Incidental Mutation 'R2029:Cyld'
ID 220973
Institutional Source Beutler Lab
Gene Symbol Cyld
Ensembl Gene ENSMUSG00000036712
Gene Name CYLD lysine 63 deubiquitinase
Synonyms CYLD1, C130039D01Rik, 2900009M21Rik, 2010013M14Rik
MMRRC Submission 040036-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R2029 (G1)
Quality Score 225
Status Validated
Chromosome 8
Chromosomal Location 89423656-89478573 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 89471940 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Lysine to Arginine at position 857 (K857R)
Ref Sequence ENSEMBL: ENSMUSP00000039834 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000043526] [ENSMUST00000098519] [ENSMUST00000109626] [ENSMUST00000209206] [ENSMUST00000209532] [ENSMUST00000209559] [ENSMUST00000211554]
AlphaFold Q80TQ2
Predicted Effect probably benign
Transcript: ENSMUST00000043526
AA Change: K857R

PolyPhen 2 Score 0.090 (Sensitivity: 0.93; Specificity: 0.85)
SMART Domains Protein: ENSMUSP00000039834
Gene: ENSMUSG00000036712
AA Change: K857R

DomainStartEndE-ValueType
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 benign
Transcript: ENSMUST00000098519
AA Change: K857R

PolyPhen 2 Score 0.059 (Sensitivity: 0.94; Specificity: 0.84)
SMART Domains Protein: ENSMUSP00000096119
Gene: ENSMUSG00000036712
AA Change: K857R

DomainStartEndE-ValueType
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 benign
Transcript: ENSMUST00000109626
AA Change: K854R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000105254
Gene: ENSMUSG00000036712
AA Change: K854R

DomainStartEndE-ValueType
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
AA Change: K672R

PolyPhen 2 Score 0.018 (Sensitivity: 0.95; Specificity: 0.80)
Predicted Effect probably benign
Transcript: ENSMUST00000209532
AA Change: K857R

