Incidental Mutation 'PIT4131001:Cyld'
ID 523218
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 # PIT4131001 (G1)
Quality Score 225.009
Status Validated
Chromosome 8
Chromosomal Location 89423656-89478573 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 89473543 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Proline at position 739 (S739P)
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: S924P

PolyPhen 2 Score 0.546 (Sensitivity: 0.88; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000039834
Gene: ENSMUSG00000036712
AA Change: S924P

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: S924P

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000096119
Gene: ENSMUSG00000036712
AA Change: S924P

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 possibly damaging
Transcript: ENSMUST00000109626
AA Change: S921P

PolyPhen 2 Score 0.770 (Sensitivity: 0.85; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000105254
Gene: ENSMUSG00000036712
AA Change: S921P

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 damaging
Transcript: ENSMUST00000209206
AA Change: S739P

PolyPhen 2 Score 0.975 (Sensitivity: 0.76; Specificity: 0.96)
Predicted Effect probably benign
Transcript: ENSMUST00000209532
AA Change: S924P

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
Predicted Effect possibly damaging
Transcript: ENSMUST00000209559
AA Change: S921P

PolyPhen 2 Score 0.770 (Sensitivity: 0.85; Specificity: 0.92)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000209722
Predicted Effect possibly damaging
Transcript: ENSMUST00000211554
AA Change: S921P

