Mutagenetix > Incidental Mutation

Incidental Mutation 'R4735:Cyld'

356478

Institutional Source

Beutler Lab

Gene Symbol

Cyld

Ensembl Gene

ENSMUSG00000036712

Gene Name

CYLD lysine 63 deubiquitinase

Synonyms

CYLD1, C130039D01Rik, 2900009M21Rik, 2010013M14Rik

MMRRC Submission

041962-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R4735 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

89423656-89478573 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 89456278 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 443 (S443P)

Ref Sequence

ENSEMBL: ENSMUSP00000147654 (fasta)

Gene Model

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

AlphaFold

Q80TQ2

Predicted Effect

probably damaging
Transcript: ENSMUST00000043526
AA Change: S443P

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000039834
Gene: ENSMUSG00000036712
AA Change: S443P

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: S443P

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000096119
Gene: ENSMUSG00000036712
AA Change: S443P

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

probably damaging
Transcript: ENSMUST00000109626
AA Change: S440P

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000105254
Gene: ENSMUSG00000036712
AA Change: S440P

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 benign
Transcript: ENSMUST00000209206

Predicted Effect

probably damaging
Transcript: ENSMUST00000209532
AA Change: S443P

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)

Predicted Effect

probably damaging
Transcript: ENSMUST00000209559
AA Change: S440P

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000209722

Predicted Effect

probably damaging
Transcript: ENSMUST00000211554
AA Change: S440P

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000210302

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000211038

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.1%
20x: 95.0%

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: 133 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2700049A03Rik	T	A	12: 71,262,897 (GRCm39)	I1410N	possibly damaging	Het
9230106D20Rik	T	C	10: 19,536,001 (GRCm39)		noncoding transcript	Het
Acsf3	T	A	8: 123,508,218 (GRCm39)	I238N	probably damaging	Het
Ahctf1	T	C	1: 179,580,964 (GRCm39)	N1746S	probably benign	Het
Akap3	T	C	6: 126,842,601 (GRCm39)	S407P	probably damaging	Het
Ankfy1	T	A	11: 72,621,437 (GRCm39)	M241K	probably benign	Het
Ano7	C	A	1: 93,328,216 (GRCm39)	T622K	probably benign	Het
