Mutagenetix > Incidental Mutation

Incidental Mutation 'T0722:Sim2'

67353

Institutional Source

Beutler Lab

Gene Symbol

Sim2

Ensembl Gene

ENSMUSG00000062713

Gene Name

single-minded family bHLH transcription factor 2

Synonyms

bHLHe15

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

T0722 (G3) of strain 711

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

93885963-93927891 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 93910281 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Asparagine at position 228 (H228N)

Ref Sequence

ENSEMBL: ENSMUSP00000072043 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000072182] [ENSMUST00000231688]

AlphaFold

Q61079

Predicted Effect

probably benign
Transcript: ENSMUST00000072182
AA Change: H228N

PolyPhen 2 Score 0.022 (Sensitivity: 0.95; Specificity: 0.81)

SMART Domains

Protein: ENSMUSP00000072043
Gene: ENSMUSG00000062713
AA Change: H228N

Domain	Start	End	E-Value	Type
HLH	6	58	6.99e-5	SMART
PAS	79	145	7.8e-13	SMART
PAS	220	286	1.31e-5	SMART
PAC	292	335	2.44e-5	SMART
Pfam:SIM_C	358	650	4.5e-89	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000231688
AA Change: H228N

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.5%
3x: 98.9%
10x: 97.6%
20x: 95.5%

