Incidental Mutation 'R6419:Knl1'
ID 540737
Institutional Source Beutler Lab
Gene Symbol Knl1
Ensembl Gene ENSMUSG00000027326
Gene Name kinetochore scaffold 1
Synonyms Casc5, 2310043D08Rik, 5730505K17Rik
MMRRC Submission 044561-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R6419 (G1)
Quality Score 225.009
Status Validated
Chromosome 2
Chromosomal Location 118877600-118935982 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 118899484 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Lysine at position 395 (I395K)
Ref Sequence ENSEMBL: ENSMUSP00000118646 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000028799] [ENSMUST00000028802] [ENSMUST00000099542] [ENSMUST00000152380]
AlphaFold Q66JQ7
Predicted Effect probably benign
Transcript: ENSMUST00000028799
AA Change: I395K

PolyPhen 2 Score 0.022 (Sensitivity: 0.95; Specificity: 0.81)
SMART Domains Protein: ENSMUSP00000028799
Gene: ENSMUSG00000027326
AA Change: I395K

DomainStartEndE-ValueType
low complexity region 49 58 N/A INTRINSIC
PDB:4A1G|H 126 175 1e-13 PDB
low complexity region 426 433 N/A INTRINSIC
low complexity region 883 894 N/A INTRINSIC
low complexity region 1148 1159 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000028802
AA Change: I395K

PolyPhen 2 Score 0.011 (Sensitivity: 0.96; Specificity: 0.78)
SMART Domains Protein: ENSMUSP00000028802
Gene: ENSMUSG00000027326
AA Change: I395K

DomainStartEndE-ValueType
low complexity region 49 58 N/A INTRINSIC
internal_repeat_1 98 304 1.57e-6 PROSPERO
low complexity region 426 433 N/A INTRINSIC
internal_repeat_1 610 824 1.57e-6 PROSPERO
low complexity region 883 894 N/A INTRINSIC
low complexity region 1148 1159 N/A INTRINSIC
low complexity region 1621 1644 N/A INTRINSIC
coiled coil region 1724 1755 N/A INTRINSIC
low complexity region 1836 1850 N/A INTRINSIC
low complexity region 1864 1878 N/A INTRINSIC
PDB:4NF9|B 1899 2119 1e-115 PDB
Predicted Effect probably benign
Transcript: ENSMUST00000099542
AA Change: I395K

PolyPhen 2 Score 0.011 (Sensitivity: 0.96; Specificity: 0.78)
SMART Domains Protein: ENSMUSP00000097140
Gene: ENSMUSG00000027326
AA Change: I395K

DomainStartEndE-ValueType
low complexity region 49 58 N/A INTRINSIC
internal_repeat_1 98 304 1.57e-6 PROSPERO
low complexity region 426 433 N/A INTRINSIC
internal_repeat_1 610 824 1.57e-6 PROSPERO
low complexity region 883 894 N/A INTRINSIC
low complexity region 1148 1159 N/A INTRINSIC
low complexity region 1621 1644 N/A INTRINSIC
coiled coil region 1724 1755 N/A INTRINSIC
low complexity region 1836 1850 N/A INTRINSIC
low complexity region 1864 1878 N/A INTRINSIC
PDB:4NF9|B 1899 2119 1e-115 PDB
Predicted Effect probably benign
Transcript: ENSMUST00000152380
AA Change: I395K

PolyPhen 2 Score 0.022 (Sensitivity: 0.95; Specificity: 0.81)
SMART Domains Protein: ENSMUSP00000118646
Gene: ENSMUSG00000027326
AA Change: I395K

