Mutagenetix > Incidental Mutation

Incidental Mutation 'R5992:Cyld'

480894

Institutional Source

Beutler Lab

Gene Symbol

Cyld

Ensembl Gene

ENSMUSG00000036712

Gene Name

CYLD lysine 63 deubiquitinase

Synonyms

CYLD1, C130039D01Rik, 2900009M21Rik, 2010013M14Rik

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R5992 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

88697028-88751945 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 88733053 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 446 (Y446H)

Ref Sequence

ENSEMBL: ENSMUSP00000147904 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000043526] [ENSMUST00000098519] [ENSMUST00000109626] [ENSMUST00000209206] [ENSMUST00000209532] [ENSMUST00000209559] [ENSMUST00000211554]

AlphaFold

Q80TQ2

Predicted Effect

possibly damaging
Transcript: ENSMUST00000043526
AA Change: Y631H

PolyPhen 2 Score 0.516 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000039834
Gene: ENSMUSG00000036712
AA Change: Y631H

Domain	Start	End	E-Value	Type
low complexity region	109	120	N/A	INTRINSIC
CAP_GLY	127	203	3.2e-18	SMART
CAP_GLY	232	303	5.37e-11	SMART
low complexity region	397	411	N/A	INTRINSIC
CAP_GLY	471	539	2.68e-20	SMART
Pfam:UCH	591	891	1.7e-12	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000098519
AA Change: Y631H

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000096119
Gene: ENSMUSG00000036712
AA Change: Y631H

Domain	Start	End	E-Value	Type
low complexity region	109	120	N/A	INTRINSIC
CAP_GLY	127	203	3.2e-18	SMART
CAP_GLY	232	303	5.37e-11	SMART
Pfam:CYLD_phos_site	307	470	6.5e-88	PFAM
CAP_GLY	471	539	2.68e-20	SMART
Pfam:UCH	590	893	2.1e-14	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000109626
AA Change: Y628H

PolyPhen 2 Score 0.873 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000105254
Gene: ENSMUSG00000036712
AA Change: Y628H

Domain	Start	End	E-Value	Type
low complexity region	109	120	N/A	INTRINSIC
CAP_GLY	127	203	3.2e-18	SMART
CAP_GLY	232	303	5.37e-11	SMART
Pfam:CYLD_phos_site	304	467	2.5e-88	PFAM
CAP_GLY	468	536	2.68e-20	SMART
Pfam:UCH	587	890	2e-14	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000209206
AA Change: Y446H

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

Predicted Effect

probably damaging
Transcript: ENSMUST00000209532
AA Change: Y631H

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

Predicted Effect

possibly damaging
Transcript: ENSMUST00000209559
AA Change: Y628H

PolyPhen 2 Score 0.873 (Sensitivity: 0.83; Specificity: 0.93)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000209722

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000210302

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000211038

Predicted Effect

possibly damaging
Transcript: ENSMUST00000211554
AA Change: Y628H

PolyPhen 2 Score 0.873 (Sensitivity: 0.83; Specificity: 0.93)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000211671

