Mutagenetix > Incidental Mutation

Incidental Mutation 'R5101:Smad4'

392385

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

042852-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5101 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

73772080-73836851 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 73808931 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 112 (V112A)

Ref Sequence

ENSEMBL: ENSMUSP00000110589 (fasta)

Gene Model

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

AlphaFold

P97471

Predicted Effect

probably benign
Transcript: ENSMUST00000025393
AA Change: V112A

PolyPhen 2 Score 0.410 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000025393
Gene: ENSMUSG00000024515
AA Change: V112A

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 benign
Transcript: ENSMUST00000114939
AA Change: V112A

PolyPhen 2 Score 0.410 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000110589
Gene: ENSMUSG00000024515
AA Change: V112A

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

Meta Mutation Damage Score

0.4583

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.4%
20x: 93.0%

Validation Efficiency

100% (57/57)

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: 53 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam17	T	C	12: 21,423,406 (GRCm39)	T10A	possibly damaging	Het
Adgrg3	T	C	8: 95,763,563 (GRCm39)	F288S	probably benign	Het
Ago2	A	G	15: 72,991,339 (GRCm39)	V533A	probably damaging	Het
Akap9	T	G	5: 4,051,748 (GRCm39)	V1505G	probably damaging	Het
Apob	T	C	12: 8,061,934 (GRCm39)	I3439T	probably benign	Het
C1qtnf7	T	A	5: 43,773,314 (GRCm39)	Y204*	probably null	Het
Cdc42bpb	T	C	12: 111,265,549 (GRCm39)	E1461G	probably damaging	Het
Cdh3	C	T	8: 107,268,024 (GRCm39)	A353V	possibly damaging	Het
Clec4d	A	G	6: 123,244,071 (GRCm39)	Y60C	probably damaging	Het
Cmya5	T	A	13: 93,228,111 (GRCm39)	T2326S	possibly damaging	Het
Cnot1	G	A	8: 96,486,815 (GRCm39)	L631F	possibly damaging	Het
Cntnap5a	C	T	1: 116,370,026 (GRCm39)	T881I	probably benign	Het
Col6a1	T	A	10: 76,545,740 (GRCm39)	T911S	unknown	Het
Ctsw	A	G	19: 5,515,703 (GRCm39)	V287A	probably benign	Het
Cyp2c23	T	C	19: 44,017,622 (GRCm39)	E2G	unknown	Het
Cytip	A	T	2: 58,037,911 (GRCm39)	I151N	probably damaging	Het
Dnah10	A	G	5: 124,909,577 (GRCm39)	T4399A	possibly damaging	Het
Dock3	A	T	9: 106,846,980 (GRCm39)	I883N	probably damaging	Het
Entpd3	A	G	9: 120,395,608 (GRCm39)	*530W	probably null	Het
Gm4787	G	C	12: 81,424,604 (GRCm39)	T518S	probably benign	Het
Gp1ba	G	A	11: 70,532,225 (GRCm39)	V664M	probably benign	Het
Gpd2	T	A	2: 57,245,913 (GRCm39)	I481N	probably damaging	Het
Gvin-ps5	T	C	7: 105,929,096 (GRCm39)		noncoding transcript	Het
Ildr2	A	G	1: 166,135,331 (GRCm39)	D342G	probably damaging	Het
Krt87	A	G	15: 101,385,391 (GRCm39)	I327T	probably benign	Het
Lats1	T	A	10: 7,588,348 (GRCm39)	C988*	probably null	Het
Lpin2	G	A	17: 71,550,965 (GRCm39)	W708*	probably null	Het
Mast4	T	C	13: 102,872,864 (GRCm39)	D2168G	probably benign	Het
Myo6	G	T	9: 80,177,321 (GRCm39)	E606*	probably null	Het
Nek7	A	G	1: 138,443,431 (GRCm39)	V174A	probably benign	Het
Nid1	T	A	13: 13,658,339 (GRCm39)	C695S	probably damaging	Het
Nme8	A	G	13: 19,875,017 (GRCm39)		probably null	Het
Nr2c2	T	C	6: 92,131,497 (GRCm39)		probably null	Het
Or1e16	AGCGGTCGTAGGC	AGC	11: 73,286,480 (GRCm39)		probably null	Het
Or2ag18	A	T	7: 106,405,420 (GRCm39)	I83K	possibly damaging	Het
Or4x11	A	G	2: 89,867,391 (GRCm39)	M43V	probably benign	Het
Or51ab3	G	A	7: 103,201,150 (GRCm39)	E53K	probably damaging	Het
Or9g19	A	G	2: 85,600,268 (GRCm39)	N41S	probably damaging	Het
Pms2	A	G	5: 143,865,006 (GRCm39)	D696G	probably damaging	Het
Psapl1	T	A	5: 36,361,494 (GRCm39)	C29S	probably damaging	Het
Scn3a	A	T	2: 65,291,850 (GRCm39)	V1632D	probably damaging	Het
Slc22a1	C	T	17: 12,886,129 (GRCm39)	G168D	probably damaging	Het
Smc4	T	C	3: 68,935,845 (GRCm39)	V796A	probably benign	Het
Smco4	A	G	9: 15,455,968 (GRCm39)	E18G	unknown	Het
Spata31e2	T	C	1: 26,722,417 (GRCm39)	E921G	possibly damaging	Het
Sugp2	A	G	8: 70,713,139 (GRCm39)	E1035G	probably damaging	Het
Syde2	T	C	3: 145,721,393 (GRCm39)	S820P	probably damaging	Het
Syn2	T	C	6: 115,240,860 (GRCm39)	L410P	probably damaging	Het
Tmem131l	T	C	3: 83,844,811 (GRCm39)	N466S	probably damaging	Het
Uba1y	T	G	Y: 821,447 (GRCm39)		probably null	Het
Unc79	T	C	12: 103,078,769 (GRCm39)	S1645P	probably damaging	Het
Vmn2r17	A	T	5: 109,576,217 (GRCm39)	S363C	probably damaging	Het
Vmn2r78	T	C	7: 86,571,563 (GRCm39)	Y458H	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
R1742:Smad4	UTSW	18	73,808,968 (GRCm39)	missense	probably damaging	1.00
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
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'- CTTCATTTGAAGTCTTGAGTAGTCC -3'
(R):5'- ATGTTGGAGCAAAGCCGTG -3'

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

Posted On

2016-06-15