PolyPhen 2 Score 0.770 (Sensitivity: 0.85; Specificity: 0.92)
Coding Region Coverage
  • 1x: 0.0%
  • 3x: 0.0%
  • 10x: 0.0%
  • 20x: 0.0%
Validation Efficiency 92% (126/137)
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: 129 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700010B08Rik C T 2: 173,561,599 (GRCm39) probably benign Het
Alpk2 G A 18: 65,439,450 (GRCm39) H648Y possibly damaging Het
Ambp A G 4: 63,062,502 (GRCm39) Y246H probably damaging Het
Amz1 T C 5: 140,735,088 (GRCm39) probably null Het
Anks6 G A 4: 47,027,109 (GRCm39) T703I probably damaging Het
Armc2 A G 10: 41,823,883 (GRCm39) probably benign Het
Atp7b T A 8: 22,484,672 (GRCm39) I1347F probably damaging Het
Atp8a1 C T 5: 67,779,945 (GRCm39) W1149* probably null Het
Auh A G 13: 52,995,046 (GRCm39) I173T probably damaging Het
Axin2 T C 11: 108,814,829 (GRCm39) L239P possibly damaging Het
Bbs1 A T 19: 4,949,287 (GRCm39) F257L possibly damaging Het
Cacna2d2 C T 9: 107,401,867 (GRCm39) P774L probably damaging Het
Card6 A G 15: 5,137,788 (GRCm39) L22P probably damaging Het
Ccdc171 C T 4: 83,579,946 (GRCm39) Het
Ccn2 T C 10: 24,471,988 (GRCm39) V70A probably damaging Het
Cdc14a T A 3: 116,122,310 (GRCm39) N219I possibly damaging Het
Cfap65 G T 1: 74,967,501 (GRCm39) N192K probably benign Het
Col14a1 T C 15: 55,312,272 (GRCm39) probably benign Het
Col5a1 A G 2: 27,914,665 (GRCm39) T94A probably benign Het
Col6a5 T C 9: 105,759,113 (GRCm39) N2031S probably damaging Het
Col7a1 T C 9: 108,794,989 (GRCm39) probably benign Het
Dbr1 A G 9: 99,466,072 (GRCm39) probably null Het
Dip2b T C 15: 100,100,233 (GRCm39) L1267P probably damaging Het
Dolk A G 2: 30,175,586 (GRCm39) M153T probably benign Het
Duxf1 C T 10: 58,060,704 (GRCm39) E17K possibly damaging Het
Duxf1 G A 10: 58,060,136 (GRCm39) probably benign Het
Duxf1 A G 10: 58,059,276 (GRCm39) C493R probably benign Het
Duxf3 A C 10: 58,067,498 (GRCm39) S27A probably benign Het
Eef1d C T 15: 75,775,581 (GRCm39) R26H probably benign Homo
Efcab5 C T 11: 77,028,517 (GRCm39) Het
Epc1 T C 18: 6,449,246 (GRCm39) D467G probably damaging Het
Fancm T G 12: 65,152,196 (GRCm39) M884R probably benign Het
Fbxo24 G T 5: 137,620,164 (GRCm39) H15N probably damaging Het
Frem1 A G 4: 82,924,045 (GRCm39) F305L probably damaging Het
Fstl5 A G 3: 76,567,006 (GRCm39) D550G probably damaging Het
Gcnt3 T G 9: 69,941,326 (GRCm39) K414T possibly damaging Het
Gm10718 A T 9: 3,024,417 (GRCm39) T134S probably benign Het
Gm10722 A G,C 9: 3,001,414 (GRCm39) probably benign Het
Gm10800 T C 2: 98,497,163 (GRCm39) R152G probably benign Homo
Gm10800 C A 2: 98,497,250 (GRCm39) V123F probably benign Homo
Gm10800 A C 2: 98,496,893 (GRCm39) F220C probably benign Het
Gm10801 A G 2: 98,492,648 (GRCm39) R23G probably benign Homo
Gm11168 C T 9: 3,004,605 (GRCm39) P49S probably benign Het
Gm21738 G A 14: 19,417,330 (GRCm38) S66L probably benign Het
Hjurp TCTGGGAGGGCTTGCTCCGGGGGCAGTGTGTCCTGTTCTTGTGCAGCCCCTG T 1: 88,194,000 (GRCm39) probably benign Het
Hmgcr A G 13: 96,795,562 (GRCm39) Y336H probably damaging Het
Hoxa13 G C 6: 52,260,648 (GRCm38) probably benign Homo
Hoxa13 C G 6: 52,260,647 (GRCm38) probably benign Homo
Igf2bp3 A C 6: 49,094,084 (GRCm39) probably null Het
Kcnb2 A T 1: 15,383,200 (GRCm39) K175N possibly damaging Het
Kdr T C 5: 76,102,631 (GRCm39) probably benign Het
Kif5c A G 2: 49,584,044 (GRCm39) K160E probably damaging Het
Kif7 A T 7: 79,360,817 (GRCm39) V186E probably damaging Het
Krt16 T A 11: 100,139,575 (GRCm39) T48S unknown Het
Liph T C 16: 21,814,119 (GRCm39) M1V probably null Het
Mctp2 A G 7: 71,740,005 (GRCm39) F795S probably damaging Het
Muc4 T A 16: 32,755,699 (GRCm38) probably benign Homo
Muc4 C G 16: 32,755,676 (GRCm38) probably benign Homo
Muc4 T A 16: 32,755,684 (GRCm38) probably benign Homo
Myo15a G T 11: 60,373,953 (GRCm39) A1267S probably damaging Het
Myo15a T C 11: 60,386,280 (GRCm39) Y1802H probably damaging Het
Myo7b G A 18: 32,094,259 (GRCm39) T1963I probably benign Het
Nadk2 TG T 15: 9,100,232 (GRCm39) probably null Homo
Naip5 T C 13: 100,356,268 (GRCm39) N1116D probably benign Het
Naip5 T C 13: 100,356,247 (GRCm39) R1123G probably benign Het