Coding Region Coverage

1x: 99.9%
3x: 99.5%
10x: 97.4%
20x: 91.9%

Validation Efficiency

MGI Phenotype

FUNCTION: This gene encodes a protein that is a member of the ubiquitin C-terminal hydrolase subfamily of the deubiquitinating enzyme family. Members of this family catalyze the removal of ubiquitin from a substrate or another ubiquitin molecule and thereby play important roles in regulating signaling pathways, recycling ubiquitin and regulating protein stability. This protein removes ubiquitin from K-63-linked ubiquitin chains from proteins involved in NF-kappaB signaling and thus acts as a negative regulator of this pathway. In humans mutations in this gene have been associated with cylindromatosis, an autosomal dominant predisposition to tumors of skin appendages. In mouse deficiency of this gene impairs thymocyte development and increases susceptibility to skin and colon tumors. A pseudogene of this gene has been identified on chromosome 1. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jan 2013]
PHENOTYPE: Various knockout models with different exon deletions have been created. Observed phenotypes include altered T cell and B cell development, susceptibility to induced skin tumors, resistance to lethal lung infection, high colon tumor incidence, kinky tails, and neonatal death due to lung dysfunction. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 73 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aars2	T	A	17: 45,508,623	L188*	probably null	Het
Acod1	C	T	14: 103,055,035	R332C	probably damaging	Het
Adamts3	T	A	5: 89,691,335	K852M	probably damaging	Het
Adm	A	T	7: 110,627,696		probably benign	Het
Aff4	A	G	11: 53,373,010	S286G	probably damaging	Het
Ank2	A	G	3: 126,959,651		probably null	Het
Aqr	A	T	2: 114,143,049	Y427*	probably null	Het
Arid1b	C	A	17: 4,994,956		probably benign	Het
Arpp21	T	A	9: 112,143,485	R259*	probably null	Het
Cep290	C	T	10: 100,543,321	A55V	possibly damaging	Het
Chsy3	GT	G	18: 59,176,166	163	probably null	Het
Clcn2	T	C	16: 20,713,654	E68G	possibly damaging	Het
Corin	T	A	5: 72,316,389	H699L	probably benign	Het
Dcst1	T	A	3: 89,352,576	E613V	probably damaging	Het
Dlk1	T	C	12: 109,455,581	C74R	probably damaging	Het
Dnah12	A	C	14: 26,697,341	K128T	probably benign	Het
Dspp	T	A	5: 104,178,451	S893R	unknown	Het
Dtl	A	T	1: 191,568,572		probably null	Het
F2rl1	T	A	13: 95,514,270	S35C	probably benign	Het
Fcgbp	A	T	7: 28,120,534	Y2562F	probably benign	Het
Fgf10	A	T	13: 118,715,508	D42V	probably benign	Het
Gm10271	A	T	10: 116,972,592	F6L	probably damaging	Het
Gm21190	T	A	5: 15,524,851	E256D	probably damaging	Het
Gm5157	A	G	7: 21,185,421	S66P	probably damaging	Het
Gm884	A	T	11: 103,613,792	M2450K	possibly damaging	Het
Hal	T	G	10: 93,490,916	L138R	probably damaging	Het
Hsd17b3	T	C	13: 64,059,470		probably null	Het
Lrsam1	T	C	2: 32,955,222	T94A	probably benign	Het
Macc1	T	C	12: 119,447,585	V696A	probably damaging	Het
Magi2	G	A	5: 19,227,291	M1I	probably null	Het
March7	C	A	2: 60,245,220	N674K	probably benign	Het
Mfap1b	A	G	2: 121,470,295	V34A	probably benign	Het
Mob3b	G	A	4: 35,084,069	S40L	probably benign	Het
Ndufs2	A	T	1: 171,236,418	V386E	probably damaging	Het
Nfic	C	T	10: 81,420,747	A19T	probably damaging	Het
Nfs1	G	A	2: 156,134,453	R174W	probably damaging	Het
Nin	G	T	12: 70,045,524	S670R	possibly damaging	Het
Nrxn1	T	C	17: 90,623,507	I754V	probably benign	Het
Nwd1	T	C	8: 72,653,573		probably null	Het
Olfr1231	T	A	2: 89,303,359	T78S	possibly damaging	Het
Olfr1238	T	A	2: 89,406,879	M67L	probably benign	Het
Olfr575	G	T	7: 102,955,009	N197K	probably benign	Het
Pcdhgb8	A	G	18: 37,763,449	E524G	probably damaging	Het
Phlpp1	A	T	1: 106,318,993	R638*	probably null	Het
Pkmyt1	G	C	17: 23,735,326	W360S	probably benign	Het
Plxnd1	C	A	6: 115,967,787		probably null	Het
Poldip3	A	T	15: 83,129,229	N322K	probably damaging	Het
Prmt3	A	T	7: 49,828,947	I419L	probably benign	Het
Prss36	A	T	7: 127,944,830	V123E	probably damaging	Het
Prss58	A	G	6: 40,897,769	I46T	probably damaging	Het
Rac1	T	C	5: 143,506,998		probably benign	Het
Rb1cc1	A	G	1: 6,233,996	Y36C	probably damaging	Het
Rif1	C	G	2: 52,095,844	L614V	probably damaging	Het
Rnd2	C	T	11: 101,468,999	L57F	probably damaging	Het
Rp1	A	T	1: 4,148,703	F951L	unknown	Het
Rps6ka5	G	T	12: 100,575,250	P417T	possibly damaging	Het
Ryr1	A	G	7: 29,067,637	W2967R	probably damaging	Het
Sacs	T	A	14: 61,205,543	S1679R	probably damaging	Het
Scn1a	A	C	2: 66,335,456	W153G	probably damaging	Het
Serpinb7	A	G	1: 107,445,996	Y114C	probably damaging	Het
Son	T	C	16: 91,658,904	M1513T	probably benign	Het
Spag8	C	T	4: 43,651,534	V447M	probably benign	Het
St3gal2	T	A	8: 110,969,553	Y257N	probably damaging	Het
Tars	A	T	15: 11,397,196	D40E	probably damaging	Het
Tlr3	T	C	8: 45,397,814	H158R	probably benign	Het
Tppp2	G	T	14: 51,918,935	V50L	probably benign	Het
Trrap	T	C	5: 144,810,184	S1503P	probably benign	Het
Ttll4	T	G	1: 74,685,391	S573R	probably damaging	Het
Vmn2r104	A	T	17: 20,029,485	N841K	probably damaging	Het
Vmn2r3	A	T	3: 64,259,647	C688S	probably damaging	Het
Vps16	T	C	2: 130,424,449		probably null	Het
Zfp608	G	A	18: 54,899,248	T540I	probably benign	Het
Zfp775	G	A	6: 48,619,816	R208Q	probably damaging	Het

