Mutagenetix > Incidental Mutation

Incidental Mutation 'R1573:Smad2'

171006

Institutional Source

Beutler Lab

Gene Symbol

Smad2

Ensembl Gene

ENSMUSG00000024563

Gene Name

SMAD family member 2

Synonyms

Madr2, Madh2, Smad 2, 7120426M23Rik

MMRRC Submission

039612-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1573 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

76374651-76444034 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 76395657 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Glycine at position 32 (E32G)

Ref Sequence

ENSEMBL: ENSMUSP00000130115 (fasta)

Gene Model

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

AlphaFold

Q62432

Predicted Effect

possibly damaging
Transcript: ENSMUST00000025453
AA Change: E32G

PolyPhen 2 Score 0.894 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000025453
Gene: ENSMUSG00000024563
AA Change: E32G

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

possibly damaging
Transcript: ENSMUST00000091831
AA Change: E32G

PolyPhen 2 Score 0.894 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000089439
Gene: ENSMUSG00000024563
AA Change: E32G

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: E32G

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

SMART Domains

Protein: ENSMUSP00000109563
Gene: ENSMUSG00000024563
AA Change: E32G

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: E32G

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)

SMART Domains

Protein: ENSMUSP00000132851
Gene: ENSMUSG00000024563
AA Change: E32G

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

possibly damaging
Transcript: ENSMUST00000168423
AA Change: E32G

PolyPhen 2 Score 0.894 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000130115
Gene: ENSMUSG00000024563
AA Change: E32G

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: E32G

PolyPhen 2 Score 0.034 (Sensitivity: 0.95; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000125883
Gene: ENSMUSG00000024563
AA Change: E32G

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

0.0979

Coding Region Coverage

1x: 98.9%
3x: 97.8%
10x: 94.6%
20x: 87.1%

Validation Efficiency

98% (90/92)

