Mutagenetix > Incidental Mutation

Incidental Mutation 'R6567:Sos1'

522784

Institutional Source

Beutler Lab

Gene Symbol

Sos1

Ensembl Gene

ENSMUSG00000024241

Gene Name

SOS Ras/Rac guanine nucleotide exchange factor 1

Synonyms

4430401P03Rik

MMRRC Submission

044691-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6567 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

80701181-80787882 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 80740932 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Asparagine at position 618 (Y618N)

Ref Sequence

ENSEMBL: ENSMUSP00000067786 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000068714]

AlphaFold

Q62245

PDB Structure

CRK SH3 DOMAIN COMPLEXED WITH PEPTOID INHIBITOR [X-RAY DIFFRACTION]
SOLUTION NMR STRUCTURE OF THE GRB2 N-TERMINAL SH3 DOMAIN COMPLEXED WITH A TEN-RESIDUE PEPTIDE DERIVED FROM SOS DIRECT REFINEMENT AGAINST NOES, J-COUPLINGS, AND 1H AND 13C CHEMICAL SHIFTS, MINIMIZED AVERAGE STRUCTURE [SOLUTION NMR]
PLECKSTRIN HOMOLOGY DOMAIN OF SON OF SEVENLESS 1 (SOS1) WITH GLYCINE-SERINE ADDED TO THE N-TERMINUS, NMR, 20 STRUCTURES [SOLUTION NMR]
SOLUTION NMR STRUCTURE OF THE GRB2 N-TERMINAL SH3 DOMAIN COMPLEXED WITH A TEN-RESIDUE PEPTIDE DERIVED FROM SOS DIRECT REFINEMENT AGAINST NOES, J-COUPLINGS, AND 1H AND 13C CHEMICAL SHIFTS, 15 STRUCTURES [SOLUTION NMR]
SOLUTION NMR STRUCTURE OF THE GRB2 N-TERMINAL SH3 DOMAIN COMPLEXED WITH A TEN-RESIDUE PEPTIDE DERIVED FROM SOS DIRECT REFINEMENT AGAINST NOES, J-COUPLINGS, AND 1H AND 13C CHEMICAL SHIFTS, MINIMIZED AVERAGE STRUCTURE [SOLUTION NMR]
SOLUTION NMR STRUCTURE OF THE GRB2 N-TERMINAL SH3 DOMAIN COMPLEXED WITH A TEN-RESIDUE PEPTIDE DERIVED FROM SOS DIRECT REFINEMENT AGAINST NOES, J-COUPLINGS, AND 1H AND 13C CHEMICAL SHIFTS, 15 STRUCTURES [SOLUTION NMR]

Predicted Effect

probably damaging
Transcript: ENSMUST00000068714
AA Change: Y618N

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

SMART Domains

Protein: ENSMUSP00000067786
Gene: ENSMUSG00000024241
AA Change: Y618N

Domain	Start	End	E-Value	Type
Pfam:Histone	40	169	6.8e-16	PFAM
RhoGEF	204	389	8.5e-35	SMART
PH	444	548	2.44e-17	SMART
RasGEFN	596	741	2.18e-56	SMART
RasGEF	776	1020	4.44e-102	SMART
low complexity region	1079	1093	N/A	INTRINSIC
low complexity region	1116	1127	N/A	INTRINSIC
low complexity region	1132	1154	N/A	INTRINSIC
Blast:RasGEF	1155	1306	1e-51	BLAST

Meta Mutation Damage Score

0.6446

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.4%
20x: 98.0%

Validation Efficiency

100% (32/32)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein that is a guanine nucleotide exchange factor for RAS proteins, membrane proteins that bind guanine nucleotides and participate in signal transduction pathways. GTP binding activates and GTP hydrolysis inactivates RAS proteins. The product of this gene may regulate RAS proteins by facilitating the exchange of GTP for GDP. Mutations in this gene are associated with gingival fibromatosis 1 and Noonan syndrome type 4. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous null mutant embryos exhibit placental and cardiovascular defects resulting in death around mid-gestation. When heterozygous, these mutations enhance the eye defects of homozygous mutants of the epidermal growth factor receptor gene. [provided by MGI curators]

Allele List at MGI

All alleles(25) : Targeted, knock-out(2) Targeted, other(2) Gene trapped(21)