App	T	C	16: 84,900,202 (GRCm39)	T83A	probably damaging	Het
Arhgef28	T	A	13: 98,036,237 (GRCm39)	E1674V	probably damaging	Het
Asb2	C	A	12: 103,291,317 (GRCm39)	V489L	probably benign	Het
Atrn	T	C	2: 130,862,910 (GRCm39)	V1330A	probably benign	Het
Bltp1	T	A	3: 37,059,116 (GRCm39)	N3267K	possibly damaging	Het
Brca1	A	G	11: 101,383,001 (GRCm39)		probably null	Het
Bspry	G	A	4: 62,404,762 (GRCm39)	R186Q	probably damaging	Het
Ccdc168	A	G	1: 44,100,861 (GRCm39)	I79T	probably benign	Het
Cdkn2d	C	G	9: 21,202,185 (GRCm39)	V21L	probably benign	Het
Celsr1	T	A	15: 85,790,230 (GRCm39)		probably null	Het
Ckap4	A	G	10: 84,369,384 (GRCm39)	V116A	possibly damaging	Het
Crb3	A	G	17: 57,372,207 (GRCm39)	T85A	probably damaging	Het
Cyp27a1	T	G	1: 74,776,366 (GRCm39)	V434G	possibly damaging	Het
Cyp2b13	A	G	7: 25,787,720 (GRCm39)	T339A	probably benign	Het
Dars1	A	T	1: 128,303,971 (GRCm39)	L252*	probably null	Het
Dcaf10	G	A	4: 45,372,769 (GRCm39)	R394Q	possibly damaging	Het
Ddx55	T	C	5: 124,704,539 (GRCm39)	F382S	probably damaging	Het
Dmtf1l	T	A	X: 125,722,217 (GRCm39)	K296M	probably damaging	Het
Dnah7b	G	A	1: 46,106,115 (GRCm39)	R33Q	unknown	Het
Dnm2	G	T	9: 21,385,883 (GRCm39)	S302I	probably damaging	Het
Dock4	T	A	12: 40,681,525 (GRCm39)	F75I	probably benign	Het
Dpp10	T	C	1: 123,326,356 (GRCm39)	N365S	probably benign	Het
Dpy19l3	G	T	7: 35,422,146 (GRCm39)	Q236K	probably benign	Het
Dsp	T	C	13: 38,380,016 (GRCm39)	S1655P	probably damaging	Het
Ebpl	A	T	14: 61,579,567 (GRCm39)	I117N	probably damaging	Het
Edc4	T	A	8: 106,613,818 (GRCm39)	V386E	probably damaging	Het
Eif2s2	T	A	2: 154,720,467 (GRCm39)		probably null	Het
Elob	A	T	17: 24,046,562 (GRCm39)		probably null	Het
Enox2	T	C	X: 48,158,554 (GRCm39)	I71V	probably damaging	Het
Fez1	A	T	9: 36,772,141 (GRCm39)	K149*	probably null	Het
Fhip2a	A	G	19: 57,359,661 (GRCm39)	E67G	probably damaging	Het
Fign	A	G	2: 63,810,782 (GRCm39)	Y163H	probably damaging	Het
Flnc	G	A	6: 29,455,812 (GRCm39)	G2048S	probably damaging	Het
Fras1	A	G	5: 96,736,022 (GRCm39)	D539G	probably benign	Het
Frmd4b	T	C	6: 97,436,220 (GRCm39)		probably benign	Het
Gan	C	T	8: 117,920,970 (GRCm39)	T402M	probably damaging	Het
Ganc	T	A	2: 120,267,104 (GRCm39)		silent	Het
Ggt6	C	A	11: 72,327,425 (GRCm39)	R103S	probably benign	Het
Gli2	T	C	1: 118,768,052 (GRCm39)	D725G	probably damaging	Het
Gm15446	T	A	5: 110,090,818 (GRCm39)	C357S	probably damaging	Het
Gm44501	A	G	17: 40,889,810 (GRCm39)	N108S	probably benign	Het
Gm6309	A	T	5: 146,105,054 (GRCm39)	D286E	probably damaging	Het
Gm6358	G	A	16: 88,937,848 (GRCm39)	G29E	unknown	Het