Other mutations in Cyld

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00089:Cyld	APN	8	88705457	missense	probably benign	0.41
IGL00481:Cyld	APN	8	88707290	missense	probably damaging	1.00
IGL01013:Cyld	APN	8	88742362	missense	probably damaging	1.00
IGL01653:Cyld	APN	8	88741370	missense	probably damaging	1.00
IGL01700:Cyld	APN	8	88707099	missense	probably damaging	0.99
IGL01845:Cyld	APN	8	88705775	nonsense	probably null
IGL02366:Cyld	APN	8	88729753	missense	probably damaging	1.00
IGL02379:Cyld	APN	8	88744928	nonsense	probably null
IGL02506:Cyld	APN	8	88729590	missense	possibly damaging	0.86
IGL02563:Cyld	APN	8	88735894	missense	probably damaging	1.00
IGL02565:Cyld	APN	8	88741291	missense	probably damaging	1.00
IGL02814:Cyld	APN	8	88744897	missense	probably benign	0.29
PIT4131001:Cyld	UTSW	8	88746915	missense	probably damaging	0.98
R0101:Cyld	UTSW	8	88718300	critical splice donor site	probably null
R0122:Cyld	UTSW	8	88742292	missense	probably damaging	1.00
R0529:Cyld	UTSW	8	88729759	missense	probably benign	0.34
R0838:Cyld	UTSW	8	88741350	missense	probably benign	0.15
R1589:Cyld	UTSW	8	88709990	missense	possibly damaging	0.84
R1732:Cyld	UTSW	8	88731667	splice site	probably benign
R2029:Cyld	UTSW	8	88745312	missense	probably benign	0.09
R3701:Cyld	UTSW	8	88729551	missense	probably benign
R3798:Cyld	UTSW	8	88734930	missense	probably damaging	1.00
R4243:Cyld	UTSW	8	88730755	nonsense	probably null
R4244:Cyld	UTSW	8	88730755	nonsense	probably null
R4260:Cyld	UTSW	8	88741391	missense	probably damaging	1.00
R4458:Cyld	UTSW	8	88719301	missense	probably benign	0.24
R4551:Cyld	UTSW	8	88707134	missense	possibly damaging	0.95
R4718:Cyld	UTSW	8	88742305	missense	probably damaging	0.99
R4735:Cyld	UTSW	8	88729650	missense	probably damaging	1.00
R4753:Cyld	UTSW	8	88744816	splice site	probably null
R4966:Cyld	UTSW	8	88742301	missense	possibly damaging	0.55
R4975:Cyld	UTSW	8	88707232	missense	probably benign
R5375:Cyld	UTSW	8	88733036	missense	possibly damaging	0.77
R5647:Cyld	UTSW	8	88734926	missense	probably benign	0.10
R5741:Cyld	UTSW	8	88744846	missense	probably damaging	1.00
R5837:Cyld	UTSW	8	88741404	missense	probably damaging	0.99
R5931:Cyld	UTSW	8	88729842	splice site	probably null
R5970:Cyld	UTSW	8	88732993	missense	probably damaging	0.99
R6165:Cyld	UTSW	8	88746933	missense	possibly damaging	0.88
R7135:Cyld	UTSW	8	88744892	missense	possibly damaging	0.93
R7667:Cyld	UTSW	8	88742302	missense	probably benign	0.01
R7858:Cyld	UTSW	8	88709988	missense	probably damaging	0.98
R7912:Cyld	UTSW	8	88734897	missense	probably damaging	1.00
R8076:Cyld	UTSW	8	88729718	missense	probably benign	0.00
R8276:Cyld	UTSW	8	88734928	missense	probably benign	0.06
R8282:Cyld	UTSW	8	88705415	missense	probably benign	0.06
R8348:Cyld	UTSW	8	88729569	missense	probably damaging	1.00
R8448:Cyld	UTSW	8	88729569	missense	probably damaging	1.00
R8540:Cyld	UTSW	8	88746940	missense	probably damaging	1.00
R8676:Cyld	UTSW	8	88729510	missense	probably benign	0.02
R8710:Cyld	UTSW	8	88709895	missense	probably damaging	1.00
R8957:Cyld	UTSW	8	88705782	missense	probably damaging	0.97
R9329:Cyld	UTSW	8	88730720	missense	probably benign	0.22
RF016:Cyld	UTSW	8	88705441	nonsense	probably null
X0010:Cyld	UTSW	8	88746912	missense	probably damaging	0.99

Predicted Primers

PCR Primer
(F):5'- CTGCTGTCTTGACACATGAATTC -3'
(R):5'- CACCTCATCTGCTTTTAGTACAGTG -3'

Sequencing Primer
(F):5'- GACACATGAATTCTTATGCATTGCTC -3'
(R):5'- CACTGAAATAAACAGAAGCAGAAGAC -3'

Posted On

2017-06-26