Validation Efficiency

95% (42/44)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene represents a homolog of the Drosophila single-minded (sim) gene, which encodes a transcription factor that is a master regulator of neurogenesis. The encoded protein is ubiquitinated by RING-IBR-RING-type E3 ubiquitin ligases, including the parkin RBR E3 ubiquitin protein ligase. This gene maps within the so-called Down syndrome chromosomal region, and is thus thought to contribute to some specific Down syndrome phenotypes. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]
PHENOTYPE: Homozygous mutation of this gene results in postnatal lethality, cleft palate, malformed pterygoid processes, and aerophagia. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 72 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam6b	A	G	12: 113,453,197 (GRCm39)	T5A	possibly damaging	Het
Adam6b	T	A	12: 113,454,888 (GRCm39)	D568E	probably benign	Het
Ago3	C	T	4: 126,298,056 (GRCm39)	V155I	probably benign	Het
Ago3	G	A	4: 126,298,103 (GRCm39)	A139V	probably benign	Het
Ago3	C	T	4: 126,298,098 (GRCm39)	A141T	probably benign	Het
Ago3	T	G	4: 126,298,089 (GRCm39)	T144P	probably benign	Het
Ahdc1	ACCTCCT	ACCTCCTCCT	4: 132,790,065 (GRCm39)		probably benign	Het
Atp6v1g3	T	A	1: 138,201,591 (GRCm39)		probably benign	Het
Azin2	A	G	4: 128,839,927 (GRCm39)	Y222H	probably benign	Het
Bicd2	C	A	13: 49,533,127 (GRCm39)	P571Q	probably benign	Het
Camta2	A	G	11: 70,574,831 (GRCm39)	I75T	probably damaging	Het
Casp1	A	T	9: 5,299,851 (GRCm39)	H108L	probably benign	Het
Cdk5r1	G	T	11: 80,368,707 (GRCm39)	V125F	probably benign	Het
Cherp	TTGGACCTGGACCTGGACCTGGACCTGGA	TTGGACCTGGACCTGGACCTGGA	8: 73,215,878 (GRCm39)		probably benign	Het
Cngb1	A	G	8: 96,023,278 (GRCm39)	M240T	probably benign	Het
Cngb1	G	A	8: 96,030,342 (GRCm39)		probably benign	Het
Cngb1	T	C	8: 96,030,324 (GRCm39)		probably benign	Het
Cngb1	G	T	8: 96,024,447 (GRCm39)	Q205K	probably damaging	Het
Cog8	G	T	8: 107,775,625 (GRCm39)	L580I	probably benign	Het
Copa	A	G	1: 171,939,515 (GRCm39)	E593G	possibly damaging	Het
Ctrc	T	TA	4: 141,572,507 (GRCm39)		probably null	Het
Cwf19l2	T	C	9: 3,456,755 (GRCm39)	F696S	probably benign	Het
Ddi2	G	A	4: 141,440,784 (GRCm39)		probably benign	Het
Eml5	T	C	12: 98,807,841 (GRCm39)	D984G	probably null	Het
Fam135b	T	G	15: 71,335,734 (GRCm39)	T487P	probably damaging	Het
Fstl3	A	G	10: 79,615,997 (GRCm39)	Y161C	probably damaging	Het
Gja4	G	C	4: 127,206,024 (GRCm39)	H246Q	probably benign	Het
Gm8186	C	T	17: 26,318,101 (GRCm39)	R32Q	probably benign	Het
Jakmip1	C	A	5: 37,276,247 (GRCm39)	A519D	probably damaging	Het
Jcad	G	T	18: 4,675,531 (GRCm39)	A1098S	probably benign	Het
Klhl14	T	C	18: 21,691,192 (GRCm39)	Y446C	probably damaging	Het
Lims1	A	G	10: 58,254,277 (GRCm39)	N344D	probably benign	Het
Marco	A	T	1: 120,402,441 (GRCm39)	W502R	probably damaging	Het
Mmp13	G	T	9: 7,280,857 (GRCm39)	M413I	possibly damaging	Het
Mmp25	G	A	17: 23,850,192 (GRCm39)	A456V	possibly damaging	Het
Msi2	A	T	11: 88,285,423 (GRCm39)	M207K	probably damaging	Het
Myh8	G	A	11: 67,195,262 (GRCm39)	R1692Q	probably benign	Het
Nbas	A	G	12: 13,402,809 (GRCm39)	I788V	probably benign	Het
Nup188	A	G	2: 30,212,693 (GRCm39)	D632G	probably damaging	Het
Opa1	T	C	16: 29,429,748 (GRCm39)		probably null	Het
Or12k7	T	G	2: 36,958,449 (GRCm39)	L44R	probably damaging	Het
Or1n2	T	C	2: 36,797,582 (GRCm39)	V208A	probably benign	Het
Or4c114	A	G	2: 88,905,303 (GRCm39)	V44A	probably benign	Het
Or5w17	T	A	2: 87,583,467 (GRCm39)	Y290F	probably damaging	Het
Pabpc1l	G	A	2: 163,884,340 (GRCm39)	G359D	possibly damaging	Het
Plekhm2	TTCCTCCTCCT	TTCCTCCT	4: 141,359,292 (GRCm39)		probably benign	Het
Pomgnt1	C	T	4: 115,994,624 (GRCm39)		probably benign	Het
Psma5-ps	A	G	10: 85,149,457 (GRCm39)		noncoding transcript	Het
Qser1	A	G	2: 104,617,177 (GRCm39)	C1122R	possibly damaging	Het
Rfx8	A	G	1: 39,722,772 (GRCm39)	S282P	probably damaging	Het
Sec14l2	C	T	11: 4,053,673 (GRCm39)		probably null	Het
Slc15a2	A	G	16: 36,772,445 (GRCm38)	M179T	probably benign	Het
Slc30a6	T	A	17: 74,719,319 (GRCm39)		probably null	Het
Smarcc1	G	A	9: 110,035,153 (GRCm39)	E859K	possibly damaging	Het
Snx1	CTT	CTTGTT	9: 66,012,209 (GRCm39)		probably benign	Het
Spen	A	G	4: 141,201,664 (GRCm39)	V2321A	probably benign	Het
Spta1	A	G	1: 174,018,632 (GRCm39)		probably benign	Het
Sytl1	C	A	4: 132,984,162 (GRCm39)		probably benign	Het
Sytl1	A	G	4: 132,984,164 (GRCm39)		probably benign	Het
Tent4a	G	A	13: 69,655,074 (GRCm39)	R224*	probably null	Het
Terf2	T	C	8: 107,803,306 (GRCm39)	K425E	probably benign	Het
Tmem26	A	G	10: 68,614,548 (GRCm39)	E321G	probably benign	Het
Toe1	T	C	4: 116,663,290 (GRCm39)	I62M	probably benign	Het
Uck2	A	T	1: 167,062,280 (GRCm39)	D149E	probably benign	Het
Wnt5a	G	A	14: 28,233,882 (GRCm39)	A17T	probably benign	Het
Yif1b	T	C	7: 28,938,038 (GRCm39)		probably null	Het
Zbtb8a	T	C	4: 129,254,005 (GRCm39)	H163R	probably benign	Het
Zbtb8a	GG	GGATG	4: 129,253,812 (GRCm39)		probably benign	Het
Zkscan4	AGAGGAG	AGAG	13: 21,663,370 (GRCm39)		probably benign	Het
Zmym1	A	C	4: 126,943,466 (GRCm39)	H307Q	probably benign	Het
Zmym1	C	T	4: 126,941,740 (GRCm39)	D785N	probably benign	Het
Zmym1	C	T	4: 126,942,043 (GRCm39)	V684I	probably benign	Het