Grik5	A	G	7: 24,757,713 (GRCm39)	I422T	probably damaging	Het
Grin2c	A	G	11: 115,140,422 (GRCm39)	I1232T	possibly damaging	Het
Gsg1	C	T	6: 135,214,405 (GRCm39)	R365H	possibly damaging	Het
H2-M2	A	G	17: 37,794,135 (GRCm39)	S30P	possibly damaging	Het
Hcfc2	A	G	10: 82,547,914 (GRCm39)	D302G	probably damaging	Het
Hk2	T	C	6: 82,721,955 (GRCm39)	D128G	probably benign	Het
Hmcn2	C	A	2: 31,273,787 (GRCm39)	Q1380K	probably benign	Het
Hsp90b1	G	T	10: 86,529,819 (GRCm39)	P617T	probably damaging	Het
Htr1d	A	G	4: 136,170,197 (GRCm39)	E142G	probably benign	Het
Hydin	G	A	8: 111,282,264 (GRCm39)		probably null	Het
Il1r1	T	A	1: 40,332,455 (GRCm39)	N81K	probably benign	Het
Inpp5b	T	C	4: 124,677,760 (GRCm39)	S407P	probably damaging	Het
Itpkb	T	C	1: 180,245,780 (GRCm39)	Y766H	probably damaging	Het
Lyrm2	T	A	4: 32,801,150 (GRCm39)	I65N	probably damaging	Het
Mink1	T	A	11: 70,500,086 (GRCm39)		probably null	Het
Mkrn3	C	T	7: 62,069,452 (GRCm39)	R113H	probably damaging	Het
Msx3	G	A	7: 139,627,798 (GRCm39)	A157V	probably damaging	Het
Nrxn2	T	G	19: 6,548,484 (GRCm39)	V59G	possibly damaging	Het
Nt5c3b	T	C	11: 100,331,732 (GRCm39)	T12A	probably benign	Het
Nwd2	G	A	5: 63,965,594 (GRCm39)	R1726Q	probably benign	Het
Nynrin	A	G	14: 56,107,625 (GRCm39)	T911A	probably benign	Het
Or11i1	T	A	3: 106,728,996 (GRCm39)	Y293F	probably damaging	Het
Or4p18	T	C	2: 88,233,267 (GRCm39)	T4A	probably benign	Het
Or51aa5	A	G	7: 103,167,030 (GRCm39)	I187T	possibly damaging	Het
Or51af1	C	T	7: 103,141,267 (GRCm39)	V273M	possibly damaging	Het
Or52n20	C	T	7: 104,320,200 (GRCm39)	T97I	probably benign	Het
Or5p66	A	G	7: 107,885,520 (GRCm39)	M271T	probably benign	Het
Or6c212	A	G	10: 129,558,792 (GRCm39)	I207T	probably benign	Het
Patl1	G	T	19: 11,899,869 (GRCm39)	M220I	probably benign	Het
Pcnx2	A	T	8: 126,554,780 (GRCm39)		probably null	Het
Pigr	A	T	1: 130,774,291 (GRCm39)	T424S	probably damaging	Het
Pik3c2b	T	A	1: 132,994,787 (GRCm39)	D250E	probably benign	Het
Ppa2	G	A	3: 133,076,186 (GRCm39)	E272K	probably benign	Het
Pramel7	G	A	2: 87,321,187 (GRCm39)	Q283*	probably null	Het
Prelid3b	A	G	2: 174,307,683 (GRCm39)	I81T	probably benign	Het
Prpf38a	T	C	4: 108,436,242 (GRCm39)	I24V	possibly damaging	Het
Ptger2	A	G	14: 45,239,295 (GRCm39)	D311G	possibly damaging	Het
Rab4b	A	T	7: 26,872,191 (GRCm39)		probably benign	Het
Rad17	A	C	13: 100,755,637 (GRCm39)	D581E	probably damaging	Het
Samd11	T	C	4: 156,333,230 (GRCm39)	T333A	probably benign	Het
Scaf4	C	T	16: 90,049,320 (GRCm39)	D256N	unknown	Het
Serinc2	A	G	4: 130,157,438 (GRCm39)	F82L	probably benign	Het
