Mutagenetix > Incidental Mutations

Incidental Mutation 'R7524:Smad4'

582886

Institutional Source

Beutler Lab

Gene Symbol

Smad4

Ensembl Gene

ENSMUSG00000024515

Gene Name

SMAD family member 4

Synonyms

Dpc4, Smad 4, Madh4, DPC4, D18Wsu70e

MMRRC Submission

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R7524 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

73639009-73703780 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 73675871 bp

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Aspartic acid at position 108 (E108D)

Ref Sequence

ENSEMBL: ENSMUSP00000025393 (fasta)

Gene Model

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

PDB Structure

Structural basis for DNA recognition by constitutive Smad4 MH1 dimers [X-RAY DIFFRACTION]

Predicted Effect

probably damaging
Transcript: ENSMUST00000025393
AA Change: E108D

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

SMART Domains

Protein: ENSMUSP00000025393
Gene: ENSMUSG00000024515
AA Change: E108D

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: E108D

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

SMART Domains

Protein: ENSMUSP00000110589
Gene: ENSMUSG00000024515
AA Change: E108D

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

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.0%

Validation Efficiency

100% (79/79)

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: 78 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam29	C	T	8: 55,872,360	C353Y	probably damaging	Het
Afap1l2	T	A	19: 56,918,111	E452V	probably damaging	Het
AI464131	C	A	4: 41,498,779	V284L	probably benign	Het
Ak6	A	G	13: 100,663,907	D45G	probably benign	Het
Arhgap17	G	A	7: 123,306,420	P334L	probably damaging	Het
Asns	G	T	6: 7,677,259		probably null	Het
Bend7	A	G	2: 4,799,980	T424A	probably benign	Het
Btbd2	C	T	10: 80,646,444	E241K	probably damaging	Het
Commd2	A	C	3: 57,650,148	L99W	probably damaging	Het
Cpne9	A	T	6: 113,302,064	D473V	probably damaging	Het
Cuzd1	A	T	7: 131,311,618	F423L	probably damaging	Het
Cyp2d9	T	C	15: 82,455,945	F390L	probably damaging	Het
Dcaf5	T	A	12: 80,376,696	Q234L	probably benign	Het
Dennd3	T	G	15: 73,524,246	Y201*	probably null	Het
Dnah17	T	C	11: 118,121,481	D485G	probably benign	Het
Dnah5	A	T	15: 28,297,066	T1469S	possibly damaging	Het
Dnah6	T	C	6: 73,118,099	D2167G	probably damaging	Het
Dst	T	C	1: 34,291,893	V4921A	possibly damaging	Het
Ephb2	A	G	4: 136,659,709	Y736H	probably damaging	Het
Eri2	C	G	7: 119,785,749	V510L	probably benign	Het
Eya2	G	A	2: 165,769,326		probably null	Het
Fam208a	T	A	14: 27,466,203	C869S	probably damaging	Het
Fastkd5	G	T	2: 130,616,128	Q181K	probably benign	Het
Fcgbp	T	C	7: 28,102,966	S1440P	probably damaging	Het
Fkbp9	G	A	6: 56,868,740	V354M	probably damaging	Het
Frmpd1	T	A	4: 45,271,181	S304T	probably benign	Het
Gtf2a2	T	A	9: 70,015,347	Y3*	probably null	Het
Hagh	G	A	17: 24,861,340	V226I	probably benign	Het
Hemk1	T	A	9: 107,328,285	I293F	probably benign	Het
Kcna3	A	G	3: 107,037,207	E262G	probably damaging	Het
Kcnt2	A	T	1: 140,584,055	T983S	probably damaging	Het
Klhdc3	A	T	17: 46,678,414	H7Q	probably damaging	Het
Knl1	A	T	2: 119,065,979	Q94L	probably damaging	Het
Krt12	T	C	11: 99,419,659	D224G	probably damaging	Het
Lats1	T	A	10: 7,701,978	S289T	possibly damaging	Het
Man2a2	G	C	7: 80,368,865	A82G	probably benign	Het
Map1a	G	A	2: 121,289,812	V60M	probably damaging	Het
Mms22l	T	A	4: 24,536,138	F536I	possibly damaging	Het
Ms4a14	T	C	19: 11,303,836	T453A	unknown	Het
Muc3a	A	C	5: 137,210,563	I151S	probably benign	Het
Oaf	G	A	9: 43,222,780	R215C	probably damaging	Het
Olfr1019	T	A	2: 85,841,357	M145L	probably benign	Het
Olfr1217	T	A	2: 89,023,971	I11L	probably benign	Het
Olfr1233	A	G	2: 89,339,877	C142R	probably benign	Het
Olfr1507	T	C	14: 52,490,293	I224V	probably damaging	Het
Olfr5	T	C	7: 6,480,587	N190D	probably benign	Het
Olfr8	T	A	10: 78,955,491	Y95*	probably null	Het
Pcdhgb4	A	T	18: 37,721,608	D352V	probably benign	Het
Pced1a	A	G	2: 130,422,028	F235L	probably benign	Het
Pclo	A	G	5: 14,678,303	I2392V	unknown	Het
Pld1	A	T	3: 28,024,321	D43V	possibly damaging	Het
Ppp1r1b	C	A	11: 98,350,894	A51D	possibly damaging	Het
Prr23a1	T	A	9: 98,842,864	L93H	probably damaging	Het
Psg20	T	C	7: 18,684,659	D61G	probably benign	Het
Rab40b	T	A	11: 121,388,052	I31F	probably damaging	Het
Rasd2	T	C	8: 75,222,081	F212L	probably benign	Het
Rbl2	A	G	8: 91,115,193	I1006V	probably benign	Het
Sema6c	A	G	3: 95,167,060	E59G	probably benign	Het
Slc22a2	G	T	17: 12,606,057	V269L	possibly damaging	Het
Slc2a1	C	T	4: 119,132,612	P149S	probably damaging	Het
Sorbs2	T	A	8: 45,795,656	I648K	probably benign	Het
Suclg1	A	T	6: 73,263,841	I118F	probably damaging	Het
Tet2	A	G	3: 133,480,229	I1149T	probably benign	Het
Tfr2	T	A	5: 137,571,489	Y82*	probably null	Het
Tfr2	G	T	5: 137,583,489	V613L	probably benign	Het
Tg	A	T	15: 66,696,161	M1305L	probably benign	Het
Tmem176a	A	T	6: 48,844,105	M170L	probably benign	Het
Trim71	T	C	9: 114,513,162	N684S	probably benign	Het
Tspan9	A	G	6: 127,965,251	I212T	probably benign	Het
Ttn	A	G	2: 76,942,975	V2361A	possibly damaging	Het
Uqcrc1	C	T	9: 108,936,759	T14M	possibly damaging	Het
Vmn2r11	T	C	5: 109,053,982	I219V	probably benign	Het
Vmn2r76	T	C	7: 86,225,369	H800R	probably benign	Het
Vmn2r76	C	T	7: 86,230,166	G309R	probably benign	Het
Xpc	A	T	6: 91,499,531	C529S	probably benign	Het
Zfp455	T	A	13: 67,207,624	S254T	possibly damaging	Het
Zfp746	T	C	6: 48,064,889	H301R	possibly damaging	Het
Zyg11a	A	T	4: 108,192,074	I490N	probably damaging	Het

