Mutagenetix > Incidental Mutation

Incidental Mutation 'R7009:Srebf1'

544916

Institutional Source

Beutler Lab

Gene Symbol

Srebf1

Ensembl Gene

ENSMUSG00000020538

Gene Name

sterol regulatory element binding transcription factor 1

Synonyms

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

MMRRC Submission

045111-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7009 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

60089915-60113407 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to C at 60091352 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Glutamine at position 1025 (H1025Q)

Ref Sequence

ENSEMBL: ENSMUSP00000020846 (fasta)

Gene Model

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

AlphaFold

Q9WTN3

Predicted Effect

probably damaging
Transcript: ENSMUST00000020846
AA Change: H1025Q

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000020846
Gene: ENSMUSG00000020538
AA Change: H1025Q

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

SMART Domains

Protein: ENSMUSP00000122934
Gene: ENSMUSG00000020538
AA Change: H966Q

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

probably damaging
Transcript: ENSMUST00000144942
AA Change: H1001Q

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000120777
Gene: ENSMUSG00000020538
AA Change: H1001Q

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

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

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.2%

Validation Efficiency

99% (82/83)

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: 83 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4921517D22Rik	G	T	13: 59,838,624 (GRCm39)	D69E	possibly damaging	Het
Abat	A	C	16: 8,420,231 (GRCm39)	M177L	probably benign	Het
Acadvl	A	G	11: 69,905,617 (GRCm39)		probably null	Het
Adam5	T	C	8: 25,296,454 (GRCm39)	N331S	probably benign	Het
Ager	A	G	17: 34,819,710 (GRCm39)	E372G	probably damaging	Het
Angpt1	T	A	15: 42,386,991 (GRCm39)	Q121L	possibly damaging	Het
Apoa4	A	T	9: 46,154,178 (GRCm39)	I260F	possibly damaging	Het
Arhgap32	A	T	9: 32,157,272 (GRCm39)	I90F	probably damaging	Het
Arhgap5	A	T	12: 52,566,422 (GRCm39)	Q1131L	probably benign	Het
Bach1	G	A	16: 87,516,179 (GRCm39)	R240Q	probably benign	Het
Cacna2d3	A	T	14: 28,691,322 (GRCm39)	M1K	probably null	Het
Ccdc18	G	A	5: 108,321,728 (GRCm39)		probably null	Het
Ccdc42	T	C	11: 68,485,442 (GRCm39)	F267S	probably damaging	Het
Cdh23	T	A	10: 60,173,085 (GRCm39)	Y1700F	probably damaging	Het
Cenpe	A	T	3: 134,940,962 (GRCm39)	S704C	probably damaging	Het
Cenpe	G	A	3: 134,940,963 (GRCm39)	S704N	probably benign	Het
Cfap299	A	T	5: 98,932,379 (GRCm39)	D193V	probably damaging	Het
Cfap54	A	T	10: 92,710,881 (GRCm39)	S2727T	unknown	Het
Clu	T	A	14: 66,209,281 (GRCm39)	V113D	probably damaging	Het
Cnbd2	A	G	2: 156,161,954 (GRCm39)	I98V	probably benign	Het
Copa	G	T	1: 171,918,567 (GRCm39)	R97L	probably damaging	Het
Epb41l1	C	A	2: 156,376,603 (GRCm39)		probably null	Het
Etnk1	T	A	6: 143,148,880 (GRCm39)		probably null	Het
Fnip1	A	T	11: 54,393,761 (GRCm39)	K732N	probably damaging	Het
G6pd2	A	G	5: 61,966,234 (GRCm39)	E3G	probably benign	Het
Gal3st2	A	G	1: 93,801,481 (GRCm39)	T95A	probably benign	Het
Gapvd1	A	G	2: 34,590,829 (GRCm39)	S948P	probably damaging	Het
Ggps1	A	T	13: 14,228,750 (GRCm39)	Y8*	probably null	Het