Serpina3g	T	A	12: 104,205,372 (GRCm39)	V37E	probably damaging	Het
Serpinb9c	T	A	13: 33,334,254 (GRCm39)	M263L	probably benign	Het
Shbg	A	G	11: 69,508,326 (GRCm39)	I67T	possibly damaging	Het
Slc25a48	G	A	13: 56,596,887 (GRCm39)		probably null	Het
Slc25a54	T	C	3: 109,005,923 (GRCm39)	W144R	probably damaging	Het
Slc34a1	A	T	13: 55,561,397 (GRCm39)	T621S	probably benign	Het
Slc6a18	A	T	13: 73,814,554 (GRCm39)	C419S	probably benign	Het
Smc5	A	T	19: 23,220,069 (GRCm39)	D389E	probably benign	Het
Smco3	T	A	6: 136,808,636 (GRCm39)	E79D	probably damaging	Het
Sox5	A	G	6: 143,906,561 (GRCm39)	F298S	probably damaging	Het
Sphkap	A	G	1: 83,256,838 (GRCm39)	S304P	probably benign	Het
Tcea2	C	T	2: 181,328,514 (GRCm39)	T211I	probably damaging	Het
Tcf4	G	T	18: 69,697,226 (GRCm39)	S34I	possibly damaging	Het
Tlr4	C	T	4: 66,759,435 (GRCm39)	R743C	probably damaging	Het
Tmem183a	T	C	1: 134,288,620 (GRCm39)	E67G	probably damaging	Het
Tpr	C	T	1: 150,317,947 (GRCm39)	R2152C	possibly damaging	Het
Trbv15	T	C	6: 41,118,358 (GRCm39)	I38T	probably benign	Het
Treh	G	A	9: 44,592,849 (GRCm39)	A125T	probably damaging	Het
Trio	A	T	15: 27,752,875 (GRCm39)		probably null	Het
Ttn	A	G	2: 76,782,293 (GRCm39)	V981A	probably damaging	Het
Uap1l1	A	G	2: 25,252,732 (GRCm39)	L436P	probably damaging	Het
Uba7	A	T	9: 107,854,115 (GRCm39)	I182F	possibly damaging	Het
Unc13c	A	T	9: 73,600,620 (GRCm39)	S1375T	probably benign	Het
Usp48	C	CT	4: 137,360,680 (GRCm39)		probably null	Het
Utp20	A	C	10: 88,652,780 (GRCm39)	V378G	possibly damaging	Het
Vmn1r69	A	T	7: 10,314,926 (GRCm39)		probably benign	Het
Vmn1r86	A	T	7: 12,836,221 (GRCm39)	H218Q	probably damaging	Het
Vmn2r121	T	A	X: 123,038,335 (GRCm39)	I562L	probably benign	Het
Vmn2r45	A	T	7: 8,486,472 (GRCm39)	I272N	probably damaging	Het
Wdr90	A	G	17: 26,078,424 (GRCm39)	V320A	probably benign	Het
Wfikkn1	A	G	17: 26,097,367 (GRCm39)	V319A	possibly damaging	Het
Whamm	A	G	7: 81,221,122 (GRCm39)	D18G	probably benign	Het
Wrn	T	A	8: 33,775,250 (GRCm39)	I605F	probably damaging	Het
Zdhhc18	A	G	4: 133,341,178 (GRCm39)	F232L	probably damaging	Het
Zfp41	T	C	15: 75,490,609 (GRCm39)	I187T	probably benign	Het
Zfp418	A	G	7: 7,185,561 (GRCm39)	Y508C	probably damaging	Het
Zfp560	T	G	9: 20,260,347 (GRCm39)	I172L	probably benign	Het
Zfp943	A	T	17: 22,211,391 (GRCm39)	D159V	probably benign	Het
Zfp955a	T	C	17: 33,460,696 (GRCm39)	I479V	probably benign	Het
Zfpm1	T	A	8: 123,062,219 (GRCm39)	V426D	probably benign	Het
Zic1	C	T	9: 91,246,558 (GRCm39)	M171I	possibly damaging	Het

