Mutagenetix > Incidental Mutation

Incidental Mutation 'R3917:Smad2'

307388

Institutional Source

Beutler Lab

Gene Symbol

Smad2

Ensembl Gene

ENSMUSG00000024563

Gene Name

SMAD family member 2

Synonyms

Madr2, Madh2, Smad 2, 7120426M23Rik

MMRRC Submission

040914-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R3917 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

76374651-76444034 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 76421008 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glutamic Acid at position 82 (D82E)

Ref Sequence

ENSEMBL: ENSMUSP00000132851 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000025453] [ENSMUST00000091831] [ENSMUST00000113930] [ENSMUST00000165084] [ENSMUST00000168423] [ENSMUST00000171256] [ENSMUST00000172198]

AlphaFold

Q62432

Predicted Effect

probably benign
Transcript: ENSMUST00000025453
AA Change: D112E

PolyPhen 2 Score 0.059 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000025453
Gene: ENSMUSG00000024563
AA Change: D112E

Domain	Start	End	E-Value	Type
DWA	36	174	1e-64	SMART
Blast:DWB	230	261	2e-10	BLAST
DWB	272	443	2.25e-108	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000091831
AA Change: D82E

PolyPhen 2 Score 0.015 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000089439
Gene: ENSMUSG00000024563
AA Change: D82E

Domain	Start	End	E-Value	Type
DWA	36	144	1.68e-66	SMART
Blast:DWB	200	231	1e-10	BLAST
DWB	242	413	2.25e-108	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000113930
AA Change: D82E

PolyPhen 2 Score 0.058 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000109563
Gene: ENSMUSG00000024563
AA Change: D82E

Domain	Start	End	E-Value	Type
DWA	36	144	1.68e-66	SMART
Blast:DWB	200	231	9e-11	BLAST
DWB	242	408	4.38e-88	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000165084
AA Change: D82E

PolyPhen 2 Score 0.417 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000132851
Gene: ENSMUSG00000024563
AA Change: D82E

Domain	Start	End	E-Value	Type
DWA	36	144	7.85e-67	SMART
PDB:1KHX\|A	166	204	3e-19	PDB
SCOP:d1khxa_	190	204	7e-4	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000168423
AA Change: D112E

PolyPhen 2 Score 0.059 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000130115
Gene: ENSMUSG00000024563
AA Change: D112E

Domain	Start	End	E-Value	Type
DWA	36	174	1e-64	SMART
Blast:DWB	230	261	2e-10	BLAST
DWB	272	443	2.25e-108	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000171256
AA Change: D112E

PolyPhen 2 Score 0.101 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000125883
Gene: ENSMUSG00000024563
AA Change: D112E

Domain	Start	End	E-Value	Type
DWA	36	174	1e-64	SMART
Blast:DWA	182	213	3e-13	BLAST

