00
R0654:Srebf1	UTSW	11	60204116	missense	probably benign
R0707:Srebf1	UTSW	11	60204116	missense	probably benign
R1466:Srebf1	UTSW	11	60200702	missense	probably benign	0.01
R1584:Srebf1	UTSW	11	60200702	missense	probably benign	0.01
R1899:Srebf1	UTSW	11	60203486	missense	probably damaging	1.00
R1900:Srebf1	UTSW	11	60203486	missense	probably damaging	1.00
R1905:Srebf1	UTSW	11	60204493	missense	probably damaging	1.00
R2172:Srebf1	UTSW	11	60206502	missense	probably benign
R2191:Srebf1	UTSW	11	60220539	missense	probably damaging	1.00
R2267:Srebf1	UTSW	11	60207147	missense	probably damaging	0.99
R2268:Srebf1	UTSW	11	60207147	missense	probably damaging	0.99
R5511:Srebf1	UTSW	11	60210358	utr 5 prime	probably benign
R5841:Srebf1	UTSW	11	60203584	missense	possibly damaging	0.65
R5870:Srebf1	UTSW	11	60203584	missense	possibly damaging	0.65
R6003:Srebf1	UTSW	11	60207104	missense	possibly damaging	0.82
R6371:Srebf1	UTSW	11	60203515	missense	probably damaging	1.00
R6376:Srebf1	UTSW	11	60203535	missense	probably null	0.19
R7009:Srebf1	UTSW	11	60200526	missense	probably damaging	1.00
R7029:Srebf1	UTSW	11	60206984	missense	probably damaging	1.00
R7410:Srebf1	UTSW	11	60205867	missense	probably benign	0.03
R7569:Srebf1	UTSW	11	60200121	missense	possibly damaging	0.69
R8317:Srebf1	UTSW	11	60200657	missense	possibly damaging	0.62
R8370:Srebf1	UTSW	11	60202196	missense	probably benign
R8871:Srebf1	UTSW	11	60200769	missense	probably benign
R9433:Srebf1	UTSW	11	60204189	missense	possibly damaging	0.63
R9582:Srebf1	UTSW	11	60207042	missense	probably benign	0.00
RF009:Srebf1	UTSW	11	60204116	missense	probably benign
X0017:Srebf1	UTSW	11	60202881	missense	probably damaging	0.96
X0025:Srebf1	UTSW	11	60203427	missense	probably benign	0.00
Z1176:Srebf1	UTSW	11	60207156	missense	possibly damaging	0.95
Z1186:Srebf1	UTSW	11	60206235	missense	probably benign	0.03
Z1187:Srebf1	UTSW	11	60206235	missense	probably benign	0.03
Z1188:Srebf1	UTSW	11	60206235	missense	probably benign	0.03
Z1189:Srebf1	UTSW	11	60206235	missense	probably benign	0.03
Z1190:Srebf1	UTSW	11	60206235	missense	probably benign	0.03
Z1191:Srebf1	UTSW	11	60206235	missense	probably benign	0.03
Z1192:Srebf1	UTSW	11	60206235	missense	probably benign	0.03

Predicted Primers

PCR Primer
(F):5'- GCAAGGAGTAGTCACCCGTTTCAG -3'
(R):5'- GCAGTGCTTCAGTGATGCAACC -3'

Sequencing Primer
(F):5'- GAGTAGTCACCCGTTTCAGATTTAC -3'
(R):5'- GCTTGATGTCCATAGGGAAACTC -3'

Posted On

2014-03-28