PolyPhen 2 Score 0.059 (Sensitivity: 0.94; Specificity: 0.84)
Predicted Effect probably benign
Transcript: ENSMUST00000209559
AA Change: K854R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
Predicted Effect probably benign
Transcript: ENSMUST00000211554
AA Change: K854R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000209722
Meta Mutation Damage Score 0.0898 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.5%
  • 10x: 96.8%
  • 20x: 93.8%
Validation Efficiency 98% (97/99)
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: 100 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adam18 C G 8: 25,140,893 (GRCm39) G286A probably damaging Het
Adcy1 G A 11: 7,089,142 (GRCm39) A519T probably benign Het
Anxa2 T A 9: 69,371,762 (GRCm39) S2T possibly damaging Het
Ap3m1 G A 14: 21,089,217 (GRCm39) S261L possibly damaging Het
Baz2b A T 2: 59,743,067 (GRCm39) probably benign Het
Brdt T A 5: 107,507,090 (GRCm39) S497T probably benign Het
Cdh11 A G 8: 103,406,404 (GRCm39) F23S probably benign Het
Cdh16 A C 8: 105,344,434 (GRCm39) L540R probably damaging Het
Ces5a A T 8: 94,261,205 (GRCm39) L74Q probably damaging Het
Cfap69 A G 5: 5,654,306 (GRCm39) S543P probably damaging Het
Cfap74 T C 4: 155,526,538 (GRCm39) I763T possibly damaging Het
Cma1 T A 14: 56,181,191 (GRCm39) R58S possibly damaging Het
Csmd3 C T 15: 47,701,975 (GRCm39) D1599N probably damaging Het
Cyp3a16 T C 5: 145,388,667 (GRCm39) D270G probably damaging Het
D1Pas1 T C 1: 186,700,286 (GRCm39) S72P possibly damaging Het
Ddx3y T C Y: 1,266,389 (GRCm39) E331G probably benign Het
Degs1l T A 1: 180,882,496 (GRCm39) I86K probably benign Het
Dis3l2 T C 1: 86,782,189 (GRCm39) probably benign Het
Dop1a G T 9: 86,403,418 (GRCm39) W1539C probably damaging Het
Dop1b A G 16: 93,566,323 (GRCm39) K917E probably benign Het
Ecpas G A 4: 58,844,165 (GRCm39) R534* probably null Het
Efcab3 T C 11: 104,990,851 (GRCm39) I5462T probably damaging Het
Eif1ad15 A T 12: 88,288,191 (GRCm39) S21T unknown Het
Epo A G 5: 137,483,447 (GRCm39) probably benign Het
Figla T A 6: 85,997,624 (GRCm39) probably benign Het
Flvcr1 T C 1: 190,753,353 (GRCm39) D273G probably benign Het
Fryl T A 5: 73,179,465 (GRCm39) R304* probably null Het
Gcm1 T G 9: 77,972,326 (GRCm39) D422E possibly damaging Het
Get3 A T 8: 85,746,403 (GRCm39) Y148* probably null Het
Ggt6 A G 11: 72,328,367 (GRCm39) D251G possibly damaging Het
Git2 A G 5: 114,904,511 (GRCm39) probably null Het
Gm18856 A T 13: 14,139,376 (GRCm39) probably benign Het
Gm20939 T A 17: 95,183,252 (GRCm39) probably benign Het
Gpr176 A G 2: 118,109,913 (GRCm39) Y449H probably benign Het
H2-Eb1 A G 17: 34,533,366 (GRCm39) E196G probably damaging Het
H2-M10.6 A G 17: 37,124,799 (GRCm39) T239A possibly damaging Het
Haus5 T C 7: 30,358,825 (GRCm39) N237S possibly damaging Het
Hectd3 T C 4: 116,857,882 (GRCm39) M605T probably damaging Het
Hps3 T C 3: 20,084,691 (GRCm39) I166V probably benign Het
Ighv5-21 A T 12: 114,286,434 (GRCm39) probably benign Het
Kdm6b C T 11: 69,294,418 (GRCm39) G1218D unknown Het
Klhl30 A G 1: 91,285,636 (GRCm39) probably null Het
Kmt2a A T 9: 44,729,747 (GRCm39) S3523R probably benign Het
Lnpep A T 17: 17,788,661 (GRCm39) N481K probably damaging Het
Lrp1b T C 2: 41,231,861 (GRCm39) H1203R probably benign Het
Lrrc8a C T 2: 30,146,661 (GRCm39) R492W probably damaging Het
Magel2 T A 7: 62,030,342 (GRCm39) V1082D unknown Het
Memo1 A C 17: 74,552,049 (GRCm39) H82Q probably null Het
Myh13 A T 11: 67,252,115 (GRCm39) T1408S probably benign Het