DomainStartEndE-ValueType
low complexity region 49 58 N/A INTRINSIC
PDB:4A1G|H 126 175 3e-14 PDB
low complexity region 426 433 N/A INTRINSIC
Meta Mutation Damage Score 0.1261 question?
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.5%
  • 10x: 97.6%
  • 20x: 92.3%
Validation Efficiency 96% (67/70)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a component of the multiprotein assembly that is required for creation of kinetochore-microtubule attachments and chromosome segregation. The encoded protein functions as a scaffold for proteins that influence the spindle assembly checkpoint during the eukaryotic cell cycle and it interacts with at least five different kinetochore proteins and two checkpoint kinases. In adults, this gene is predominantly expressed in normal testes, various cancer cell lines and primary tumors from other tissues and is ubiquitously expressed in fetal tissues. This gene was originally identified as a fusion partner with the mixed-lineage leukemia (MLL) gene in t(11;15)(q23;q14). Mutations in this gene cause autosomal recessive primary microcephaly-4 (MCPH4). Alternative splicing results in multiple transcript variants encoding different isoforms. Additional splice variants have been described but their biological validity has not been confirmed. [provided by RefSeq, Jan 2013]
PHENOTYPE: Mice homozygous for a transgenic gene disruption exhibit embryonic lethality at E6. Mice homozygous for an ENU-induced allele exhibit possible embryonic lethality. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 69 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930578G10Rik T C 4: 42,812,473 (GRCm39) probably benign Het
Abcc2 T A 19: 43,825,947 (GRCm39) probably null Het
Adamts12 C T 15: 11,215,759 (GRCm39) T260M possibly damaging Het
Adamts20 C T 15: 94,231,556 (GRCm39) V878I possibly damaging Het
Adgrl4 A G 3: 151,144,953 (GRCm39) E34G probably damaging Het
Asah1 A T 8: 41,796,803 (GRCm39) I293N probably damaging Het
Atosa G A 9: 74,916,619 (GRCm39) S413N probably benign Het
B3galt2 A T 1: 143,522,839 (GRCm39) E325V possibly damaging Het
Baz1b T A 5: 135,271,348 (GRCm39) H1310Q probably benign Het
Ccdc125 T A 13: 100,826,834 (GRCm39) N204K probably damaging Het
Cd36 C T 5: 18,002,150 (GRCm39) D284N probably benign Het
Cdh12 T C 15: 21,520,483 (GRCm39) L316S probably damaging Het
Cenpv T C 11: 62,416,008 (GRCm39) K247R probably benign Het
Cldn18 T C 9: 99,574,801 (GRCm39) H257R possibly damaging Het
Cnot8 T A 11: 58,004,891 (GRCm39) Y197N probably damaging Het
Cog3 A T 14: 75,962,178 (GRCm39) C554* probably null Het
Col4a4 A G 1: 82,444,207 (GRCm39) probably null Het
Cops5 G A 1: 10,103,532 (GRCm39) T158I probably damaging Het
Dhh A G 15: 98,792,282 (GRCm39) F242S probably damaging Het
Dot1l T C 10: 80,627,315 (GRCm39) V1512A possibly damaging Het
Dstn T G 2: 143,781,907 (GRCm39) I116S possibly damaging Het
Egfem1 G A 3: 29,711,398 (GRCm39) D326N probably damaging Het
Enpp3 A T 10: 24,684,089 (GRCm39) Y52N probably damaging Het
Gabra2 A G 5: 71,119,426 (GRCm39) S359P probably benign Het
Gbp7 G A 3: 142,252,214 (GRCm39) G599E probably benign Het
Gcat T G 15: 78,920,264 (GRCm39) I198S probably damaging Het
Gm8439 A G 4: 120,466,755 (GRCm39) K82R unknown Het
Grin2b A G 6: 135,717,965 (GRCm39) F709S probably damaging Het
Grm3 T C 5: 9,620,201 (GRCm39) N348D probably damaging Het
Hdgfl1 G A 13: 26,954,075 (GRCm39) probably benign Het
