Mutagenetix > Incidental Mutation

Incidental Mutation 'R6450:Smad4'

519384

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

044586-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6450 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

73772080-73836851 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 73810817 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Threonine at position 56 (S56T)

Ref Sequence

ENSEMBL: ENSMUSP00000110589 (fasta)

Gene Model

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

AlphaFold

P97471

Predicted Effect

possibly damaging
Transcript: ENSMUST00000025393
AA Change: S56T

PolyPhen 2 Score 0.730 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000025393
Gene: ENSMUSG00000024515
AA Change: S56T

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

possibly damaging
Transcript: ENSMUST00000114939
AA Change: S56T

PolyPhen 2 Score 0.730 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000110589
Gene: ENSMUSG00000024515
AA Change: S56T

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

0.4484

Coding Region Coverage

1x: 100.0%
3x: 99.8%
10x: 98.5%
20x: 95.1%

Validation Efficiency

97% (68/70)

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: 71 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca14	C	G	7: 119,815,449 (GRCm39)	N232K	probably benign	Het
Acaca	T	A	11: 84,171,294 (GRCm39)	V5E	probably damaging	Het
Adam18	A	T	8: 25,119,691 (GRCm39)	D529E	probably benign	Het
Adgrb3	T	C	1: 25,459,683 (GRCm39)	T798A	probably benign	Het
Alyref	T	C	11: 120,486,872 (GRCm39)	T130A	probably benign	Het
Arhgap24	A	G	5: 103,044,990 (GRCm39)	S591G	probably benign	Het
Carmil1	C	T	13: 24,220,547 (GRCm39)	G655E	probably damaging	Het
Cdc42bpg	T	A	19: 6,364,518 (GRCm39)		probably null	Het
Clec12a	T	A	6: 129,330,366 (GRCm39)	L48H	probably damaging	Het
Coq2	C	A	5: 100,809,770 (GRCm39)		probably benign	Het
Crb2	C	A	2: 37,683,838 (GRCm39)	F1113L	possibly damaging	Het
Ctla4	A	T	1: 60,951,872 (GRCm39)	M134L	probably benign	Het
Dnase1l1	C	T	X: 73,320,644 (GRCm39)		probably null	Homo
Dync2i1	A	T	12: 116,210,347 (GRCm39)	Y314*	probably null	Het
Efhb	A	G	17: 53,759,632 (GRCm39)	V290A	possibly damaging	Het
Epha8	T	C	4: 136,659,210 (GRCm39)	N843S	probably damaging	Het
Eva1a	A	T	6: 82,069,086 (GRCm39)	I138F	probably damaging	Het
Fat2	T	A	11: 55,180,136 (GRCm39)	I1402F	probably damaging	Het
Fat3	A	T	9: 15,910,466 (GRCm39)	H1845Q	possibly damaging	Het
Gimap8	T	A	6: 48,633,385 (GRCm39)	F401L	probably benign	Het
Gpr162	C	T	6: 124,838,152 (GRCm39)	R166Q	possibly damaging	Het
H2ac8	A	G	13: 23,755,119 (GRCm39)	V55A	probably damaging	Het
Hdac4	G	A	1: 91,912,433 (GRCm39)	P348S	possibly damaging	Het
Hmcn2	T	C	2: 31,251,812 (GRCm39)	V849A	probably benign	Het
Inpp5b	T	A	4: 124,686,045 (GRCm39)	N696K	probably damaging	Het
Kdm5d	G	T	Y: 927,056 (GRCm39)	R598L	probably damaging	Homo
Kidins220	T	C	12: 25,107,190 (GRCm39)	S1548P	probably benign	Het
