Mutagenetix > Incidental Mutation

Incidental Mutation 'R4879:Smad4'

375177

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

042488-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4879 (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 73774974 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Cysteine to Arginine at position 442 (C442R)

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: C442R

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

SMART Domains

Protein: ENSMUSP00000025393
Gene: ENSMUSG00000024515
AA Change: C442R

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: C442R

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

SMART Domains

Protein: ENSMUSP00000110589
Gene: ENSMUSG00000024515
AA Change: C442R

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: ENSMUST00000131339

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000142672

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000147315

Meta Mutation Damage Score

0.9600

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 97.0%
20x: 94.4%

Validation Efficiency

97% (86/89)

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
Abca6	T	A	11: 110,110,526 (GRCm39)	Y541F	probably damaging	Het
Acot12	T	A	13: 91,911,083 (GRCm39)	V136E	probably benign	Het
Aftph	A	G	11: 20,648,311 (GRCm39)		probably null	Het
Ambra1	C	T	2: 91,603,039 (GRCm39)		probably benign	Het
Anks6	C	T	4: 47,030,795 (GRCm39)	G601S	probably damaging	Het
Ano9	T	C	7: 140,690,415 (GRCm39)	D73G	probably benign	Het
Asap3	G	A	4: 135,969,975 (GRCm39)	D778N	probably benign	Het
Atp8a2	G	T	14: 60,245,918 (GRCm39)	Y591*	probably null	Het
Blk	T	C	14: 63,613,414 (GRCm39)	T365A	probably benign	Het
C4b	G	T	17: 34,962,621 (GRCm39)	S27Y	probably damaging	Het
C6	G	T	15: 4,833,129 (GRCm39)		probably null	Het
Ccdc33	T	A	9: 57,974,839 (GRCm39)	I345F	possibly damaging	Het
Cetn3	T	A	13: 81,940,268 (GRCm39)		probably benign	Het
Cntn3	T	A	6: 102,244,389 (GRCm39)	I387L	possibly damaging	Het
Cog8	A	G	8: 107,782,984 (GRCm39)	C102R	probably damaging	Het
Cspg4b	T	C	13: 113,456,321 (GRCm39)	I789T	probably benign	Het
Cyp2c55	CA	C	19: 39,030,522 (GRCm39)		probably null	Het
Defa40	T	A	8: 21,740,380 (GRCm39)	L62Q	probably damaging	Het
Dmxl1	C	T	18: 50,022,534 (GRCm39)	A1624V	probably damaging	Het
Dnah1	T	G	14: 31,022,705 (GRCm39)	E1144A	possibly damaging	Het
Dnah12	T	A	14: 26,439,201 (GRCm39)		probably null	Het
Dnah2	G	A	11: 69,367,517 (GRCm39)	T1794I	probably damaging	Het
Entrep1	T	C	19: 23,953,019 (GRCm39)		probably null	Het
Erbin	A	T	13: 103,971,282 (GRCm39)	M778K	probably benign	Het
Fbxw10	G	T	11: 62,738,573 (GRCm39)	A156S	probably damaging	Het
Flnc	T	A	6: 29,460,805 (GRCm39)	F2632Y	probably damaging	Het
Frmd4a	A	G	2: 4,534,628 (GRCm39)	K160E	probably damaging	Het
Glipr1l2	A	G	10: 111,943,029 (GRCm39)	K295E	probably benign	Het
Herc1	T	A	9: 66,370,119 (GRCm39)	C465*	probably null	Het
Hoxb4	A	G	11: 96,211,014 (GRCm39)	I205V	probably damaging	Het
Ikbke	GCC	G	1: 131,203,004 (GRCm39)		probably null	Het
Il36a	A	G	2: 24,106,032 (GRCm39)	N29S	probably benign	Het