Other mutations in Smad4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01012:Smad4	APN	18	73675809	missense	probably damaging	1.00
IGL01647:Smad4	APN	18	73640473	splice site	probably benign
IGL02055:Smad4	APN	18	73641928	splice site	probably benign
IGL02101:Smad4	APN	18	73658652	missense	probably benign	0.02
IGL02306:Smad4	APN	18	73662869	critical splice acceptor site	probably null
R0391:Smad4	UTSW	18	73658649	missense	probably benign
R1118:Smad4	UTSW	18	73640262	missense	probably benign	0.41
R1163:Smad4	UTSW	18	73648907	missense	probably damaging	0.99
R1211:Smad4	UTSW	18	73649911	critical splice acceptor site	probably null
R1616:Smad4	UTSW	18	73640262	missense	probably benign	0.41
R1742:Smad4	UTSW	18	73675897	missense	probably damaging	1.00
R1829:Smad4	UTSW	18	73641894	missense	probably benign	0.20
R2045:Smad4	UTSW	18	73649806	nonsense	probably null
R2126:Smad4	UTSW	18	73662744	missense	probably benign	0.02
R3013:Smad4	UTSW	18	73648904	missense	probably damaging	1.00
R3973:Smad4	UTSW	18	73677736	missense	possibly damaging	0.49
R3974:Smad4	UTSW	18	73677736	missense	possibly damaging	0.49
R3975:Smad4	UTSW	18	73677736	missense	possibly damaging	0.49
R4879:Smad4	UTSW	18	73641903	missense	probably damaging	1.00
R5101:Smad4	UTSW	18	73675860	missense	probably benign	0.41
R5597:Smad4	UTSW	18	73662827	missense	probably benign
R5984:Smad4	UTSW	18	73677911	start codon destroyed	probably benign	0.29
R6450:Smad4	UTSW	18	73677746	missense	possibly damaging	0.73
R7450:Smad4	UTSW	18	73677853	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CTTCATTTGAAGTCTTGAGTAGTCCTC -3'
(R):5'- GATGTTGGAGCAAAGCCGTG -3'

Sequencing Primer
(F):5'- GTCCTCAAGTACAAACTTTAAGTAGG -3'
(R):5'- CAAAGCCGTGTGTGCTCTG -3'

Posted On

2019-10-17