Other mutations in this stock

Total: 31 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
9930111J21Rik1	T	C	11: 48,838,950 (GRCm39)	T546A	probably benign	Het
Ahnak	G	T	19: 8,986,170 (GRCm39)	V2485L	probably benign	Het
C2cd5	T	C	6: 142,976,974 (GRCm39)	I722M	possibly damaging	Het
Clca4b	A	G	3: 144,638,100 (GRCm39)	I54T	possibly damaging	Het
Dennd2c	C	T	3: 103,039,335 (GRCm39)	A161V	probably benign	Het
Dmxl1	T	C	18: 49,992,246 (GRCm39)	Y331H	probably damaging	Het
Dnaaf11	C	T	15: 66,310,228 (GRCm39)	V347I	probably benign	Het
Dnajc2	G	A	5: 21,971,676 (GRCm39)	R247W	probably damaging	Het
Dock3	T	C	9: 106,773,946 (GRCm39)	T380A	probably benign	Het
Evc2	T	C	5: 37,576,508 (GRCm39)	V1044A	probably benign	Het
Ints2	T	C	11: 86,117,487 (GRCm39)	H745R	probably benign	Het
Kcnh1	T	A	1: 191,959,412 (GRCm39)	M322K	probably benign	Het
Mmp19	A	G	10: 128,632,275 (GRCm39)	T191A	probably benign	Het
Mms19	A	G	19: 41,938,206 (GRCm39)		probably null	Het
Mtcl3	G	T	10: 29,023,279 (GRCm39)	V209F	probably benign	Het
Ncapd3	T	C	9: 26,978,300 (GRCm39)	I833T	possibly damaging	Het
Nif3l1	T	A	1: 58,494,789 (GRCm39)	C253S	probably benign	Het
Or52e2	A	T	7: 102,804,135 (GRCm39)	I273K	possibly damaging	Het
Pate5	T	A	9: 35,750,411 (GRCm39)	Y87F	probably benign	Het
Pcsk1	T	A	13: 75,278,189 (GRCm39)	I584N	probably damaging	Het
Pms2	T	C	5: 143,865,786 (GRCm39)	V50A	probably damaging	Het
Rptor	A	G	11: 119,786,838 (GRCm39)	I1268V	probably benign	Het
Scap	C	T	9: 110,212,630 (GRCm39)	R1021W	probably damaging	Het
Tesk2	C	T	4: 116,649,361 (GRCm39)	A157V	probably damaging	Het
Tm6sf2	C	A	8: 70,528,174 (GRCm39)	H108N	probably damaging	Het
Trank1	T	C	9: 111,176,589 (GRCm39)	V287A	probably benign	Het
Tsks	A	T	7: 44,603,305 (GRCm39)	Q369L	probably damaging	Het
Vmn2r58	T	C	7: 41,514,673 (GRCm39)	T99A	probably benign	Het
Wbp11	C	T	6: 136,797,537 (GRCm39)	S294N	probably benign	Het
Zfp608	T	C	18: 55,030,628 (GRCm39)	Y1104C	probably damaging	Het
Zfp759	T	A	13: 67,287,150 (GRCm39)	S234T	probably benign	Het

