Mutagenetix > Incidental Mutation

Incidental Mutation 'R1742:Smad4'

200469

Institutional Source

Beutler Lab

Gene Symbol

Smad4

Ensembl Gene

ENSMUSG00000024515

Gene Name

SMAD family member 4

Synonyms

Dpc4, D18Wsu70e, DPC4, Smad 4, Madh4

MMRRC Submission

039774-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1742 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

73772080-73836851 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 73808968 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Glycine at position 100 (R100G)

Ref Sequence

ENSEMBL: ENSMUSP00000110589 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000025393] [ENSMUST00000114939]

AlphaFold

P97471

Predicted Effect

probably damaging
Transcript: ENSMUST00000025393
AA Change: R100G

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

SMART Domains

Protein: ENSMUSP00000025393
Gene: ENSMUSG00000024515
AA Change: R100G

Domain	Start	End	E-Value	Type
DWA	31	140	5.77e-65	SMART
low complexity region	286	299	N/A	INTRINSIC
DWB	320	529	1.41e-123	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000114939
AA Change: R100G

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

SMART Domains

Protein: ENSMUSP00000110589
Gene: ENSMUSG00000024515
AA Change: R100G

Domain	Start	End	E-Value	Type
DWA	31	140	5.77e-65	SMART
low complexity region	286	299	N/A	INTRINSIC
DWB	320	529	1.41e-123	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000129326

