Mutagenetix > Incidental Mutation

Incidental Mutation 'R1899:Srebf1'

214117

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

MMRRC Submission

039919-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1899 (G1)

Quality Score

217

Status

Validated

Chromosome

Chromosomal Location

60199089-60222581 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 60203486 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Proline at position 601 (L601P)

Ref Sequence

ENSEMBL: ENSMUSP00000120777 (fasta)

Gene Model

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

AlphaFold

Q9WTN3

Predicted Effect

probably damaging
Transcript: ENSMUST00000020846
AA Change: L625P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000020846
Gene: ENSMUSG00000020538
AA Change: L625P

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

probably damaging
Transcript: ENSMUST00000134660
AA Change: L566P

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000122934
Gene: ENSMUSG00000020538
AA Change: L566P

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: ENSMUST00000136215

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000136426

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000141161

Predicted Effect

probably damaging
Transcript: ENSMUST00000144942
AA Change: L601P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000120777
Gene: ENSMUSG00000020538
AA Change: L601P

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: ENSMUST00000147967

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

noncoding transcript
Transcript: ENSMUST00000185099

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000183719

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

Meta Mutation Damage Score

0.9630

Coding Region Coverage

1x: 97.5%
3x: 97.0%
10x: 95.6%
20x: 93.4%

Validation Efficiency

94% (94/100)