Gria2	T	C	3: 80,614,279 (GRCm39)	E587G	probably damaging	Het
Hpse	T	C	5: 100,840,145 (GRCm39)	E324G	probably benign	Het
Il16	G	A	7: 83,295,596 (GRCm39)	T493I	probably benign	Het
Ints1	T	C	5: 139,754,217 (GRCm39)	T652A	possibly damaging	Het
Ism1	A	G	2: 139,599,199 (GRCm39)	I391V	probably damaging	Het
Katnb1	A	G	8: 95,825,012 (GRCm39)	D598G	probably damaging	Het
Kif5c	A	G	2: 49,647,441 (GRCm39)	S880G	probably benign	Het
Klra8	T	C	6: 130,102,147 (GRCm39)	N96S	probably benign	Het
Krt79	T	A	15: 101,839,876 (GRCm39)	D373V	probably damaging	Het
Lamtor4	G	A	5: 138,257,374 (GRCm39)	R92Q	probably benign	Het
Lce1d	C	A	3: 92,593,353 (GRCm39)	C20F	unknown	Het
Limk1	T	C	5: 134,701,553 (GRCm39)	T117A	probably benign	Het
Medag	A	T	5: 149,350,708 (GRCm39)	K61M	probably benign	Het
Mkrn3	T	C	7: 62,069,366 (GRCm39)	M142V	probably benign	Het
Mob3c	G	A	4: 115,688,779 (GRCm39)	R104H	probably benign	Het
Morc1	G	T	16: 48,447,433 (GRCm39)	R903L	possibly damaging	Het
Myh6	T	C	14: 55,189,749 (GRCm39)	E1099G	probably damaging	Het
Nphp3	T	G	9: 103,893,315 (GRCm39)	C434G	probably null	Het
Npr3	C	T	15: 11,905,334 (GRCm39)	C131Y	probably damaging	Het
Oacyl	C	A	18: 65,855,609 (GRCm39)	Y112*	probably null	Het
Oprl1	A	G	2: 181,360,174 (GRCm39)	T77A	probably damaging	Het
Osgep	A	G	14: 51,162,165 (GRCm39)	V24A	probably damaging	Het
Otx2	T	A	14: 48,896,254 (GRCm39)	K260M	probably damaging	Het
Pdcd11	T	C	19: 47,101,581 (GRCm39)	L922P	probably benign	Het
Pgap4	A	T	4: 49,586,325 (GRCm39)	M281K	probably benign	Het
Phldb1	A	G	9: 44,605,705 (GRCm39)	V375A	probably damaging	Het
Pip5k1b	C	T	19: 24,337,299 (GRCm39)		probably null	Het
Psmd3	G	A	11: 98,573,592 (GRCm39)	D13N	probably benign	Het
Ptprc	G	A	1: 137,992,291 (GRCm39)	H1140Y	probably damaging	Het
Ranbp3l	A	T	15: 9,063,064 (GRCm39)	H291L	probably damaging	Het
Rasa4	T	A	5: 136,130,217 (GRCm39)	D324E	probably damaging	Het
Rilpl1	T	A	5: 124,641,755 (GRCm39)		silent	Het
Rin2	A	C	2: 145,725,395 (GRCm39)	D794A	probably damaging	Het
Ripk1	A	G	13: 34,214,045 (GRCm39)	I522M	probably damaging	Het
Rnf31	T	C	14: 55,830,008 (GRCm39)	Y143H	probably benign	Het
Rp1	T	G	1: 4,112,291 (GRCm39)	I1187L	unknown	Het
Rps6ka5	G	A	12: 100,585,796 (GRCm39)	H166Y	probably damaging	Het
Rrm1	T	C	7: 102,109,541 (GRCm39)	V455A	probably damaging	Het
Runx2	G	A	17: 45,125,079 (GRCm39)	P80L	probably damaging	Het
Scn5a	T	G	9: 119,314,996 (GRCm39)	E1904A	probably damaging	Het
Sec16a	G	T	2: 26,326,014 (GRCm39)	S240*	probably null	Het
Slc22a8	C	T	19: 8,582,781 (GRCm39)	T154I	probably benign	Het
Slc25a16	T	A	10: 62,773,233 (GRCm39)	V156E	possibly damaging	Het
Slc28a3	A	T	13: 58,758,618 (GRCm39)	S2T	probably benign	Het
Srd5a3	G	A	5: 76,297,713 (GRCm39)	V48I	probably benign	Het
Stard9	A	G	2: 120,527,672 (GRCm39)	K1310E	probably benign	Het
Swt1	A	G	1: 151,246,381 (GRCm39)	V848A	possibly damaging	Het
Tanc2	A	T	11: 105,731,525 (GRCm39)	T434S	possibly damaging	Het
Tcf20	G	A	15: 82,738,883 (GRCm39)	T856I	probably benign	Het
Tcf7l2	T	C	19: 55,883,165 (GRCm39)		probably null	Het
Trim45	A	G	3: 100,839,195 (GRCm39)		probably benign	Het
Tsen2	T	A	6: 115,524,933 (GRCm39)	M44K	possibly damaging	Het
Ttc21a	T	A	9: 119,787,139 (GRCm39)	C715*	probably null	Het
Vmn2r102	G	A	17: 19,914,456 (GRCm39)	V674I	probably damaging	Het
Zfp87	A	G	13: 67,665,173 (GRCm39)	S430P	probably damaging	Het