Coding Region Coverage

1x: 97.5%
3x: 96.9%
10x: 95.4%
20x: 92.7%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the Smad family of signal transduction proteins. Smad proteins are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to TGF-beta signaling. The product of this gene forms homomeric complexes and heteromeric complexes with other activated Smad proteins, which then accumulate in the nucleus and regulate the transcription of target genes. This protein binds to DNA and recognizes an 8-bp palindromic sequence (GTCTAGAC) called the Smad-binding element (SBE). The Smad proteins are subject to complex regulation by post-translational modifications. Mutations or deletions in this gene have been shown to result in pancreatic cancer, juvenile polyposis syndrome, and hereditary hemorrhagic telangiectasia syndrome. [provided by RefSeq, Oct 2009]
PHENOTYPE: Homozygotes for targeted null mutations exhibit impaired formation of extraembryonic membrane and endoderm and die prior to gastrulation. Heterozygotes develop polyposis of the glandular stomach and duodenum. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 69 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Ankhd1	C	A	18: 36,758,318 (GRCm39)	A1004E	probably damaging	Het
Arfgef2	A	G	2: 166,708,900 (GRCm39)	S1071G	probably damaging	Het
Arhgef5	T	A	6: 43,257,133 (GRCm39)	I1228N	probably damaging	Het
Auh	G	A	13: 52,989,532 (GRCm39)	P308L	probably benign	Het
Bptf	A	G	11: 107,001,777 (GRCm39)	V445A	probably damaging	Het
Btf3	C	T	13: 98,452,804 (GRCm39)	M1I	probably null	Het
Bves	C	T	10: 45,223,961 (GRCm39)	T207M	probably damaging	Het
Ccdc171	T	A	4: 83,599,521 (GRCm39)	S779T	probably damaging	Het
Ccdc54	T	C	16: 50,410,601 (GRCm39)	K222E	possibly damaging	Het
Cebpe	A	G	14: 54,949,057 (GRCm39)	V120A	probably benign	Het
Clhc1	T	A	11: 29,507,647 (GRCm39)		probably null	Het
Col22a1	C	T	15: 71,673,762 (GRCm39)	G985S	unknown	Het
Col6a3	T	A	1: 90,741,516 (GRCm39)	I639F	probably damaging	Het
Cryga	C	A	1: 65,142,280 (GRCm39)	V38L	probably benign	Het
Dll3	T	C	7: 27,993,848 (GRCm39)	T530A	probably benign	Het
Dnaaf9	A	T	2: 130,582,315 (GRCm39)		probably null	Het
Dnah7a	G	A	1: 53,495,843 (GRCm39)	P3205S	probably benign	Het
Dpp10	T	A	1: 123,372,935 (GRCm39)	Y224F	probably damaging	Het
Eif1ad10	C	T	12: 88,216,453 (GRCm39)	D140N	unknown	Het
Fcrl2	T	C	3: 87,166,350 (GRCm39)	T142A	possibly damaging	Het
Fyttd1	C	T	16: 32,725,923 (GRCm39)	R175*	probably null	Het
Gm10277	TC	T	11: 77,676,828 (GRCm39)		probably null	Het
Gpr33	T	C	12: 52,071,045 (GRCm39)		probably null	Het
Gse1	T	A	8: 121,293,689 (GRCm39)	V205E	probably damaging	Het
Herc4	C	A	10: 63,123,728 (GRCm39)	N461K	probably benign	Het
Ifi206	G	A	1: 173,309,537 (GRCm39)	T153I	probably benign	Het
Iqca1	T	C	1: 90,025,773 (GRCm39)	I341V	probably benign	Het
Itsn1	T	G	16: 91,613,847 (GRCm39)		probably null	Het
Kcnk5	T	A	14: 20,191,925 (GRCm39)	Y412F	probably benign	Het
Lemd1	T	A	1: 132,156,036 (GRCm39)	I26K	probably damaging	Het
Lipc	A	T	9: 70,727,811 (GRCm39)	L12Q	probably damaging	Het
Lrrtm1	C	A	6: 77,221,074 (GRCm39)	P177Q	probably damaging	Het
Mcph1	G	A	8: 18,657,379 (GRCm39)	G73R	probably benign	Het
Msantd5f6	T	C	4: 73,319,447 (GRCm39)	D99G	probably damaging	Het
Myh11	A	T	16: 14,037,908 (GRCm39)	L899Q	probably damaging	Het
Myo18a	G	T	11: 77,732,293 (GRCm39)	R822L	probably damaging	Het
Nav3	T	C	10: 109,605,074 (GRCm39)	T1000A	probably benign	Het
Nox4	T	C	7: 86,945,026 (GRCm39)	V94A	possibly damaging	Het
Or10ag53	T	A	2: 87,083,122 (GRCm39)	N280K	probably benign	Het
Or4c123	G	T	2: 89,126,768 (GRCm39)	P282H	probably damaging	Het
Or7g32	A	G	9: 19,389,337 (GRCm39)	S67P	probably damaging	Het
Oxr1	T	C	15: 41,713,955 (GRCm39)	L679P	probably damaging	Het
Pcdhb17	T	C	18: 37,619,629 (GRCm39)	I473T	probably damaging	Het
Pgbd5	T	A	8: 125,107,046 (GRCm39)	E165D	probably damaging	Het
Pgpep1l	A	T	7: 67,886,802 (GRCm39)	V169D	probably damaging	Het
Phf12	C	T	11: 77,900,312 (GRCm39)	T136I	probably benign	Het
Pif1	T	A	9: 65,495,132 (GRCm39)	M14K	probably benign	Het
Pigr	A	G	1: 130,772,823 (GRCm39)	E347G	probably damaging	Het
Plekha3	G	A	2: 76,513,223 (GRCm39)	E103K	possibly damaging	Het
Ptgs2	A	G	1: 149,980,150 (GRCm39)	I363V	probably damaging	Het
Rasl11a	T	A	5: 146,783,805 (GRCm39)		probably null	Het
Recql	T	C	6: 142,310,298 (GRCm39)	T511A	probably damaging	Het
Rgl2	T	A	17: 34,156,197 (GRCm39)		probably null	Het
Rpp25l	T	C	4: 41,712,763 (GRCm39)	Y4C	probably damaging	Het
Sass6	T	G	3: 116,401,126 (GRCm39)	C156G	probably damaging	Het
Sgta	T	G	10: 80,882,111 (GRCm39)	N288T	probably damaging	Het
Slco1a4	T	A	6: 141,770,771 (GRCm39)	T282S	probably benign	Het
Sox8	C	T	17: 25,786,915 (GRCm39)	V263M	probably damaging	Het
Sp8	A	G	12: 118,813,552 (GRCm39)	H469R	probably benign	Het
Spata1	A	T	3: 146,175,378 (GRCm39)		probably null	Het
Taar7a	G	A	10: 23,869,117 (GRCm39)	S88F	probably damaging	Het
Tnks2	T	C	19: 36,853,661 (GRCm39)	L749S	probably damaging	Het
Tollip	C	A	7: 141,446,592 (GRCm39)	R19L	probably damaging	Het
Tox2	G	A	2: 163,067,446 (GRCm39)	R55H	probably benign	Het
Vmn2r27	T	C	6: 124,177,636 (GRCm39)	E456G	possibly damaging	Het
Vmn2r77	T	A	7: 86,444,543 (GRCm39)	N65K	probably benign	Het
Vwf	T	C	6: 125,644,513 (GRCm39)	M2456T	probably benign	Het
Zfp526	A	G	7: 24,923,939 (GRCm39)	N66S	possibly damaging	Het
Zic1	T	C	9: 91,243,629 (GRCm39)	Y446C	probably damaging	Het