Other mutations in Cyld

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00089:Cyld	APN	8	89,432,085 (GRCm39)	missense	probably benign	0.41
IGL00481:Cyld	APN	8	89,433,918 (GRCm39)	missense	probably damaging	1.00
IGL01013:Cyld	APN	8	89,468,990 (GRCm39)	missense	probably damaging	1.00
IGL01653:Cyld	APN	8	89,467,998 (GRCm39)	missense	probably damaging	1.00
IGL01700:Cyld	APN	8	89,433,727 (GRCm39)	missense	probably damaging	0.99
IGL01845:Cyld	APN	8	89,432,403 (GRCm39)	nonsense	probably null
IGL02366:Cyld	APN	8	89,456,381 (GRCm39)	missense	probably damaging	1.00
IGL02379:Cyld	APN	8	89,471,556 (GRCm39)	nonsense	probably null
IGL02506:Cyld	APN	8	89,456,218 (GRCm39)	missense	possibly damaging	0.86
IGL02563:Cyld	APN	8	89,462,522 (GRCm39)	missense	probably damaging	1.00
IGL02565:Cyld	APN	8	89,467,919 (GRCm39)	missense	probably damaging	1.00
IGL02814:Cyld	APN	8	89,471,525 (GRCm39)	missense	probably benign	0.29
PIT4131001:Cyld	UTSW	8	89,473,543 (GRCm39)	missense	probably damaging	0.98
R0101:Cyld	UTSW	8	89,444,928 (GRCm39)	critical splice donor site	probably null
R0122:Cyld	UTSW	8	89,468,920 (GRCm39)	missense	probably damaging	1.00
R0529:Cyld	UTSW	8	89,456,387 (GRCm39)	missense	probably benign	0.34
R0838:Cyld	UTSW	8	89,467,978 (GRCm39)	missense	probably benign	0.15
R1589:Cyld	UTSW	8	89,436,618 (GRCm39)	missense	possibly damaging	0.84
R1732:Cyld	UTSW	8	89,458,295 (GRCm39)	splice site	probably benign
R2029:Cyld	UTSW	8	89,471,940 (GRCm39)	missense	probably benign	0.09
R3701:Cyld	UTSW	8	89,456,179 (GRCm39)	missense	probably benign
R3798:Cyld	UTSW	8	89,461,558 (GRCm39)	missense	probably damaging	1.00
R4243:Cyld	UTSW	8	89,457,383 (GRCm39)	nonsense	probably null
R4244:Cyld	UTSW	8	89,457,383 (GRCm39)	nonsense	probably null
R4260:Cyld	UTSW	8	89,468,019 (GRCm39)	missense	probably damaging	1.00
R4458:Cyld	UTSW	8	89,445,929 (GRCm39)	missense	probably benign	0.24
R4551:Cyld	UTSW	8	89,433,762 (GRCm39)	missense	possibly damaging	0.95
R4718:Cyld	UTSW	8	89,468,933 (GRCm39)	missense	probably damaging	0.99
R4753:Cyld	UTSW	8	89,471,444 (GRCm39)	splice site	probably null
R4966:Cyld	UTSW	8	89,468,929 (GRCm39)	missense	possibly damaging	0.55
R4975:Cyld	UTSW	8	89,433,860 (GRCm39)	missense	probably benign
R5375:Cyld	UTSW	8	89,459,664 (GRCm39)	missense	possibly damaging	0.77
R5647:Cyld	UTSW	8	89,461,554 (GRCm39)	missense	probably benign	0.10
R5741:Cyld	UTSW	8	89,471,474 (GRCm39)	missense	probably damaging	1.00
R5837:Cyld	UTSW	8	89,468,032 (GRCm39)	missense	probably damaging	0.99
R5931:Cyld	UTSW	8	89,456,470 (GRCm39)	splice site	probably null
R5970:Cyld	UTSW	8	89,459,621 (GRCm39)	missense	probably damaging	0.99
R5992:Cyld	UTSW	8	89,459,681 (GRCm39)	missense	probably damaging	1.00
R6165:Cyld	UTSW	8	89,473,561 (GRCm39)	missense	possibly damaging	0.88
R7135:Cyld	UTSW	8	89,471,520 (GRCm39)	missense	possibly damaging	0.93
R7667:Cyld	UTSW	8	89,468,930 (GRCm39)	missense	probably benign	0.01
R7858:Cyld	UTSW	8	89,436,616 (GRCm39)	missense	probably damaging	0.98
R7912:Cyld	UTSW	8	89,461,525 (GRCm39)	missense	probably damaging	1.00
R8076:Cyld	UTSW	8	89,456,346 (GRCm39)	missense	probably benign	0.00
R8276:Cyld	UTSW	8	89,461,556 (GRCm39)	missense	probably benign	0.06
R8282:Cyld	UTSW	8	89,432,043 (GRCm39)	missense	probably benign	0.06
R8348:Cyld	UTSW	8	89,456,197 (GRCm39)	missense	probably damaging	1.00
R8448:Cyld	UTSW	8	89,456,197 (GRCm39)	missense	probably damaging	1.00
R8540:Cyld	UTSW	8	89,473,568 (GRCm39)	missense	probably damaging	1.00
R8676:Cyld	UTSW	8	89,456,138 (GRCm39)	missense	probably benign	0.02
R8710:Cyld	UTSW	8	89,436,523 (GRCm39)	missense	probably damaging	1.00
R8957:Cyld	UTSW	8	89,432,410 (GRCm39)	missense	probably damaging	0.97
R9329:Cyld	UTSW	8	89,457,348 (GRCm39)	missense	probably benign	0.22
RF016:Cyld	UTSW	8	89,432,069 (GRCm39)	nonsense	probably null
X0010:Cyld	UTSW	8	89,473,540 (GRCm39)	missense	probably damaging	0.99

Predicted Primers

PCR Primer
(F):5'- TTTTCATAGTTGCAGAAGACCCTG -3'
(R):5'- GGCCAAATTAAATTACCAGTTCCAG -3'

Sequencing Primer
(F):5'- CTGCAAAGTCACTTACAGAGATGTC -3'
(R):5'- ATTACCAGTTCCAGTCCAGCTAG -3'

Posted On

2015-11-11