Predicted Effect

probably benign
Transcript: ENSMUST00000172198

SMART Domains

Protein: ENSMUSP00000129232
Gene: ENSMUSG00000024563

Domain	Start	End	E-Value	Type
Pfam:MH2	28	58	1.8e-10	PFAM

Meta Mutation Damage Score

0.5232

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.3%
20x: 95.0%

Validation Efficiency

97% (74/76)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the signal of the transforming growth factor (TGF)-beta, and thus regulates multiple cellular processes, such as cell proliferation, apoptosis, and differentiation. This protein is recruited to the TGF-beta receptors through its interaction with the SMAD anchor for receptor activation (SARA) protein. In response to TGF-beta signal, this protein is phosphorylated by the TGF-beta receptors. The phosphorylation induces the dissociation of this protein with SARA and the association with the family member SMAD4. The association with SMAD4 is important for the translocation of this protein into the nucleus, where it binds to target promoters and forms a transcription repressor complex with other cofactors. This protein can also be phosphorylated by activin type 1 receptor kinase, and mediates the signal from the activin. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]
PHENOTYPE: Homozygous mutant embryos die at day 6.5-8.5 with multiple defects, including failed gastrulation, lack of mesoderm, visceral endoderm dysfunction and failure to form anterior-posterior axis. Heterozygotes may show gastrulation defects and lack mandible or eyes. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 74 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acad12	A	G	5: 121,737,277 (GRCm39)	V498A	probably damaging	Het
Adam19	A	G	11: 45,951,762 (GRCm39)	E37G	probably benign	Het
Apol11b	A	G	15: 77,519,504 (GRCm39)	I192T	probably benign	Het
Appl1	A	T	14: 26,650,561 (GRCm39)	F537Y	probably damaging	Het
Atad5	A	C	11: 79,994,120 (GRCm39)	K785N	probably null	Het
Atp1b2	A	G	11: 69,493,901 (GRCm39)	V93A	probably damaging	Het
Bcam	T	C	7: 19,499,375 (GRCm39)	Y216C	probably damaging	Het
Brca2	A	G	5: 150,464,292 (GRCm39)	E1352G	probably damaging	Het
C030005K15Rik	A	C	10: 97,561,453 (GRCm39)	S93A	unknown	Het
Cadps	C	T	14: 12,457,702 (GRCm38)	A1060T	probably benign	Het
Ccdc88c	A	G	12: 100,907,366 (GRCm39)		probably null	Het
Ccdc89	A	G	7: 90,076,033 (GRCm39)	D81G	probably damaging	Het
Ccnt1	A	G	15: 98,441,940 (GRCm39)	S443P	probably benign	Het
Cd109	CATTTATTTATTTATTTATTTATTTATTTATTTAT	CATTTATTTATTTATTTATTTATTTATTTATTTATTTAT	9: 78,619,782 (GRCm39)		probably benign	Het
Cdc42bpa	T	C	1: 179,933,719 (GRCm39)		probably null	Het
Cdk11b	T	C	4: 155,711,258 (GRCm39)	S47P	probably damaging	Het
Cfap43	T	C	19: 47,886,189 (GRCm39)	D142G	probably benign	Het
Cntnap4	C	G	8: 113,602,165 (GRCm39)	P1190A	probably benign	Het
Colgalt2	T	A	1: 152,384,362 (GRCm39)	Y567*	probably null	Het
Dner	CGCTGCTGCTGCTGCTGCTGCTGCTGC	CGCTGCTGCTGCTGCTGCTGCTGC	1: 84,563,270 (GRCm39)		probably benign	Het
Dock7	T	C	4: 98,904,922 (GRCm39)	Y651C	probably damaging	Het
Fzd3	A	T	14: 65,473,379 (GRCm39)	F130I	probably damaging	Het
Gabarapl2	T	A	8: 112,679,028 (GRCm39)	F115L	probably benign	Het
Gm1043	G	A	5: 37,350,285 (GRCm39)		probably benign	Het
Gm12185	A	G	11: 48,806,760 (GRCm39)	F144L	probably benign	Het
Gm21961	A	T	15: 64,886,733 (GRCm39)	D7E	unknown	Het
Gtf3a	A	G	5: 146,892,244 (GRCm39)	K332E	probably benign	Het
Haao	A	G	17: 84,146,228 (GRCm39)		probably null	Het
Habp2	T	A	19: 56,299,611 (GRCm39)	C170S	probably damaging	Het
Heatr3	T	G	8: 88,876,999 (GRCm39)		probably null	Het
Herc1	T	G	9: 66,341,748 (GRCm39)	C1846G	possibly damaging	Het
Hivep3	T	C	4: 119,956,624 (GRCm39)	S1647P	probably benign	Het
Hnrnpul1	C	T	7: 25,426,300 (GRCm39)	R517Q	probably damaging	Het
Hspg2	A	G	4: 137,286,625 (GRCm39)	E3648G	probably damaging	Het
Jaml	T	C	9: 45,012,449 (GRCm39)		probably benign	Het
Jund	C	T	8: 71,151,673 (GRCm39)		probably benign	Het
Klra14-ps	T	C	6: 130,134,595 (GRCm39)		noncoding transcript	Het
Krt88	G	A	15: 101,350,809 (GRCm39)		probably null	Het
Lrp5	G	A	19: 3,662,330 (GRCm39)	R173C	probably damaging	Het
Lyzl4	T	A	9: 121,412,101 (GRCm39)	D105V	probably damaging	Het
Mst1	A	G	9: 107,961,494 (GRCm39)	I575V	probably benign	Het
Myd88	T	C	9: 119,170,464 (GRCm39)		probably benign	Het
Myo1d	A	T	11: 80,557,404 (GRCm39)	V512E	probably damaging	Het
Ndufv1	A	G	19: 4,060,002 (GRCm39)	Y33H	probably damaging	Het
Nwd1	T	A	8: 73,394,439 (GRCm39)	C608*	probably null	Het
Or10al2	T	A	17: 37,983,684 (GRCm39)	F257I	probably damaging	Het
Or8b37	A	T	9: 37,958,841 (GRCm39)	I108F	probably damaging	Het
Patj	A	T	4: 98,480,245 (GRCm39)	K1317*	probably null	Het
Pld5	A	G	1: 175,791,504 (GRCm39)	S501P	probably benign	Het
Pnpo	A	G	11: 96,830,583 (GRCm39)	V146A	probably damaging	Het
Ppdpf	A	G	2: 180,829,521 (GRCm39)	Y16C	probably benign	Het
Ppp1r27	A	G	11: 120,441,785 (GRCm39)	V32A	possibly damaging	Het
Rbm28	T	C	6: 29,154,788 (GRCm39)	D294G	probably benign	Het
Sdk1	T	A	5: 142,036,999 (GRCm39)	D817E	probably damaging	Het
Shank3	A	G	15: 89,387,587 (GRCm39)	D252G	possibly damaging	Het
Slc29a1	A	T	17: 45,899,899 (GRCm39)		probably null	Het
Slc35a5	G	C	16: 44,978,521 (GRCm39)		probably benign	Het
Slc6a5	T	C	7: 49,561,617 (GRCm39)	S50P	probably damaging	Het
Slfn8	A	T	11: 82,907,819 (GRCm39)	Y241*	probably null	Het
Slu7	G	T	11: 43,331,511 (GRCm39)		probably null	Het
Spx	A	C	6: 142,359,757 (GRCm39)	E33A	probably damaging	Het
Tdp1	A	G	12: 99,860,976 (GRCm39)	Y205C	probably damaging	Het
Tekt1	A	G	11: 72,236,574 (GRCm39)	I296T	possibly damaging	Het
Tgm1	G	A	14: 55,950,214 (GRCm39)		probably benign	Het
Tnks	A	G	8: 35,320,515 (GRCm39)	S719P	probably damaging	Het
Trip6	A	G	5: 137,311,941 (GRCm39)	C47R	probably benign	Het
Trpv3	A	G	11: 73,174,560 (GRCm39)	D309G	possibly damaging	Het
Tti2	A	G	8: 31,643,547 (GRCm39)	K221E	possibly damaging	Het
Ugcg	C	T	4: 59,207,798 (GRCm39)	P46S	probably benign	Het
Vmn1r57	A	T	7: 5,223,630 (GRCm39)	N52Y	probably damaging	Het
Vmn2r94	A	G	17: 18,464,620 (GRCm39)	F557L	probably benign	Het
Zbed5	T	C	5: 129,931,118 (GRCm39)	Y356H	possibly damaging	Het
Zfp1005	T	A	2: 150,108,039 (GRCm39)		probably benign	Het
Zic4	C	A	9: 91,266,394 (GRCm39)		probably benign	Het