Hmgxb3 G T 18: 61,285,296 (GRCm39) D564E possibly damaging Het
Igkv4-61 C A 6: 69,394,138 (GRCm39) A31S possibly damaging Het
Impg1 A G 9: 80,287,300 (GRCm39) V305A probably benign Het
Ints7 T A 1: 191,334,414 (GRCm39) S313T possibly damaging Het
Lactb2 A T 1: 13,708,459 (GRCm39) Y196* probably null Het
Lad1 T C 1: 135,759,630 (GRCm39) S509P possibly damaging Het
Ltf T C 9: 110,860,090 (GRCm39) F504L possibly damaging Het
Med4 A T 14: 73,751,363 (GRCm39) D104V probably damaging Het
Mrpl58 A T 11: 115,301,073 (GRCm39) N128Y probably damaging Het
Ndufs2 T C 1: 171,068,668 (GRCm39) T54A probably benign Het
Notch2 G T 3: 98,007,705 (GRCm39) probably null Het
Ntng1 A T 3: 109,690,169 (GRCm39) N424K possibly damaging Het
Ntrk2 G A 13: 59,009,113 (GRCm39) W301* probably null Het
Or5b116 T A 19: 13,423,131 (GRCm39) S252T probably benign Het
Otud6b A G 4: 14,822,766 (GRCm39) S113P possibly damaging Het
Pcdhb20 A G 18: 37,638,608 (GRCm39) N378S probably damaging Het
Polr3b T C 10: 84,473,975 (GRCm39) S185P possibly damaging Het
Ptprn G A 1: 75,240,681 (GRCm39) R31C probably benign Het
Rgsl1 C T 1: 153,698,117 (GRCm39) V478M probably damaging Het
Sema6b A T 17: 56,439,784 (GRCm39) L19* probably null Het
Slfn8 A G 11: 82,894,881 (GRCm39) probably null Het
Spen A T 4: 141,203,621 (GRCm39) S1669T unknown Het
Syne2 T C 12: 76,143,740 (GRCm39) F1522L probably damaging Het
Tarbp1 C T 8: 127,185,783 (GRCm39) A470T possibly damaging Het
Tent4a A C 13: 69,658,785 (GRCm39) M350R possibly damaging Het
Tiam1 C A 16: 89,694,912 (GRCm39) E182* probably null Het
Tmem231 G A 8: 112,653,524 (GRCm39) probably benign Het
Trip12 C T 1: 84,771,591 (GRCm39) A186T probably damaging Het
Ufc1 C T 1: 171,116,529 (GRCm39) A147T probably damaging Het
Vmn1r199 A G 13: 22,567,777 (GRCm39) K314R possibly damaging Het
Vmn2r13 A T 5: 109,323,085 (GRCm39) I68K possibly damaging Het
Vmn2r77 A T 7: 86,460,767 (GRCm39) I698F probably damaging Het
Vmn2r86 T C 10: 130,282,795 (GRCm39) K607R probably damaging Het
Vwa3b T C 1: 37,196,457 (GRCm39) V28A probably benign Het
Wdr19 A G 5: 65,373,236 (GRCm39) N166S possibly damaging Het
Wfdc17 G A 11: 83,595,634 (GRCm39) G33R probably damaging Het
Zfp330 T G 8: 83,491,545 (GRCm39) K209N probably benign Het
Zfp493 A G 13: 67,934,526 (GRCm39) T160A probably benign Het
Zfp974 A T 7: 27,610,940 (GRCm39) C262S possibly damaging Het
Other mutations in Knl1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00272:Knl1 APN 2 118,894,564 (GRCm39) missense probably damaging 0.96
IGL00582:Knl1 APN 2 118,932,980 (GRCm39) missense probably benign 0.19
IGL00666:Knl1 APN 2 118,900,945 (GRCm39) missense probably damaging 0.96
IGL01062:Knl1 APN 2 118,907,461 (GRCm39) missense probably benign 0.33
IGL01395:Knl1 APN 2 118,902,047 (GRCm39) missense probably damaging 0.96
IGL01604:Knl1 APN 2 118,900,482 (GRCm39) missense probably damaging 1.00
IGL01996:Knl1 APN 2 118,934,542 (GRCm39) missense probably damaging 1.00
IGL02086:Knl1 APN 2 118,931,255 (GRCm39) missense probably benign 0.40
IGL02105:Knl1 APN 2 118,902,289 (GRCm39) missense probably benign
IGL02106:Knl1 APN 2 118,902,489 (GRCm39) missense possibly damaging 0.89
IGL02201:Knl1 APN 2 118,899,633 (GRCm39) missense probably benign 0.01
IGL02252:Knl1 APN 2 118,903,021 (GRCm39) missense probably damaging 1.00
IGL02414:Knl1 APN 2 118,900,804 (GRCm39) missense possibly damaging 0.83