Other mutations in Sim2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00332:Sim2	APN	16	93,915,803 (GRCm39)	nonsense	probably null
IGL01329:Sim2	APN	16	93,907,119 (GRCm39)	missense	possibly damaging	0.64
IGL01965:Sim2	APN	16	93,922,037 (GRCm39)	missense	probably benign	0.20
IGL01979:Sim2	APN	16	93,924,341 (GRCm39)	missense	possibly damaging	0.81
IGL02821:Sim2	APN	16	93,898,047 (GRCm39)	missense	probably damaging	1.00
IGL03027:Sim2	APN	16	93,910,351 (GRCm39)	splice site	probably benign
P0027:Sim2	UTSW	16	93,910,281 (GRCm39)	missense	probably benign	0.02
PIT4696001:Sim2	UTSW	16	93,895,168 (GRCm39)	missense	possibly damaging	0.49
R1836:Sim2	UTSW	16	93,924,436 (GRCm39)	critical splice donor site	probably null
R2034:Sim2	UTSW	16	93,886,801 (GRCm39)	missense	probably damaging	0.96
R4085:Sim2	UTSW	16	93,910,213 (GRCm39)	missense	possibly damaging	0.48
R4475:Sim2	UTSW	16	93,926,650 (GRCm39)	missense	probably benign
R4476:Sim2	UTSW	16	93,926,650 (GRCm39)	missense	probably benign
R4647:Sim2	UTSW	16	93,924,385 (GRCm39)	missense	possibly damaging	0.71
R4919:Sim2	UTSW	16	93,910,194 (GRCm39)	missense	probably benign	0.01
R4966:Sim2	UTSW	16	93,924,280 (GRCm39)	missense	probably benign	0.03
R5320:Sim2	UTSW	16	93,905,598 (GRCm39)	missense	probably benign	0.01
R5555:Sim2	UTSW	16	93,910,315 (GRCm39)	missense	probably damaging	1.00
R5591:Sim2	UTSW	16	93,898,048 (GRCm39)	missense	probably damaging	1.00
R5870:Sim2	UTSW	16	93,924,193 (GRCm39)	missense	probably damaging	0.99
R6020:Sim2	UTSW	16	93,898,110 (GRCm39)	missense	probably damaging	1.00
R6302:Sim2	UTSW	16	93,898,089 (GRCm39)	missense	probably damaging	1.00
R6883:Sim2	UTSW	16	93,926,395 (GRCm39)	missense	probably benign	0.00
R7170:Sim2	UTSW	16	93,923,559 (GRCm39)	missense	probably benign	0.00
R7559:Sim2	UTSW	16	93,910,218 (GRCm39)	missense	possibly damaging	0.95
R7740:Sim2	UTSW	16	93,915,819 (GRCm39)	missense	probably benign	0.25
R8114:Sim2	UTSW	16	93,923,503 (GRCm39)	missense	probably benign	0.00
R8244:Sim2	UTSW	16	93,910,222 (GRCm39)	missense	probably damaging	0.99
R8682:Sim2	UTSW	16	93,924,192 (GRCm39)	missense	probably benign	0.23
X0063:Sim2	UTSW	16	93,923,557 (GRCm39)	missense	possibly damaging	0.89

Predicted Primers

PCR Primer
(F):5'- GAACTTGGGTGAAGGATGGCCTAC -3'
(R):5'- CGTATGGTCAGTGTGCATCACAAGC -3'

Sequencing Primer
(F):5'- GGATGGCCTACCACTTCAAAAAC -3'
(R):5'- GTGTGCATCACAAGCTTACAATC -3'

Nature of Mutation

ACGGAGATCAAGCTCCACAGCAACATGTTCATG

223 -T--E--I--K--L--H--S--N--M--F--M-

Genotyping

NOTE: These primers have not been validated.

T0722:Sim2 genotyping is performed by amplifying the region containing the mutation using PCR, followed by sequencing of the amplified region to detect the single nucleotide transition.

PCR Primers

T07220040_Sim2_PCR_F: 5’- GAACTTGGGTGAAGGATGGCCTAC-3’

T07220040_Sim2_PCR_R: 5’- CGTATGGTCAGTGTGCATCACAAGC-3’

Sequencing Primers

T07220040_Sim2_SEQ_F: 5’- GGATGGCCTACCACTTCAAAAAC-3’ 

T07220040_Sim2_SEQ_R: 5’- GTGTGCATCACAAGCTTACAATC-3’ 

PCR program

1) 94°C 2:00

2) 94°C 0:30

3) 55°C 0:30

4) 72°C 1:00

5) repeat steps (2-4) 40X

6) 72°C 10:00

7) 4°C hold

The following sequence of 502 nucleotides is amplified (Chr.16: 94109175-94109676, GRCm38; NCBI RefSeq: NC_000082):

gaacttgggt gaaggatggc ctaccacttc aaaaacaaat gaacaaacaa agccaaaaaa

agctaaggca gagcggtggt gccccctgag cctgtgtctt ccttcccagg tcattcactg

cagcggctac ctaaagatca gacagtacat gctggacatg tccctgtacg actcctgtta

ccagatcgtg gggctggtgg ccgtgggcca gtcgctaccg cccagcgcca tcacggagat

caagctccac agcaacatgt tcatgttcag ggccagcctt gacctgaagc tcatattcct

ggactccagg tgagtctgcc tggccccagc tgtcaccatt gctgtgactg cccagaaagc

cccggtgctg gaactggtcg cagatgagca aggaagttag tcatgaggta aagaattcag

gacagactta agatgcagga acttgtttta atgaattgcc taatgtttgg attgtaagct

tgtgatgcac actgaccata cg

FASTA sequence

Primer binding sites are underlined and the sequencing primer is highlighted; the mutated C is shown in red text (C>A).

Posted On

2013-09-03