Mutagenetix > Incidental Mutation

Incidental Mutation 'R3975:Smad4'

312623

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

040939-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R3975 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

73772080-73836851 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 73810807 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Lysine at position 59 (T59K)

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: T59K

PolyPhen 2 Score 0.494 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000025393
Gene: ENSMUSG00000024515
AA Change: T59K

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: T59K

PolyPhen 2 Score 0.494 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000110589
Gene: ENSMUSG00000024515
AA Change: T59K

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

0.3351

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.9%
20x: 93.6%

Validation Efficiency

95% (59/62)

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: 59 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam23	T	A	1: 63,586,888 (GRCm39)	Y416*	probably null	Het
Akr1b10	G	T	6: 34,369,431 (GRCm39)		probably null	Het
Arap2	G	T	5: 62,906,237 (GRCm39)	P261T	possibly damaging	Het
Bckdha	C	A	7: 25,330,858 (GRCm39)	D53Y	probably damaging	Het
Bfsp2	A	G	9: 103,357,271 (GRCm39)	V52A	probably benign	Het
Bola3	T	C	6: 83,328,249 (GRCm39)	L45P	probably benign	Het
Cacna2d4	A	G	6: 119,255,134 (GRCm39)		probably null	Het
Ccn6	C	G	10: 39,031,094 (GRCm39)	C143S	probably damaging	Het
Ceacam16	C	A	7: 19,587,537 (GRCm39)	Q410H	probably damaging	Het
Cenpe	A	G	3: 134,940,986 (GRCm39)		probably null	Het
Cenpe	T	C	3: 134,944,233 (GRCm39)		probably null	Het
Clca3a1	A	T	3: 144,738,400 (GRCm39)	V36D	probably damaging	Het
Copa	T	A	1: 171,948,812 (GRCm39)	S1155T	probably benign	Het
Crb2	C	A	2: 37,683,680 (GRCm39)	P1061T	possibly damaging	Het
Crot	T	C	5: 9,027,541 (GRCm39)	T264A	probably benign	Het
Cyp51	C	T	5: 4,141,877 (GRCm39)	G346S	probably damaging	Het
Dnah6	A	G	6: 73,098,975 (GRCm39)	S2027P	possibly damaging	Het
Fbh1	T	C	2: 11,772,021 (GRCm39)	H220R	possibly damaging	Het
Gdf2	T	A	14: 33,666,791 (GRCm39)	V171D	probably damaging	Het
Golgb1	T	G	16: 36,738,933 (GRCm39)	V2424G	probably damaging	Het
Gpbp1l1	T	C	4: 116,428,182 (GRCm39)		probably null	Het
Gpx6	C	A	13: 21,501,828 (GRCm39)	S150Y	probably damaging	Het
Greb1l	A	G	18: 10,522,247 (GRCm39)	N672S	possibly damaging	Het
Kcnma1	C	T	14: 24,053,815 (GRCm39)		probably null	Het
Lrba	T	C	3: 86,258,562 (GRCm39)	F1350L	probably damaging	Het
Nat8f4	A	G	6: 85,878,052 (GRCm39)	V157A	possibly damaging	Het
Niban1	T	C	1: 151,525,086 (GRCm39)	Y164H	probably damaging	Het
Nt5dc2	T	C	14: 30,860,832 (GRCm39)	S439P	probably damaging	Het
Or2ag12	T	C	7: 106,276,992 (GRCm39)	R234G	probably damaging	Het
Or2n1	A	G	17: 38,486,386 (GRCm39)	N137S	probably benign	Het
Or5t18	G	A	2: 86,636,804 (GRCm39)	P180S	possibly damaging	Het
Or8k40	T	A	2: 86,584,887 (GRCm39)	H65L	probably damaging	Het
Orm3	A	T	4: 63,274,395 (GRCm39)		probably null	Het
Otof	A	G	5: 30,528,056 (GRCm39)	L1929P	probably damaging	Het
Pex5l	C	A	3: 33,069,164 (GRCm39)	C111F	probably damaging	Het
Plcl1	T	A	1: 55,737,374 (GRCm39)	M905K	probably benign	Het
Prdm6	T	C	18: 53,673,278 (GRCm39)	I186T	possibly damaging	Het
Rara	T	G	11: 98,861,395 (GRCm39)	I236S	probably damaging	Het
Reln	A	T	5: 22,200,364 (GRCm39)	S1379T	possibly damaging	Het
Rnps1-ps	A	T	6: 7,983,149 (GRCm39)		noncoding transcript	Het
Rp1l1	T	A	14: 64,267,758 (GRCm39)	Y1115N	probably damaging	Het
Rpe65	A	T	3: 159,310,222 (GRCm39)	N135I	probably damaging	Het
Rps6	A	G	4: 86,775,050 (GRCm39)	V18A	probably benign	Het
Scrn3	T	C	2: 73,166,121 (GRCm39)	S385P	possibly damaging	Het
Sis	T	C	3: 72,850,968 (GRCm39)	T577A	probably damaging	Het
Slx1b	G	A	7: 126,290,979 (GRCm39)	L239F	probably damaging	Het
Smad6	A	G	9: 63,928,212 (GRCm39)	V32A	probably benign	Het
Smc6	T	A	12: 11,324,075 (GRCm39)	F73L	probably damaging	Het
Sorbs2	T	C	8: 46,225,747 (GRCm39)		probably null	Het
Svbp	T	A	4: 119,053,090 (GRCm39)	F32I	probably benign	Het
Tap1	C	A	17: 34,408,541 (GRCm39)		probably benign	Het
Tesk1	C	T	4: 43,445,786 (GRCm39)	P280S	possibly damaging	Het
Thrb	A	G	14: 18,033,456 (GRCm38)	I406M	probably damaging	Het
Tsc22d1	T	C	14: 76,656,049 (GRCm39)	S761P	probably damaging	Het
Ttn	T	C	2: 76,706,997 (GRCm39)		probably benign	Het
Umodl1	C	A	17: 31,203,763 (GRCm39)	Y525*	probably null	Het
Vmn2r70	C	T	7: 85,208,540 (GRCm39)	V646I	probably benign	Het
Wipf1	C	T	2: 73,267,513 (GRCm39)	G295D	probably benign	Het
Zim1	A	T	7: 6,680,129 (GRCm39)	H511Q	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
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'- TGGGAATGCTCTCTTCTCGC -3'
(R):5'- TGGTTTTCACTGCCTTCAAAAG -3'

Sequencing Primer
(F):5'- GCCTCTTTCAGTATCTGTACACAC -3'
(R):5'- TGCCTTCAAAAGATCAAAATTACTCC -3'

Posted On

2015-04-30