Mutagenetix > Incidental Mutation

Incidental Mutation 'R0564:Sh2d3c'

46048

Institutional Source

Beutler Lab

Gene Symbol

Sh2d3c

Ensembl Gene

ENSMUSG00000059013

Gene Name

SH2 domain containing 3C

Synonyms

Chat, Cas/HEF1-associated signal transducer, Nsp3, Shep1, SH2-containing Eph receptor-binding protein 1

MMRRC Submission

038755-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0564 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

32721055-32755512 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 32753052 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Cysteine to Tyrosine at position 749 (C749Y)

Ref Sequence

ENSEMBL: ENSMUSP00000073866 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000009707] [ENSMUST00000074248] [ENSMUST00000091059] [ENSMUST00000113242] [ENSMUST00000156617] [ENSMUST00000175763] [ENSMUST00000177382]

AlphaFold

Q9QZS8

Predicted Effect

probably benign
Transcript: ENSMUST00000009707

SMART Domains

Protein: ENSMUSP00000009707
Gene: ENSMUSG00000009563

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC
Pfam:Torsin	35	160	1.2e-54	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000074248
AA Change: C749Y

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000073866
Gene: ENSMUSG00000059013
AA Change: C749Y

Domain	Start	End	E-Value	Type
low complexity region	11	18	N/A	INTRINSIC
low complexity region	22	43	N/A	INTRINSIC
low complexity region	86	98	N/A	INTRINSIC
low complexity region	117	132	N/A	INTRINSIC
low complexity region	190	207	N/A	INTRINSIC
SH2	213	301	7.8e-21	SMART
low complexity region	333	348	N/A	INTRINSIC
low complexity region	400	415	N/A	INTRINSIC
low complexity region	422	436	N/A	INTRINSIC
low complexity region	474	487	N/A	INTRINSIC
RasGEF	576	849	8.18e-10	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000091059

SMART Domains

Protein: ENSMUSP00000088585
Gene: ENSMUSG00000039021

Domain	Start	End	E-Value	Type
TPR	75	108	2.26e-3	SMART
TPR	109	142	4.09e-1	SMART
TPR	150	183	8.3e-2	SMART
TPR	218	251	4.44e1	SMART
TPR	265	298	3.69e1	SMART
TPR	299	332	1.08e1	SMART
Blast:TPR	345	378	2e-10	BLAST
TPR	379	412	1.02e-1	SMART
TPR	420	453	7.27e0	SMART
Blast:TPR	454	487	2e-12	BLAST
low complexity region	631	644	N/A	INTRINSIC
low complexity region	666	679	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000113242
AA Change: C597Y

PolyPhen 2 Score 0.972 (Sensitivity: 0.77; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000108868
Gene: ENSMUSG00000059013
AA Change: C597Y

Domain	Start	End	E-Value	Type
low complexity region	38	55	N/A	INTRINSIC
SH2	61	149	7.8e-21	SMART
low complexity region	181	196	N/A	INTRINSIC
low complexity region	248	263	N/A	INTRINSIC
low complexity region	270	284	N/A	INTRINSIC
low complexity region	322	335	N/A	INTRINSIC
RasGEF	424	697	8.18e-10	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000123624

Predicted Effect

probably benign
Transcript: ENSMUST00000140999

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000149720

Predicted Effect

probably benign
Transcript: ENSMUST00000156617

SMART Domains

Protein: ENSMUSP00000122251
Gene: ENSMUSG00000009563

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000175763

SMART Domains

Protein: ENSMUSP00000135701
Gene: ENSMUSG00000009563

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000177382

SMART Domains

Protein: ENSMUSP00000134968
Gene: ENSMUSG00000009563

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC
Pfam:Torsin	35	101	1.4e-25	PFAM