Nap1l1 A G 10: 111,322,583 (GRCm39) D61G probably null Het
Napsa A T 7: 44,230,875 (GRCm39) T81S probably damaging Het
Ngp T C 9: 110,251,337 (GRCm39) probably benign Het
Nktr T A 9: 121,570,687 (GRCm39) V143E probably damaging Het
Obscn A G 11: 58,957,890 (GRCm39) probably null Het
Or10ag53 G A 2: 87,082,973 (GRCm39) A231T probably benign Het
Or11i1 T C 3: 106,729,282 (GRCm39) I198V probably benign Het
Or4f56 G A 2: 111,703,649 (GRCm39) L184F probably benign Het
Or52ab2 C T 7: 102,970,076 (GRCm39) R153* probably null Het
Or52d3 G A 7: 104,229,237 (GRCm39) R128Q probably damaging Het
Or6p1 A G 1: 174,258,390 (GRCm39) Y132C probably damaging Het
Paip2b A G 6: 83,785,823 (GRCm39) Y136H probably damaging Het
Pde2a G T 7: 101,160,361 (GRCm39) R845L probably damaging Het
Pgap2 A G 7: 101,886,405 (GRCm39) Y197C possibly damaging Het
Phf11b A G 14: 59,560,611 (GRCm39) probably benign Het
Pitpnm2 A T 5: 124,269,178 (GRCm39) D481E probably benign Het
Pxk A T 14: 8,152,130 (GRCm38) H482L probably benign Het
Rad50 A G 11: 53,585,726 (GRCm39) probably null Het
Rbmyf1 T A Y: 2,787,132 (GRCm39) N228Y probably benign Het
Rbmyf5 T C Y: 3,297,411 (GRCm39) H235R probably benign Het
Rbmyf6 C T Y: 3,328,944 (GRCm39) A241T possibly damaging Het
Rnf220 A G 4: 117,134,566 (GRCm39) probably null Het
Saxo5 T A 8: 3,526,062 (GRCm39) S72T possibly damaging Het
Selenbp1 C T 3: 94,844,607 (GRCm39) T88M probably damaging Het
Sft2d1 T C 17: 8,609,863 (GRCm39) I104T possibly damaging Het
Sik1 A G 17: 32,070,305 (GRCm39) S135P probably damaging Het
Slc16a3 T C 11: 120,846,172 (GRCm39) F34L probably damaging Het
Slc6a20b T C 9: 123,612,126 (GRCm38) N85S probably benign Homo
Snrnp27 T C 6: 86,659,893 (GRCm39) R34G unknown Het
Sos2 T C 12: 69,664,851 (GRCm39) H393R probably benign Het
Sp110 C T 1: 85,513,971 (GRCm39) R262Q probably benign Het
Sp110 T C 1: 85,513,975 (GRCm39) R261G probably benign Het
Sp140 T A 1: 85,528,893 (GRCm39) Y5N probably benign Het
Sp140 A G 1: 85,570,942 (GRCm39) S461G probably benign Het
Sp140 G C 1: 85,538,603 (GRCm39) K113N probably benign Het
Sp140l1 G A 1: 85,077,341 (GRCm39) A75V probably benign Het
Sp140l2 A C 1: 85,223,395 (GRCm39) probably benign Het
Speer4a2 A T 5: 26,291,485 (GRCm39) F107Y probably benign Het
Speer4a2 C G 5: 26,294,093 (GRCm39) W28C probably damaging Het
Ssrp1 G A 2: 84,868,760 (GRCm39) V40M probably damaging Het
Tada2a T C 11: 83,970,563 (GRCm39) E202G probably damaging Het
Tcf20 C A 15: 82,735,785 (GRCm39) A1889S probably damaging Het
Tdrd12 A T 7: 35,180,528 (GRCm39) Y828* probably null Het
Tlr2 T A 3: 83,745,756 (GRCm39) D109V probably benign Het
Tomm40 G A 7: 19,437,016 (GRCm39) T17M probably damaging Het
Tsga10ip T C 19: 5,440,161 (GRCm39) T135A possibly damaging Het
Tspan8 G A 10: 115,653,515 (GRCm39) V4M probably damaging Het
Ttc28 A T 5: 111,040,719 (GRCm39) T36S probably benign Het
Ugt1a6b G A 1: 88,146,112 (GRCm39) R519Q probably damaging Het
Ugt1a6b TTCA T 1: 88,143,880 (GRCm39) probably benign Het
Ugt1a6b G A 1: 88,143,976 (GRCm39) A199T probably damaging Het
Unc45a A G 7: 79,976,109 (GRCm39) M790T possibly damaging Het
Vav3 T C 3: 109,571,751 (GRCm39) probably null Het
Vcpkmt G A 12: 69,629,552 (GRCm39) S70L probably benign Het
Vmn1r3 C T 4: 3,184,691 (GRCm39) M205I probably damaging Het
Vmn1r3 C T 4: 3,184,774 (GRCm39) V178I probably benign Het
Vmn2r66 T C 7: 84,644,301 (GRCm39) Q703R probably damaging Het
Vmn2r98 G T 17: 19,301,223 (GRCm39) V742F probably benign Het
Wfdc8 A G 2: 164,439,696 (GRCm39) S229P possibly damaging Het
Xpo4 A T 14: 57,822,068 (GRCm39) C1083S probably null Het
Zbtb38 T C 9: 96,568,369 (GRCm39) D905G probably damaging Het
Zbtb8b A G 4: 129,321,308 (GRCm39) *518Q probably null Het
Zfp600 TC T 4: 146,131,802 (GRCm39) probably null Het
Zfp992 C T 4: 146,550,569 (GRCm39) P97S 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
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
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'- GGTTTTCTTCCAATTCTCAGAGTCAG -3'
(R):5'- AAAGAGACACCCATTGCCGG -3'

Sequencing Primer
(F):5'- TGCCAGAAGGACTTAGAC -3'
(R):5'- ATTGCCGGCAATGGGTG -3'
Posted On 2018-06-12