Other mutations in Sos1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00805:Sos1	APN	17	80,705,953 (GRCm39)	missense	possibly damaging	0.94
IGL00915:Sos1	APN	17	80,741,367 (GRCm39)	missense	probably benign	0.00
IGL00929:Sos1	APN	17	80,716,025 (GRCm39)	missense	probably damaging	1.00
IGL01073:Sos1	APN	17	80,730,176 (GRCm39)	missense	probably damaging	1.00
IGL01116:Sos1	APN	17	80,752,929 (GRCm39)	missense	probably damaging	1.00
IGL01533:Sos1	APN	17	80,722,511 (GRCm39)	missense	probably damaging	0.97
IGL01546:Sos1	APN	17	80,716,040 (GRCm39)	missense	probably damaging	1.00
IGL01583:Sos1	APN	17	80,741,329 (GRCm39)	missense	probably benign	0.11
IGL01628:Sos1	APN	17	80,730,106 (GRCm39)	splice site	probably benign
IGL01837:Sos1	APN	17	80,730,157 (GRCm39)	missense	probably damaging	1.00
IGL02170:Sos1	APN	17	80,705,719 (GRCm39)	missense	probably damaging	0.99
IGL02426:Sos1	APN	17	80,742,372 (GRCm39)	missense	possibly damaging	0.82
IGL02992:Sos1	APN	17	80,726,445 (GRCm39)	missense	probably benign	0.01
IGL03037:Sos1	APN	17	80,727,758 (GRCm39)	missense	probably damaging	0.98
1mM(1):Sos1	UTSW	17	80,762,486 (GRCm39)	missense	possibly damaging	0.46
BB007:Sos1	UTSW	17	80,714,267 (GRCm39)	missense	probably benign	0.00
BB017:Sos1	UTSW	17	80,714,267 (GRCm39)	missense	probably benign	0.00
PIT4354001:Sos1	UTSW	17	80,756,785 (GRCm39)	missense	possibly damaging	0.52
R0056:Sos1	UTSW	17	80,721,050 (GRCm39)	missense	probably damaging	1.00
R0348:Sos1	UTSW	17	80,715,740 (GRCm39)	missense	probably benign
R0373:Sos1	UTSW	17	80,761,192 (GRCm39)	missense	probably damaging	1.00
R0477:Sos1	UTSW	17	80,742,363 (GRCm39)	missense	possibly damaging	0.92
R0621:Sos1	UTSW	17	80,759,408 (GRCm39)	critical splice donor site	probably null
R0839:Sos1	UTSW	17	80,741,159 (GRCm39)	missense	probably damaging	1.00
R1174:Sos1	UTSW	17	80,753,037 (GRCm39)	nonsense	probably null
R1490:Sos1	UTSW	17	80,721,104 (GRCm39)	missense	probably benign	0.11
R1566:Sos1	UTSW	17	80,761,345 (GRCm39)	missense	probably damaging	0.99
R1635:Sos1	UTSW	17	80,730,108 (GRCm39)	splice site	probably null
R3412:Sos1	UTSW	17	80,714,146 (GRCm39)	missense	probably benign
R3770:Sos1	UTSW	17	80,705,737 (GRCm39)	missense	probably damaging	0.97
R3951:Sos1	UTSW	17	80,731,610 (GRCm39)	missense	probably damaging	1.00
R3964:Sos1	UTSW	17	80,762,608 (GRCm39)	missense	probably damaging	1.00
R3966:Sos1	UTSW	17	80,762,608 (GRCm39)	missense	probably damaging	1.00
R4086:Sos1	UTSW	17	80,756,781 (GRCm39)	missense	probably benign	0.06
R4087:Sos1	UTSW	17	80,756,781 (GRCm39)	missense	probably benign	0.06
R4089:Sos1	UTSW	17	80,756,781 (GRCm39)	missense	probably benign	0.06
R4194:Sos1	UTSW	17	80,706,013 (GRCm39)	missense	probably benign	0.02
R4468:Sos1	UTSW	17	80,761,240 (GRCm39)	missense	probably damaging	1.00
R4469:Sos1	UTSW	17	80,761,240 (GRCm39)	missense	probably damaging	1.00
R4597:Sos1	UTSW	17	80,741,255 (GRCm39)	missense	probably benign	0.05
R4773:Sos1	UTSW	17	80,705,660 (GRCm39)	missense	probably damaging	0.99
R4923:Sos1	UTSW	17	80,742,381 (GRCm39)	missense	probably benign	0.10
R5120:Sos1	UTSW	17	80,715,677 (GRCm39)	missense	probably damaging	0.98
R5478:Sos1	UTSW	17	80,741,276 (GRCm39)	missense	probably damaging	1.00
R5566:Sos1	UTSW	17	80,761,319 (GRCm39)	missense	possibly damaging	0.91
R5984:Sos1	UTSW	17	80,759,561 (GRCm39)	missense	possibly damaging	0.68
R6053:Sos1	UTSW	17	80,722,463 (GRCm39)	missense	possibly damaging	0.94
R6153:Sos1	UTSW	17	80,756,764 (GRCm39)	missense	probably benign	0.01
R7392:Sos1	UTSW	17	80,731,629 (GRCm39)	missense	probably damaging	1.00
R7623:Sos1	UTSW	17	80,787,323 (GRCm39)	missense	probably benign	0.28
R7763:Sos1	UTSW	17	80,721,142 (GRCm39)	missense	probably benign
R7930:Sos1	UTSW	17	80,714,267 (GRCm39)	missense	probably benign	0.00
R8132:Sos1	UTSW	17	80,716,031 (GRCm39)	missense	probably damaging	1.00
R8236:Sos1	UTSW	17	80,715,712 (GRCm39)	missense	probably benign	0.41
R8322:Sos1	UTSW	17	80,715,728 (GRCm39)	missense	probably damaging	0.96
R8348:Sos1	UTSW	17	80,741,548 (GRCm39)	missense	probably benign	0.00
R8448:Sos1	UTSW	17	80,741,548 (GRCm39)	missense	probably benign	0.00
R8554:Sos1	UTSW	17	80,705,842 (GRCm39)	missense	probably damaging	0.99
R8850:Sos1	UTSW	17	80,741,405 (GRCm39)	missense	probably damaging	1.00
R8966:Sos1	UTSW	17	80,705,879 (GRCm39)	missense	possibly damaging	0.87
R9051:Sos1	UTSW	17	80,715,723 (GRCm39)	missense	probably benign
R9355:Sos1	UTSW	17	80,722,479 (GRCm39)	missense	possibly damaging	0.71
R9378:Sos1	UTSW	17	80,761,239 (GRCm39)	missense	probably damaging	1.00
R9576:Sos1	UTSW	17	80,742,367 (GRCm39)	missense	probably benign	0.11
X0020:Sos1	UTSW	17	80,756,706 (GRCm39)	missense	probably damaging	1.00
Z1177:Sos1	UTSW	17	80,761,347 (GRCm39)	missense	probably benign	0.05

Predicted Primers

PCR Primer
(F):5'- AGACAAGTGACCGTTTCTCTTTG -3'
(R):5'- TCTTTGCAGTACCGCAGCAC -3'

Sequencing Primer
(F):5'- AGTGACCGTTTCTCTTTGTAAATATG -3'
(R):5'- ATGCTGGACGTAACGGTGC -3'

Posted On

2018-06-06