Other mutations in Smad2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00429:Smad2	APN	18	76,431,566 (GRCm39)	missense	possibly damaging	0.94
IGL00978:Smad2	APN	18	76,432,846 (GRCm39)	splice site	probably benign
IGL01295:Smad2	APN	18	76,435,501 (GRCm39)	missense	probably benign	0.05
IGL01887:Smad2	APN	18	76,432,965 (GRCm39)	missense	probably damaging	1.00
IGL01960:Smad2	APN	18	76,395,555 (GRCm39)	intron	probably benign
IGL02881:Smad2	APN	18	76,432,851 (GRCm39)	splice site	probably null
IGL02977:Smad2	APN	18	76,422,235 (GRCm39)	missense	possibly damaging	0.64
R0333:Smad2	UTSW	18	76,395,692 (GRCm39)	missense	probably damaging	1.00
R0391:Smad2	UTSW	18	76,422,108 (GRCm39)	critical splice acceptor site	probably null
R0523:Smad2	UTSW	18	76,395,623 (GRCm39)	missense	probably benign
R0570:Smad2	UTSW	18	76,422,250 (GRCm39)	splice site	probably benign
R0624:Smad2	UTSW	18	76,433,064 (GRCm39)	missense	probably damaging	1.00
R1573:Smad2	UTSW	18	76,395,657 (GRCm39)	missense	possibly damaging	0.89
R1953:Smad2	UTSW	18	76,395,776 (GRCm39)	missense	possibly damaging	0.90
R2132:Smad2	UTSW	18	76,421,155 (GRCm39)	nonsense	probably null
R2213:Smad2	UTSW	18	76,437,697 (GRCm39)	missense	probably damaging	1.00
R3021:Smad2	UTSW	18	76,395,703 (GRCm39)	missense	probably damaging	1.00
R4503:Smad2	UTSW	18	76,435,663 (GRCm39)	missense	probably benign	0.23
R5253:Smad2	UTSW	18	76,421,124 (GRCm39)	missense	probably damaging	1.00
R5290:Smad2	UTSW	18	76,395,795 (GRCm39)	missense	probably damaging	1.00
R5891:Smad2	UTSW	18	76,433,046 (GRCm39)	missense	probably damaging	1.00
R6294:Smad2	UTSW	18	76,422,233 (GRCm39)	missense	probably benign	0.31
R6879:Smad2	UTSW	18	76,395,725 (GRCm39)	missense	possibly damaging	0.49
R7430:Smad2	UTSW	18	76,421,151 (GRCm39)	missense	probably damaging	1.00
R7503:Smad2	UTSW	18	76,419,956 (GRCm39)	missense	probably benign
R7757:Smad2	UTSW	18	76,421,084 (GRCm39)	missense	probably benign	0.40
R8072:Smad2	UTSW	18	76,420,022 (GRCm39)	critical splice donor site	probably null
R9132:Smad2	UTSW	18	76,395,573 (GRCm39)	missense	possibly damaging	0.87
R9159:Smad2	UTSW	18	76,395,573 (GRCm39)	missense	possibly damaging	0.87
R9184:Smad2	UTSW	18	76,422,171 (GRCm39)	missense	probably benign	0.00
Z1177:Smad2	UTSW	18	76,421,074 (GRCm39)	missense	probably damaging	1.00
Z1177:Smad2	UTSW	18	76,421,073 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CACACTGATAGAGGACAGGC -3'
(R):5'- GTTTCCTACCTGGGGTCTCAAC -3'

Sequencing Primer
(F):5'- AAGGGCCACTGCTTGCTCTATC -3'
(R):5'- CTCAACTCTCTGGTAGTGGTACG -3'

Posted On

2015-04-17