Other mutations in Srebf1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00770:Srebf1	APN	11	60,095,965 (GRCm39)	missense	probably damaging	0.96
IGL00774:Srebf1	APN	11	60,095,965 (GRCm39)	missense	probably damaging	0.96
IGL01824:Srebf1	APN	11	60,094,957 (GRCm39)	missense	probably benign	0.01
IGL02097:Srebf1	APN	11	60,093,650 (GRCm39)	missense	probably damaging	1.00
IGL02808:Srebf1	APN	11	60,092,539 (GRCm39)	critical splice acceptor site	probably null
IGL03036:Srebf1	APN	11	60,111,284 (GRCm39)	missense	possibly damaging	0.85
IGL03055:Srebf1	UTSW	11	60,097,902 (GRCm39)	synonymous	silent
R0109:Srebf1	UTSW	11	60,092,630 (GRCm39)	missense	probably benign	0.21
R0109:Srebf1	UTSW	11	60,092,630 (GRCm39)	missense	probably benign	0.21
R0550:Srebf1	UTSW	11	60,092,502 (GRCm39)	missense	probably benign	0.00
R0654:Srebf1	UTSW	11	60,094,942 (GRCm39)	missense	probably benign
R0707:Srebf1	UTSW	11	60,094,942 (GRCm39)	missense	probably benign
R1466:Srebf1	UTSW	11	60,091,528 (GRCm39)	missense	probably benign	0.01
R1466:Srebf1	UTSW	11	60,091,528 (GRCm39)	missense	probably benign	0.01
R1584:Srebf1	UTSW	11	60,091,528 (GRCm39)	missense	probably benign	0.01
R1899:Srebf1	UTSW	11	60,094,312 (GRCm39)	missense	probably damaging	1.00
R1900:Srebf1	UTSW	11	60,094,312 (GRCm39)	missense	probably damaging	1.00
R1905:Srebf1	UTSW	11	60,095,319 (GRCm39)	missense	probably damaging	1.00
R2172:Srebf1	UTSW	11	60,097,328 (GRCm39)	missense	probably benign
R2191:Srebf1	UTSW	11	60,111,365 (GRCm39)	missense	probably damaging	1.00
R2267:Srebf1	UTSW	11	60,097,973 (GRCm39)	missense	probably damaging	0.99
R2268:Srebf1	UTSW	11	60,097,973 (GRCm39)	missense	probably damaging	0.99
R5511:Srebf1	UTSW	11	60,101,184 (GRCm39)	utr 5 prime	probably benign
R5841:Srebf1	UTSW	11	60,094,410 (GRCm39)	missense	possibly damaging	0.65
R5870:Srebf1	UTSW	11	60,094,410 (GRCm39)	missense	possibly damaging	0.65
R6003:Srebf1	UTSW	11	60,097,930 (GRCm39)	missense	possibly damaging	0.82
R6371:Srebf1	UTSW	11	60,094,341 (GRCm39)	missense	probably damaging	1.00
R6376:Srebf1	UTSW	11	60,094,361 (GRCm39)	missense	probably null	0.19
R7029:Srebf1	UTSW	11	60,097,810 (GRCm39)	missense	probably damaging	1.00
R7410:Srebf1	UTSW	11	60,096,693 (GRCm39)	missense	probably benign	0.03
R7569:Srebf1	UTSW	11	60,090,947 (GRCm39)	missense	possibly damaging	0.69
R8317:Srebf1	UTSW	11	60,091,483 (GRCm39)	missense	possibly damaging	0.62
R8370:Srebf1	UTSW	11	60,093,022 (GRCm39)	missense	probably benign
R8871:Srebf1	UTSW	11	60,091,595 (GRCm39)	missense	probably benign
R9433:Srebf1	UTSW	11	60,095,015 (GRCm39)	missense	possibly damaging	0.63
R9582:Srebf1	UTSW	11	60,097,868 (GRCm39)	missense	probably benign	0.00
RF009:Srebf1	UTSW	11	60,094,942 (GRCm39)	missense	probably benign
X0017:Srebf1	UTSW	11	60,093,707 (GRCm39)	missense	probably damaging	0.96
X0025:Srebf1	UTSW	11	60,094,253 (GRCm39)	missense	probably benign	0.00
Z1176:Srebf1	UTSW	11	60,097,982 (GRCm39)	missense	possibly damaging	0.95
Z1186:Srebf1	UTSW	11	60,097,061 (GRCm39)	missense	probably benign	0.03
Z1187:Srebf1	UTSW	11	60,097,061 (GRCm39)	missense	probably benign	0.03
Z1188:Srebf1	UTSW	11	60,097,061 (GRCm39)	missense	probably benign	0.03
Z1189:Srebf1	UTSW	11	60,097,061 (GRCm39)	missense	probably benign	0.03
Z1190:Srebf1	UTSW	11	60,097,061 (GRCm39)	missense	probably benign	0.03
Z1191:Srebf1	UTSW	11	60,097,061 (GRCm39)	missense	probably benign	0.03
Z1192:Srebf1	UTSW	11	60,097,061 (GRCm39)	missense	probably benign	0.03

Predicted Primers

PCR Primer
(F):5'- AAGTCAGCTCTCAGTATGTCTC -3'
(R):5'- TCACGGTACCAGCAATGGAC -3'

Sequencing Primer
(F):5'- AGTCAGCTCTCAGTATGTCTCACTAG -3'
(R):5'- AGCTGCGTGGTTTCCAAC -3'

Posted On

2019-05-13