Myh2 A T 11: 67,085,451 (GRCm39) N1792Y possibly damaging Het
Myo1e A T 9: 70,275,969 (GRCm39) N728I possibly damaging Het
Myo1e T C 9: 70,285,997 (GRCm39) probably benign Het
Myo5c T C 9: 75,196,337 (GRCm39) probably benign Het
Or11l3 T A 11: 58,516,319 (GRCm39) L184F probably damaging Het
Or1e19 A G 11: 73,316,188 (GRCm39) V207A probably benign Het
Or2d2b T C 7: 106,705,643 (GRCm39) I142V probably benign Het
Or4c11c T A 2: 88,661,749 (GRCm39) M96K possibly damaging Het
Or51g1 T A 7: 102,633,478 (GRCm39) T298S probably damaging Het
Or52e3 T C 7: 102,868,967 (GRCm39) F14S probably damaging Het
Parp2 C T 14: 51,047,543 (GRCm39) A18V probably benign Het
Peli1 T A 11: 21,098,110 (GRCm39) C282S probably damaging Het
Phf8-ps G T 17: 33,286,598 (GRCm39) S68* probably null Het
Piezo2 T C 18: 63,252,006 (GRCm39) M404V possibly damaging Het
Pkn1 T A 8: 84,404,592 (GRCm39) Q496L possibly damaging Het
Pla2r1 A T 2: 60,262,317 (GRCm39) F1093L probably damaging Het
Ppp2r3d A G 9: 101,022,680 (GRCm39) V323A probably damaging Het
Pramel16 T A 4: 143,676,453 (GRCm39) Y217F probably benign Het
Prg2 C T 2: 84,812,342 (GRCm39) probably benign Het
Ptprb G A 10: 116,182,958 (GRCm39) G1545S probably benign Het
Rbm19 A G 5: 120,258,307 (GRCm39) D174G possibly damaging Het
Rhbdf2 T A 11: 116,491,974 (GRCm39) T526S probably damaging Het
Rpusd4 A G 9: 35,179,310 (GRCm39) N42S probably benign Het
Ryr3 T A 2: 112,477,361 (GRCm39) Q4455L possibly damaging Het
Sema4a G T 3: 88,358,668 (GRCm39) H30Q probably damaging Het
Skint1 G A 4: 111,878,653 (GRCm39) probably null Het
Slc1a3 A G 15: 8,675,153 (GRCm39) V284A probably benign Het
Slc30a9 A T 5: 67,497,318 (GRCm39) K288* probably null Het
Slc36a1 G T 11: 55,119,164 (GRCm39) A380S probably benign Het
Slc47a1 G A 11: 61,268,833 (GRCm39) probably benign Het
Snx19 A T 9: 30,340,296 (GRCm39) E478V probably benign Het
Spag6 T C 2: 18,738,916 (GRCm39) probably benign Het
Stag1 A T 9: 100,668,740 (GRCm39) T223S probably damaging Het
Terb1 A T 8: 105,224,732 (GRCm39) probably benign Het
Terf1 A G 1: 15,876,170 (GRCm39) D90G possibly damaging Het
Tex15 A G 8: 34,061,302 (GRCm39) D518G probably damaging Het
Tmem174 T A 13: 98,773,546 (GRCm39) M95L possibly damaging Het
Tnnt3 GTCCAGGCATCTC GTC 7: 142,066,364 (GRCm39) probably benign Het
Usp28 A G 9: 48,896,803 (GRCm39) D8G probably benign Het
Vmn2r105 T C 17: 20,444,840 (GRCm39) T551A probably damaging Het
Vmn2r107 A G 17: 20,595,549 (GRCm39) I701V probably benign Het
Vmn2r13 A C 5: 109,339,943 (GRCm39) F11V probably benign Het
Vmn2r85 G C 10: 130,261,443 (GRCm39) S298* probably null Het
Wdr6 C G 9: 108,452,554 (GRCm39) W443S probably damaging Het
Wipi1 A G 11: 109,474,016 (GRCm39) V210A probably damaging Het
Zfp317 A G 9: 19,556,532 (GRCm39) T47A probably benign Het
Zfp61 T C 7: 23,991,714 (GRCm39) T146A probably benign Het
Zfp964 A G 8: 70,116,567 (GRCm39) E389G unknown Het
Zfyve16 T C 13: 92,640,985 (GRCm39) D1253G probably damaging Het
Zpld2 T C 4: 133,929,669 (GRCm39) K212R possibly damaging Het
Zswim7 G A 11: 62,158,299 (GRCm39) probably benign Het
Other mutations in Cyld
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
R4735:Cyld UTSW 8 89,456,278 (GRCm39) missense probably damaging 1.00
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'- AGAGTCTGCTCCCTTGCAAC -3'
(R):5'- ACATTGTTCCTTAGTCTGGGTAGC -3'

Sequencing Primer
(F):5'- CCTTGCAACATGGTATTAGCTCATG -3'
(R):5'- TTCACACACATGTTCTCACTAGGAAG -3'
Posted On 2014-08-25