IGL02655:Knl1 APN 2 118,901,473 (GRCm39) missense possibly damaging 0.62
IGL02682:Knl1 APN 2 118,908,450 (GRCm39) missense possibly damaging 0.86
IGL02710:Knl1 APN 2 118,901,411 (GRCm39) missense probably damaging 0.99
IGL02877:Knl1 APN 2 118,919,312 (GRCm39) missense probably benign 0.08
IGL03100:Knl1 APN 2 118,931,251 (GRCm39) missense probably damaging 0.99
IGL03210:Knl1 APN 2 118,901,098 (GRCm39) missense probably benign 0.02
IGL03138:Knl1 UTSW 2 118,902,840 (GRCm39) missense probably damaging 0.96
R0023:Knl1 UTSW 2 118,933,030 (GRCm39) missense possibly damaging 0.73
R0064:Knl1 UTSW 2 118,906,724 (GRCm39) missense probably benign 0.00
R0064:Knl1 UTSW 2 118,906,724 (GRCm39) missense probably benign 0.00
R0078:Knl1 UTSW 2 118,900,373 (GRCm39) missense probably benign 0.16
R0178:Knl1 UTSW 2 118,888,886 (GRCm39) splice site probably benign
R0295:Knl1 UTSW 2 118,919,320 (GRCm39) missense probably damaging 1.00
R0433:Knl1 UTSW 2 118,934,542 (GRCm39) missense probably damaging 0.96
R0453:Knl1 UTSW 2 118,898,869 (GRCm39) missense probably damaging 1.00
R0569:Knl1 UTSW 2 118,927,916 (GRCm39) missense possibly damaging 0.95
R0827:Knl1 UTSW 2 118,919,382 (GRCm39) splice site probably benign
R0920:Knl1 UTSW 2 118,900,309 (GRCm39) missense probably benign 0.00
R1120:Knl1 UTSW 2 118,892,856 (GRCm39) missense probably damaging 0.99
R1155:Knl1 UTSW 2 118,901,635 (GRCm39) missense possibly damaging 0.90
R1204:Knl1 UTSW 2 118,901,670 (GRCm39) missense probably benign 0.00
R1241:Knl1 UTSW 2 118,903,054 (GRCm39) missense probably benign 0.03
R1387:Knl1 UTSW 2 118,901,211 (GRCm39) missense possibly damaging 0.93
R1448:Knl1 UTSW 2 118,898,788 (GRCm39) missense probably damaging 1.00
R1469:Knl1 UTSW 2 118,901,827 (GRCm39) missense possibly damaging 0.73
R1469:Knl1 UTSW 2 118,901,827 (GRCm39) missense possibly damaging 0.73
R1719:Knl1 UTSW 2 118,902,219 (GRCm39) missense probably benign 0.01
R1721:Knl1 UTSW 2 118,906,815 (GRCm39) missense probably damaging 1.00
R2128:Knl1 UTSW 2 118,902,300 (GRCm39) missense possibly damaging 0.79
R2170:Knl1 UTSW 2 118,918,075 (GRCm39) critical splice donor site probably null
R2227:Knl1 UTSW 2 118,902,481 (GRCm39) missense probably damaging 0.97
R2246:Knl1 UTSW 2 118,902,708 (GRCm39) missense probably damaging 1.00
R2275:Knl1 UTSW 2 118,902,762 (GRCm39) missense probably damaging 0.99
R2508:Knl1 UTSW 2 118,888,849 (GRCm39) nonsense probably null
R3115:Knl1 UTSW 2 118,900,872 (GRCm39) missense possibly damaging 0.53
R3122:Knl1 UTSW 2 118,899,425 (GRCm39) missense probably benign 0.32
R3431:Knl1 UTSW 2 118,892,843 (GRCm39) missense probably damaging 1.00
R3755:Knl1 UTSW 2 118,933,060 (GRCm39) missense probably damaging 1.00
R4461:Knl1 UTSW 2 118,890,080 (GRCm39) missense probably benign 0.00
R4600:Knl1 UTSW 2 118,901,025 (GRCm39) missense possibly damaging 0.90
R4713:Knl1 UTSW 2 118,899,618 (GRCm39) nonsense probably null
R4758:Knl1 UTSW 2 118,902,213 (GRCm39) frame shift probably null
R4762:Knl1 UTSW 2 118,902,417 (GRCm39) missense probably benign 0.01
R4869:Knl1 UTSW 2 118,902,832 (GRCm39) missense possibly damaging 0.73
R4870:Knl1 UTSW 2 118,911,994 (GRCm39) missense probably benign 0.22
R4935:Knl1 UTSW 2 118,899,438 (GRCm39) missense possibly damaging 0.50
R5167:Knl1 UTSW 2 118,900,512 (GRCm39) missense probably damaging 1.00
R5184:Knl1 UTSW 2 118,899,657 (GRCm39) missense probably damaging 1.00