Meta Mutation Damage Score

0.0747

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.7%
20x: 93.7%

Validation Efficiency

98% (52/53)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes an adaptor protein and member of a cytoplasmic protein family involved in cell migration. The encoded protein contains a putative Src homology 2 (SH2) domain and guanine nucleotide exchange factor-like domain which allows this signaling protein to form a complex with scaffolding protein Crk-associated substrate. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit neonatal lethality with absence of gastric milk. Surviving mice exhibit abnormal olfactory bulb innervation, fewer gonadotrophin positive cells in the hypothalamus, and decreased testes size. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 51 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adamtsl5	A	G	10: 80,344,847	V127A	probably damaging	Het
Alox12	T	A	11: 70,252,836	D202V	probably damaging	Het
Ankib1	A	G	5: 3,729,655	Y405H	probably damaging	Het
Apbb2	A	T	5: 66,452,250	M18K	probably damaging	Het
Atad2	C	A	15: 58,125,833		probably benign	Het
BC117090	A	T	16: 36,322,984	Y34*	probably null	Het
Birc6	T	A	17: 74,625,243		probably benign	Het
Ccdc126	T	C	6: 49,334,142	M28T	possibly damaging	Het
Cdc16	A	T	8: 13,781,618	D617V	probably damaging	Het
Cep135	G	A	5: 76,615,710	E516K	probably damaging	Het
Cep135	G	T	5: 76,638,949	M1081I	probably benign	Het
Col6a3	A	C	1: 90,807,734	V731G	probably damaging	Het
Cwc27	C	A	13: 104,661,357	E365*	probably null	Het
D230025D16Rik	T	A	8: 105,239,971		probably benign	Het
Dip2b	C	A	15: 100,162,719	Y258*	probably null	Het
Dnah17	A	G	11: 118,082,981	V1900A	probably damaging	Het
Dpysl2	A	T	14: 66,805,446		probably benign	Het
Dync2h1	A	T	9: 7,139,432	L1401Q	probably damaging	Het
Esf1	A	T	2: 140,158,586	Y427N	possibly damaging	Het
Fbln1	T	A	15: 85,227,107	V154D	probably benign	Het
Frem2	A	G	3: 53,656,109	F326L	probably damaging	Het
Gm4922	T	A	10: 18,784,065	N303I	possibly damaging	Het
Hist1h1t	G	T	13: 23,696,324	K153N	possibly damaging	Het
Iigp1	G	A	18: 60,390,451	V214M	probably damaging	Het
Luzp2	A	G	7: 54,835,962	K2E	probably damaging	Het
Mcc	A	G	18: 44,468,507	L410P	probably damaging	Het
Mfn2	A	G	4: 147,883,255	F452S	probably damaging	Het
Mib2	C	T	4: 155,659,460	G42S	probably damaging	Het
Micu2	A	G	14: 57,919,374	F335L	possibly damaging	Het
Mpp3	T	G	11: 102,005,347	K450T	possibly damaging	Het
Mtmr4	T	A	11: 87,598,888	V79E	probably damaging	Het
Nlrp4b	A	G	7: 10,714,658	I263V	probably benign	Het
Olfr551	T	C	7: 102,588,531	I71V	probably benign	Het
Olfr809	T	G	10: 129,776,136	V74G	probably damaging	Het
Pdk1	G	A	2: 71,880,039	W113*	probably null	Het
Phxr4	A	T	9: 13,431,697		probably benign	Het
Rad51ap2	T	A	12: 11,457,896	H606Q	probably benign	Het
Ralgapa1	A	T	12: 55,782,885	I187K	possibly damaging	Het
Rps27	A	G	3: 90,212,923		probably benign	Het
Sema3e	T	A	5: 14,236,085		probably null	Het
Siah2	T	C	3: 58,676,235	D210G	probably benign	Het
Smap2	G	A	4: 120,976,977	P155S	probably benign	Het
Snrk	C	T	9: 122,166,544	T463M	possibly damaging	Het
Tm9sf3	A	G	19: 41,245,525		probably benign	Het
Tmem132d	C	T	5: 127,784,778	E760K	probably damaging	Het
Tmem184c	A	T	8: 77,606,160		probably null	Het
Tmem235	A	T	11: 117,860,848	I33F	possibly damaging	Het
Tmem267	A	T	13: 119,492,639		probably null	Het
Top1	G	A	2: 160,714,265	R548Q	probably damaging	Het
Trio	T	C	15: 27,805,822	N527D	probably damaging	Het
Upf3a	A	G	8: 13,795,656	K252E	probably benign	Het

Other mutations in Sh2d3c

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01153:Sh2d3c	APN	2	32725084	missense	probably benign	0.00
IGL02326:Sh2d3c	APN	2	32749151	critical splice acceptor site	probably null
IGL03325:Sh2d3c	APN	2	32725258	missense	probably benign	0.00
R0008:Sh2d3c	UTSW	2	32753021	missense	probably damaging	1.00
R0619:Sh2d3c	UTSW	2	32753025	missense	probably damaging	1.00
R1138:Sh2d3c	UTSW	2	32749405	missense	probably benign	0.00
R1984:Sh2d3c	UTSW	2	32749244	nonsense	probably null
R3808:Sh2d3c	UTSW	2	32746096	missense	probably damaging	1.00
R4399:Sh2d3c	UTSW	2	32746160	missense	probably damaging	0.97
R4556:Sh2d3c	UTSW	2	32753009	missense	possibly damaging	0.81
R4840:Sh2d3c	UTSW	2	32721160	start codon destroyed	probably null	0.02
R5027:Sh2d3c	UTSW	2	32744802	missense	possibly damaging	0.95
R5367:Sh2d3c	UTSW	2	32745902	missense	probably damaging	1.00
R6754:Sh2d3c	UTSW	2	32754530	missense	probably damaging	1.00
R6916:Sh2d3c	UTSW	2	32752653	nonsense	probably null
R7029:Sh2d3c	UTSW	2	32754569	makesense	probably null
R7047:Sh2d3c	UTSW	2	32721160	start codon destroyed	probably null	0.02
R7636:Sh2d3c	UTSW	2	32725011	missense	probably benign	0.17
R7893:Sh2d3c	UTSW	2	32749376	nonsense	probably null
R8072:Sh2d3c	UTSW	2	32753138	missense	probably damaging	1.00
R8115:Sh2d3c	UTSW	2	32725264	missense	probably benign	0.12
R8447:Sh2d3c	UTSW	2	32752659	missense	probably damaging	1.00
R8553:Sh2d3c	UTSW	2	32745913	missense	probably damaging	1.00
R9133:Sh2d3c	UTSW	2	32744766	missense	possibly damaging	0.46
R9475:Sh2d3c	UTSW	2	32753027	missense	probably damaging	1.00
R9710:Sh2d3c	UTSW	2	32745877	nonsense	probably null

Predicted Primers

PCR Primer
(F):5'- AAGCCTTTCCTCAAGAGCCTGAAC -3'
(R):5'- AGCTACTCACCTTGCAGCTTGACC -3'

Sequencing Primer
(F):5'- CTATGGGTTCCCAAAGACTTCTGAG -3'
(R):5'- TGCAGCTTGACCTCAGC -3'

Posted On

2013-06-11