Ilk	A	G	7: 105,391,011 (GRCm39)	S292G	probably benign	Het
Itgb5	G	C	16: 33,696,348 (GRCm39)	G180R	probably damaging	Het
Josd1-ps	T	C	7: 27,648,768 (GRCm39)		noncoding transcript	Het
Kcnip4	T	C	5: 48,567,207 (GRCm39)	D120G	possibly damaging	Het
Kin	A	G	2: 10,085,455 (GRCm39)	D5G	probably benign	Het
Lrrtm2	C	A	18: 35,346,372 (GRCm39)	G310V	probably damaging	Het
Med1	T	C	11: 98,046,186 (GRCm39)		probably benign	Het
Mepce	C	A	5: 137,783,544 (GRCm39)		probably benign	Het
Nckipsd	T	A	9: 108,691,114 (GRCm39)		probably benign	Het
Notch3	T	A	17: 32,366,937 (GRCm39)	Q866L	probably benign	Het
Or52b4	A	T	7: 102,183,962 (GRCm39)	T3S	probably benign	Het
Or5l14	A	T	2: 87,793,040 (GRCm39)	H65Q	possibly damaging	Het
Or8k20	A	T	2: 86,106,107 (GRCm39)	C241*	probably null	Het
Orai1	T	C	5: 123,149,894 (GRCm39)		probably benign	Het
Pate12	G	A	9: 36,344,089 (GRCm39)	C24Y	probably damaging	Het
Pcdhb8	A	T	18: 37,489,219 (GRCm39)	E299V	probably damaging	Het
Pcnx4	G	A	12: 72,613,959 (GRCm39)	D635N	probably damaging	Het
Pex5	T	C	6: 124,375,322 (GRCm39)	I567V	probably benign	Het
Ppfibp2	T	C	7: 107,328,390 (GRCm39)	S485P	probably benign	Het
Sbno1	T	C	5: 124,542,087 (GRCm39)	Y356C	probably damaging	Het
Sdcbp	T	C	4: 6,381,056 (GRCm39)	I67T	possibly damaging	Het
Slc5a7	A	G	17: 54,583,679 (GRCm39)	I537T	probably benign	Het
Slc66a1	A	T	4: 139,029,095 (GRCm39)		probably null	Het
Smpd5	A	G	15: 76,179,070 (GRCm39)	H146R	possibly damaging	Het
Snai2	A	G	16: 14,524,605 (GRCm39)	Y37C	probably benign	Het
Snapc4	C	T	2: 26,256,004 (GRCm39)	S840N	possibly damaging	Het
Stpg2	T	C	3: 138,921,134 (GRCm39)	I113T	probably benign	Het
Tbc1d32	T	C	10: 55,925,125 (GRCm39)		probably null	Het
Tfg	A	T	16: 56,521,520 (GRCm39)	S39R	probably damaging	Het
Thsd7b	T	A	1: 130,116,236 (GRCm39)	S1330T	possibly damaging	Het
Tnfaip3	T	C	10: 18,881,321 (GRCm39)	T322A	probably benign	Het
Tpra1	A	G	6: 88,888,691 (GRCm39)	Y291C	probably damaging	Het
Trcg1	A	G	9: 57,154,003 (GRCm39)	D658G	probably damaging	Het
Trip4	C	T	9: 65,782,304 (GRCm39)	V143I	probably benign	Het
Trp53bp1	T	C	2: 121,033,084 (GRCm39)	K1691E	probably damaging	Het
Ttc8	T	A	12: 98,908,562 (GRCm39)	M77K	possibly damaging	Het
Tubb2a	A	T	13: 34,258,572 (GRCm39)	M406K	probably benign	Het
Txnrd1	T	A	10: 82,717,751 (GRCm39)		probably null	Het
Ugt2a3	C	A	5: 87,479,144 (GRCm39)	R268L	probably benign	Het
Usp34	T	G	11: 23,323,410 (GRCm39)	M982R	possibly damaging	Het
Vmn2r43	T	A	7: 8,258,102 (GRCm39)	K370N	probably benign	Het
Vopp1	A	T	6: 57,739,355 (GRCm39)		probably benign	Het
Vps11	A	C	9: 44,264,597 (GRCm39)	C660G	probably benign	Het
Wnk1	T	C	6: 119,926,338 (GRCm39)	H1137R	probably damaging	Het
Wtap	A	G	17: 13,188,322 (GRCm39)	Y193H	probably damaging	Het
Zfp462	T	A	4: 55,009,444 (GRCm39)	V470D	probably benign	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
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'- CCGAGGTTACAAGTCACCAC -3'
(R):5'- CACGGATCTGTTCCAAACACTG -3'

Sequencing Primer
(F):5'- AGGTTACAAGTCACCACTGTACTCTG -3'
(R):5'- CCTGGGACTGCAGTTACATAGTTAC -3'

Posted On

2016-03-17