R5293:Knl1 UTSW 2 118,900,176 (GRCm39) missense probably damaging 0.99
R5326:Knl1 UTSW 2 118,898,829 (GRCm39) missense possibly damaging 0.66
R5331:Knl1 UTSW 2 118,900,736 (GRCm39) missense possibly damaging 0.92
R5353:Knl1 UTSW 2 118,901,464 (GRCm39) missense probably benign 0.01
R5493:Knl1 UTSW 2 118,899,211 (GRCm39) missense probably damaging 0.98
R5542:Knl1 UTSW 2 118,898,829 (GRCm39) missense possibly damaging 0.66
R5632:Knl1 UTSW 2 118,900,833 (GRCm39) missense probably damaging 1.00
R5650:Knl1 UTSW 2 118,912,031 (GRCm39) nonsense probably null
R5854:Knl1 UTSW 2 118,900,884 (GRCm39) missense probably benign 0.02
R5979:Knl1 UTSW 2 118,899,841 (GRCm39) missense possibly damaging 0.83
R6086:Knl1 UTSW 2 118,924,549 (GRCm39) missense probably damaging 1.00
R6283:Knl1 UTSW 2 118,900,767 (GRCm39) missense probably damaging 1.00
R6285:Knl1 UTSW 2 118,902,422 (GRCm39) missense probably damaging 1.00
R6313:Knl1 UTSW 2 118,899,799 (GRCm39) missense probably damaging 1.00
R6608:Knl1 UTSW 2 118,917,093 (GRCm39) missense probably damaging 0.99
R6881:Knl1 UTSW 2 118,925,665 (GRCm39) missense possibly damaging 0.67
R7161:Knl1 UTSW 2 118,901,266 (GRCm39) missense possibly damaging 0.79
R7206:Knl1 UTSW 2 118,899,780 (GRCm39) missense probably benign 0.35
R7270:Knl1 UTSW 2 118,933,003 (GRCm39) missense possibly damaging 0.53
R7276:Knl1 UTSW 2 118,902,167 (GRCm39) missense probably damaging 0.98
R7358:Knl1 UTSW 2 118,901,040 (GRCm39) missense possibly damaging 0.92
R7402:Knl1 UTSW 2 118,925,707 (GRCm39) nonsense probably null
R7408:Knl1 UTSW 2 118,901,073 (GRCm39) missense possibly damaging 0.54
R7475:Knl1 UTSW 2 118,918,027 (GRCm39) missense probably damaging 1.00
R7516:Knl1 UTSW 2 118,901,179 (GRCm39) missense probably damaging 0.99
R7524:Knl1 UTSW 2 118,896,460 (GRCm39) missense probably damaging 1.00
R7559:Knl1 UTSW 2 118,924,487 (GRCm39) missense possibly damaging 0.84
R7607:Knl1 UTSW 2 118,925,614 (GRCm39) missense possibly damaging 0.93
R7745:Knl1 UTSW 2 118,902,037 (GRCm39) missense probably benign 0.13
R7847:Knl1 UTSW 2 118,901,457 (GRCm39) missense probably benign 0.02
R8423:Knl1 UTSW 2 118,900,513 (GRCm39) missense probably damaging 1.00
R8725:Knl1 UTSW 2 118,899,524 (GRCm39) missense probably benign 0.34
R8727:Knl1 UTSW 2 118,899,524 (GRCm39) missense probably benign 0.34
R8995:Knl1 UTSW 2 118,902,990 (GRCm39) missense probably benign 0.11
R9023:Knl1 UTSW 2 118,900,761 (GRCm39) missense probably benign 0.27
R9100:Knl1 UTSW 2 118,899,469 (GRCm39) missense probably benign 0.02
R9102:Knl1 UTSW 2 118,917,973 (GRCm39) missense probably benign 0.22
R9303:Knl1 UTSW 2 118,898,829 (GRCm39) missense possibly damaging 0.83
R9400:Knl1 UTSW 2 118,931,224 (GRCm39) missense probably damaging 0.98
R9426:Knl1 UTSW 2 118,899,979 (GRCm39) missense possibly damaging 0.81
R9583:Knl1 UTSW 2 118,887,782 (GRCm39) missense probably damaging 1.00
R9616:Knl1 UTSW 2 118,907,425 (GRCm39) missense probably damaging 1.00
R9616:Knl1 UTSW 2 118,899,994 (GRCm39) missense probably benign 0.02
R9671:Knl1 UTSW 2 118,901,089 (GRCm39) missense probably damaging 1.00
R9766:Knl1 UTSW 2 118,900,381 (GRCm39) missense probably damaging 1.00
R9782:Knl1 UTSW 2 118,899,910 (GRCm39) missense probably benign 0.02
Predicted Primers PCR Primer
(F):5'- ACAGTTGATGGAGCTACAGC -3'
(R):5'- TGGTAATGTCCATGCTATCCTC -3'

Sequencing Primer
(F):5'- TCCAGCTCCAGAGAAGAAAACAG -3'
(R):5'- AAATAGTTTTCTCTCTGAGTGGGCC -3'
Posted On 2018-11-21