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: 82 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam19	T	C	11: 46,004,445 (GRCm39)		probably benign	Het
Add1	C	G	5: 34,758,740 (GRCm39)	A18G	possibly damaging	Het
Alk	T	C	17: 72,910,113 (GRCm39)	K198E	possibly damaging	Het
Angptl1	T	A	1: 156,684,740 (GRCm39)	L303Q	possibly damaging	Het
Aox1	A	T	1: 58,348,186 (GRCm39)	I635L	probably benign	Het
Atp5mk	T	A	19: 47,074,634 (GRCm39)	Q9L	possibly damaging	Het
Atp8a2	G	T	14: 60,097,655 (GRCm39)	T791K	probably benign	Het
Auts2	T	C	5: 131,469,325 (GRCm39)	K664R	probably damaging	Het
Birc6	T	A	17: 74,967,685 (GRCm39)		probably benign	Het
Cacna1i	C	A	15: 80,277,869 (GRCm39)		probably null	Het
Cacna2d1	T	C	5: 16,575,625 (GRCm39)	F1077L	probably damaging	Het
Camkk1	C	T	11: 72,918,307 (GRCm39)	R52C	probably damaging	Het
Camkmt	T	A	17: 85,403,958 (GRCm39)	V60E	probably damaging	Het
Car9	G	T	4: 43,512,439 (GRCm39)		probably null	Het
Cbr2	A	T	11: 120,622,791 (GRCm39)	L3Q	possibly damaging	Het
Ccar1	A	T	10: 62,586,434 (GRCm39)	D920E	unknown	Het
Cdc20b	A	G	13: 113,192,478 (GRCm39)	N57S	probably benign	Het
Cep83	G	A	10: 94,624,525 (GRCm39)	E601K	probably damaging	Het
Cldn10	A	T	14: 119,111,080 (GRCm39)	I176L	probably benign	Het
Cpeb2	T	C	5: 43,441,273 (GRCm39)		probably benign	Het
Crb1	A	G	1: 139,265,344 (GRCm39)	S25P	probably damaging	Het
Cyp3a59	A	T	5: 146,039,684 (GRCm39)	Y319F	probably damaging	Het
Dst	C	T	1: 34,240,312 (GRCm39)	S1561F	probably damaging	Het
Dxo	C	T	17: 35,057,270 (GRCm39)	R221C	probably damaging	Het
Dynlt4	A	T	4: 116,985,191 (GRCm39)	T5S	probably benign	Het
Epc2	A	G	2: 49,439,984 (GRCm39)	T801A	possibly damaging	Het
Fndc3a	C	A	14: 72,806,384 (GRCm39)	C373F	probably damaging	Het
Frmpd1	T	C	4: 45,283,932 (GRCm39)	S918P	probably benign	Het
Fuca2	A	G	10: 13,381,587 (GRCm39)	T84A	possibly damaging	Het
Garin4	G	A	1: 190,896,682 (GRCm39)		probably benign	Het
Gmeb1	A	T	4: 131,979,051 (GRCm39)	N21K	probably benign	Het
Htt	T	C	5: 35,021,718 (GRCm39)		probably benign	Het
Igsf1	T	C	X: 48,880,863 (GRCm39)	R251G	possibly damaging	Het
Itih4	A	T	14: 30,619,504 (GRCm39)	H720L	probably benign	Het
Kank4	A	T	4: 98,663,073 (GRCm39)	L705*	probably null	Het
Krt34	A	T	11: 99,931,854 (GRCm39)	S122T	probably benign	Het
L1td1	A	G	4: 98,625,517 (GRCm39)	T571A	probably benign	Het
Lag3	T	C	6: 124,886,210 (GRCm39)	T248A	possibly damaging	Het
Lgi1	T	A	19: 38,272,629 (GRCm39)	H133Q	probably benign	Het
Map1a	A	T	2: 121,134,607 (GRCm39)	T1808S	probably benign	Het
Mcm9	T	C	10: 53,424,752 (GRCm39)	T613A	probably damaging	Het
Meaf6	A	G	4: 124,983,931 (GRCm39)	I111V	probably benign	Het
Mki67	G	A	7: 135,296,845 (GRCm39)	P2730S	possibly damaging	Het
Mlc1	A	C	15: 88,842,350 (GRCm39)	C337G	probably damaging	Het
Mrc2	T	A	11: 105,227,482 (GRCm39)	Y572N	probably damaging	Het
Mterf3	T	C	13: 67,070,967 (GRCm39)	N172S	possibly damaging	Het
Or3a1c	T	A	11: 74,046,196 (GRCm39)	M72K	probably benign	Het
Or4b1	A	T	2: 89,979,068 (GRCm39)		probably benign	Het
Or4c115	T	A	2: 88,928,064 (GRCm39)	D69V	probably damaging	Het
Or5ak4	A	T	2: 85,161,687 (GRCm39)	L185H	probably damaging	Het
Or6c6c	T	C	10: 129,541,487 (GRCm39)	S247P	probably damaging	Het
Padi4	T	G	4: 140,484,881 (GRCm39)	T327P	possibly damaging	Het
Pga5	T	A	19: 10,651,201 (GRCm39)	I151F	probably benign	Het
Pkdrej	G	T	15: 85,702,275 (GRCm39)	D1220E	probably benign	Het
Prokr2	T	A	2: 132,215,684 (GRCm39)	Q259L	probably damaging	Het
Ptbp2	C	A	3: 119,546,754 (GRCm39)	D43Y	probably damaging	Het
Ptpro	T	A	6: 137,420,592 (GRCm39)	V1007D	probably damaging	Het
Ralgps2	C	T	1: 156,660,500 (GRCm39)	R237Q	possibly damaging	Het
Rap1gds1	C	A	3: 138,671,624 (GRCm39)		probably null	Het
Saa2	T	A	7: 46,401,716 (GRCm39)	M1K	probably null	Het
Samd9l	T	C	6: 3,375,426 (GRCm39)	I612V	probably damaging	Het
Scn10a	C	T	9: 119,442,692 (GRCm39)	V1518I	probably benign	Het
Serpina6	T	C	12: 103,618,012 (GRCm39)	D267G	probably damaging	Het
Sh2d4b	A	G	14: 40,564,329 (GRCm39)		probably null	Het
Sh3bp2	T	C	5: 34,718,034 (GRCm39)	V505A	probably benign	Het
Smn1	T	G	13: 100,263,118 (GRCm39)	D32E	probably damaging	Het
Spata31d1c	T	C	13: 65,182,883 (GRCm39)	S142P	possibly damaging	Het
Stk39	A	T	2: 68,221,293 (GRCm39)	I210N	probably damaging	Het
Tcte2	A	G	17: 13,937,899 (GRCm39)		probably benign	Het
Tctn3	C	A	19: 40,597,361 (GRCm39)	E230*	probably null	Het
Tenm2	A	T	11: 35,937,896 (GRCm39)	H1592Q	probably damaging	Het
Tescl	A	G	7: 24,032,668 (GRCm39)	V219A	probably damaging	Het
Tgm6	C	T	2: 129,993,660 (GRCm39)	S633L	probably benign	Het
Tmcc1	C	T	6: 116,110,924 (GRCm39)	S123N	probably damaging	Het
Ttn	A	T	2: 76,641,587 (GRCm39)	L5176Q	possibly damaging	Het
Ulk2	G	A	11: 61,670,581 (GRCm39)	R992C	probably damaging	Het
Vwa5b1	G	A	4: 138,332,184 (GRCm39)	H278Y	probably damaging	Het
Wwp2	C	T	8: 108,275,121 (GRCm39)	R373W	probably damaging	Het
Zfp24	A	T	18: 24,150,399 (GRCm39)	D170E	possibly damaging	Het
Zfp808	T	C	13: 62,319,311 (GRCm39)	I180T	possibly damaging	Het
Zfp820	T	A	17: 22,037,737 (GRCm39)	Q530H	probably benign	Het
Zfp975	A	T	7: 42,311,507 (GRCm39)	Y369N	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
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
R3917:Smad2	UTSW	18	76,421,008 (GRCm39)	missense	probably benign	0.42
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'- GTTAATTGCCCAGAGCGTTGACAAAG -3'
(R):5'- CGCCAACTTACCTTGGTATGGTGAC -3'

Sequencing Primer
(F):5'- AGACAGCATCGTCATCAGTATAG -3'
(R):5'- ACCTTGGTATGGTGACACATTTAG -3'

Posted On

2014-04-13