Kif2b	C	A	11: 91,467,192 (GRCm39)	V364L	probably damaging	Het
Kitl	A	G	10: 99,923,256 (GRCm39)	M1V	probably null	Het
Klra9	G	T	6: 130,155,995 (GRCm39)	Y253*	probably null	Het
Map6	T	C	7: 98,917,245 (GRCm39)	I6T	probably damaging	Het
Mastl	T	C	2: 23,010,941 (GRCm39)	T768A	probably damaging	Het
Mettl16	T	C	11: 74,696,164 (GRCm39)	V335A	probably benign	Het
Mpl	T	C	4: 118,305,897 (GRCm39)		probably null	Het
Myo5c	C	T	9: 75,193,860 (GRCm39)	T1205I	probably benign	Het
Nav2	C	A	7: 49,244,114 (GRCm39)	L2114I	probably damaging	Het
Neb	T	A	2: 52,084,481 (GRCm39)	K5330*	probably null	Het
Nfe2l1	C	T	11: 96,718,161 (GRCm39)	E125K	possibly damaging	Het
Onecut3	A	G	10: 80,331,922 (GRCm39)	K361E	probably damaging	Het
Or4f47	T	A	2: 111,972,725 (GRCm39)	L145*	probably null	Het
Osbpl6	A	G	2: 76,395,174 (GRCm39)	N370S	possibly damaging	Het
Otud4	T	A	8: 80,399,626 (GRCm39)	M780K	probably benign	Het
P2rx4	A	G	5: 122,865,304 (GRCm39)	T310A	possibly damaging	Het
Pcdha11	G	T	18: 37,146,215 (GRCm39)	D769Y	probably damaging	Het
Pcgf6	C	T	19: 47,037,527 (GRCm39)	R124H	probably benign	Het
Pibf1	T	A	14: 99,374,646 (GRCm39)	Y362N	probably damaging	Het
Ppm1g	T	C	5: 31,360,468 (GRCm39)	E422G	probably benign	Het
Prmt8	T	C	6: 127,709,606 (GRCm39)	I85V	possibly damaging	Het
Prss27	A	T	17: 24,263,988 (GRCm39)	K225*	probably null	Het
Rai1	A	T	11: 60,077,429 (GRCm39)	T498S	probably benign	Het
Sbf2	C	A	7: 110,062,070 (GRCm39)	G23V	probably damaging	Het
Sdha	C	T	13: 74,482,412 (GRCm39)		probably null	Het
Sgo2a	C	T	1: 58,042,092 (GRCm39)	Q140*	probably null	Het
Sh3rf3	A	G	10: 58,819,966 (GRCm39)	D259G	probably damaging	Het
Slc27a3	C	A	3: 90,292,777 (GRCm39)	D631Y	probably damaging	Het
Slc7a10	T	C	7: 34,886,015 (GRCm39)	S37P	possibly damaging	Het
Slco6d1	A	G	1: 98,349,192 (GRCm39)	T88A	probably benign	Het
Smarcd1	A	G	15: 99,605,766 (GRCm39)	I346V	possibly damaging	Het
Spast	C	T	17: 74,675,835 (GRCm39)	P260S	probably benign	Het
Spata31f1e	C	A	4: 42,792,489 (GRCm39)	G548W	probably damaging	Het
Sprr2i	A	T	3: 92,316,017 (GRCm39)		probably benign	Het
Sptbn5	A	G	2: 119,877,616 (GRCm39)		probably benign	Het
Taar9	A	T	10: 23,985,138 (GRCm39)	Y99N	probably damaging	Het
Trappc10	A	T	10: 78,045,284 (GRCm39)	M468K	possibly damaging	Het
Trim66	T	C	7: 109,059,945 (GRCm39)	R814G	probably benign	Het
Tspan31	A	G	10: 126,904,227 (GRCm39)	C157R	probably damaging	Het
Vmn2r90	A	G	17: 17,953,498 (GRCm39)	D554G	possibly damaging	Het
Vmn2r91	A	T	17: 18,305,527 (GRCm39)	D70V	probably damaging	Het
Wdfy4	C	T	14: 32,830,649 (GRCm39)	G928R	probably damaging	Het
Zfp346	G	T	13: 55,261,517 (GRCm39)	K102N	probably damaging	Het
Zmym4	G	A	4: 126,789,099 (GRCm39)	P1002S	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
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
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'- GTGGAGCTCACATTAAATTGGTAG -3'
(R):5'- CTTGCAACATTGGCCATTGG -3'

Sequencing Primer
(F):5'- GAAGTCGTCCATCCAATG -3'
(R):5'- GGTTTTCACTGCCTTCAAAAGATC -3'

Posted On

2018-05-24