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: 98 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
0610009O20Rik	T	C	18: 38,258,342	W378R	probably benign	Het
4930522L14Rik	T	A	5: 109,736,798	Q398L	probably benign	Het
4930596D02Rik	T	G	14: 35,810,132	K162T	probably damaging	Het
Abca8b	G	T	11: 109,937,918	T1353K	possibly damaging	Het
Abcg3	A	C	5: 104,938,199	C565G	probably damaging	Het
Actr3b	G	A	5: 25,829,538	V185I	possibly damaging	Het
Akap6	A	T	12: 53,141,852	E2016D	possibly damaging	Het
Aldh3b2	T	C	19: 3,978,662	V148A	possibly damaging	Het
Ankfy1	C	T	11: 72,754,407	Q771*	probably null	Het
Anks1b	A	G	10: 90,260,756	D425G	probably damaging	Het
Arrb1	T	C	7: 99,582,297		probably benign	Het
Atg2a	C	A	19: 6,245,067	T170N	probably damaging	Het
Atp8b5	C	T	4: 43,361,804	R617C	possibly damaging	Het
Bicra	T	C	7: 15,987,751	T614A	possibly damaging	Het
Cacna1i	A	G	15: 80,391,642	D167G	possibly damaging	Het
Calr4	T	G	4: 109,246,293		probably null	Het
Camsap3	G	T	8: 3,603,922	E515*	probably null	Het
Casp8ap2	T	C	4: 32,643,647	S907P	probably damaging	Het
Cdk19	T	A	10: 40,479,780		probably benign	Het
Chst14	A	G	2: 118,927,015	M122V	possibly damaging	Het
Cntn4	A	G	6: 106,675,813	M748V	probably benign	Het
Col7a1	A	G	9: 108,978,888	D2552G	unknown	Het
Cpeb2	C	A	5: 43,277,587	P600Q	probably damaging	Het
Cyp2a5	C	T	7: 26,839,033	R274*	probably null	Het
Dexi	A	G	16: 10,542,518	F58S	probably damaging	Het
Dlg5	C	A	14: 24,148,300	G1522W	probably damaging	Het
Dock2	T	C	11: 34,294,286	H1048R	probably benign	Het
Dpp4	T	C	2: 62,345,050		probably benign	Het
Dusp10	A	T	1: 184,069,180	K381N	possibly damaging	Het
Ercc4	A	G	16: 13,147,787	E761G	probably damaging	Het
Ern2	T	C	7: 122,183,842		probably benign	Het
Fam83f	A	T	15: 80,692,080	T311S	probably damaging	Het
Fat2	T	C	11: 55,262,178	D3736G	probably benign	Het
Fgf11	G	T	11: 69,801,453	T58K	probably benign	Het
Galntl5	C	G	5: 25,198,532	S167*	probably null	Het
Glg1	T	G	8: 111,165,674	E846D	probably benign	Het
Grm8	C	A	6: 28,125,895	E77D	probably damaging	Het
Hmcn1	A	T	1: 150,657,451	D3028E	probably damaging	Het
Htt	A	G	5: 34,907,085	I2943V	probably benign	Het
Ift80	T	C	3: 68,918,513	K498R	probably benign	Het
Ipo9	A	T	1: 135,400,146	M509K	probably damaging	Het
Kcnj3	T	C	2: 55,437,244	V15A	probably damaging	Het
Kcnn3	A	T	3: 89,520,455		probably benign	Het
Larp1b	T	A	3: 40,964,084	D53E	probably benign	Het
Ltf	T	C	9: 111,022,845	F117L	possibly damaging	Het
Maml1	A	G	11: 50,266,130	L406P	probably damaging	Het
Mnx1	G	A	5: 29,473,957	A376V	unknown	Het
Mroh2a	G	A	1: 88,235,376	R376H	probably benign	Het
Mrpl4	A	G	9: 21,006,831	Y111C	probably damaging	Het
Mto1	T	C	9: 78,461,517		probably benign	Het
Nalcn	A	T	14: 123,316,126	M972K	possibly damaging	Het
Nemf	T	C	12: 69,346,378	I225V	probably null	Het
Nipal4	T	G	11: 46,150,231	D379A	probably damaging	Het
Nktr	A	G	9: 121,748,866		probably benign	Het
Nlrp5	A	G	7: 23,404,797	T28A	probably benign	Het
Nxph1	T	A	6: 9,247,622	Y198N	probably damaging	Het
Olfr1037	A	T	2: 86,085,720	V19D	probably benign	Het
Olfr1230	T	C	2: 89,296,670	N200S	probably damaging	Het
Olfr1436	T	C	19: 12,298,343	Y263C	probably damaging	Het
P2rx7	A	G	5: 122,673,736	Y370C	probably benign	Het
Piezo1	T	C	8: 122,482,645		probably benign	Het
Piezo1	T	C	8: 122,489,566	D1401G	probably damaging	Het
Plxnd1	A	G	6: 115,969,363	L879P	probably benign	Het
Polr2a	A	T	11: 69,743,946	I636N	probably damaging	Het
Prex2	G	T	1: 11,162,366	E886*	probably null	Het
Proca1	A	T	11: 78,205,021	I73F	probably damaging	Het
Prss55	A	T	14: 64,079,390	V101E	probably benign	Het
Psg26	T	A	7: 18,478,425	H335L	probably benign	Het
Rai1	A	G	11: 60,185,920	E270G	probably benign	Het
Reep1	A	G	6: 71,780,797	N127D	probably benign	Het
Rims1	G	T	1: 22,428,474	P769Q	probably damaging	Het
Robo4	A	T	9: 37,404,070		probably benign	Het
Ryr2	A	T	13: 11,591,336	D888E	probably benign	Het
Scamp3	A	G	3: 89,180,260	N135D	probably damaging	Het
Sdk2	C	T	11: 113,838,646		silent	Het
Sema4f	A	G	6: 82,918,029	M395T	probably benign	Het
Sgip1	T	C	4: 102,968,337		probably null	Het
Sik2	A	T	9: 50,995,674		probably benign	Het
Smtn	G	T	11: 3,531,326	A223D	possibly damaging	Het
Spen	T	C	4: 141,470,343	T3405A	probably benign	Het
Srsf11	A	T	3: 158,031,580		probably benign	Het
Tacc2	T	G	7: 130,624,202	S891R	possibly damaging	Het
Tbc1d17	T	A	7: 44,841,633		probably benign	Het
Tgfbr3l	C	A	8: 4,249,600	R128S	probably damaging	Het
Thsd1	G	A	8: 22,252,318		probably benign	Het
Tlx3	T	C	11: 33,203,072	S130G	probably benign	Het
Tmem25	A	T	9: 44,798,216		probably null	Het
Trak2	A	T	1: 58,946,336	M1K	probably null	Het
Trappc12	C	T	12: 28,746,985	E183K	probably damaging	Het
Ubl3	A	G	5: 148,509,280	V71A	possibly damaging	Het
Unc50	A	G	1: 37,438,799	Y254C	probably damaging	Het
Unkl	T	C	17: 25,229,460		probably null	Het
Uso1	T	A	5: 92,201,192	S819T	probably benign	Het
Yes1	A	T	5: 32,645,051	R103S	probably damaging	Het
Zfp131	A	G	13: 119,767,025	V396A	probably damaging	Het
Zfp553	T	C	7: 127,235,654	I127T	possibly damaging	Het
Zfp599	A	T	9: 22,251,549	N102K	probably benign	Het
Zmynd10	A	T	9: 107,550,037	Q288L	probably benign	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
R1466:Srebf1	UTSW	11	60200702	missense	probably benign	0.01
R1584:Srebf1	UTSW	11	60200702	missense	probably benign	0.01
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'- TACTTGCCTGCAAAGTGGG -3'
(R):5'- TCAGAGCTCCTGACTCTAGG -3'

Sequencing Primer
(F):5'- CCTGCAAAGTGGGTGAGGC -3'
(R):5'- ACTCTAGGGGCCCAGACAAG -3'

Posted On

2014-07-14