Other mutations in Smad4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01012:Smad4	APN	18	73,808,880 (GRCm39)	missense	probably damaging	1.00
IGL01647:Smad4	APN	18	73,773,544 (GRCm39)	splice site	probably benign
IGL02055:Smad4	APN	18	73,774,999 (GRCm39)	splice site	probably benign
IGL02101:Smad4	APN	18	73,791,723 (GRCm39)	missense	probably benign	0.02
IGL02306:Smad4	APN	18	73,795,940 (GRCm39)	critical splice acceptor site	probably null
R0391:Smad4	UTSW	18	73,791,720 (GRCm39)	missense	probably benign
R1118:Smad4	UTSW	18	73,773,333 (GRCm39)	missense	probably benign	0.41
R1163:Smad4	UTSW	18	73,781,978 (GRCm39)	missense	probably damaging	0.99
R1211:Smad4	UTSW	18	73,782,982 (GRCm39)	critical splice acceptor site	probably null
R1616:Smad4	UTSW	18	73,773,333 (GRCm39)	missense	probably benign	0.41
R1829:Smad4	UTSW	18	73,774,965 (GRCm39)	missense	probably benign	0.20
R2045:Smad4	UTSW	18	73,782,877 (GRCm39)	nonsense	probably null
R2126:Smad4	UTSW	18	73,795,815 (GRCm39)	missense	probably benign	0.02
R3013:Smad4	UTSW	18	73,781,975 (GRCm39)	missense	probably damaging	1.00
R3973:Smad4	UTSW	18	73,810,807 (GRCm39)	missense	possibly damaging	0.49
R3974:Smad4	UTSW	18	73,810,807 (GRCm39)	missense	possibly damaging	0.49
R3975:Smad4	UTSW	18	73,810,807 (GRCm39)	missense	possibly damaging	0.49
R4879:Smad4	UTSW	18	73,774,974 (GRCm39)	missense	probably damaging	1.00
R5101:Smad4	UTSW	18	73,808,931 (GRCm39)	missense	probably benign	0.41
R5597:Smad4	UTSW	18	73,795,898 (GRCm39)	missense	probably benign
R5984:Smad4	UTSW	18	73,810,982 (GRCm39)	start codon destroyed	probably benign	0.29
R6450:Smad4	UTSW	18	73,810,817 (GRCm39)	missense	possibly damaging	0.73
R7450:Smad4	UTSW	18	73,810,924 (GRCm39)	missense	probably damaging	1.00
R7524:Smad4	UTSW	18	73,808,942 (GRCm39)	missense	probably damaging	1.00
R8001:Smad4	UTSW	18	73,774,881 (GRCm39)	missense	probably damaging	0.99
R8526:Smad4	UTSW	18	73,790,330 (GRCm39)	splice site	probably null
R9110:Smad4	UTSW	18	73,782,941 (GRCm39)	missense	probably damaging	1.00
R9151:Smad4	UTSW	18	73,782,806 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CCGTTTCACTGAAAATGCCTAACTCTTG -3'
(R):5'- GGTAAACTTTAcctccatagcctctcca -3'

Sequencing Primer
(F):5'- ggaactggaggaagcagg -3'
(R):5'- ttctttctcccctccccc -3'

Posted On

2014-05-23