Mutagenetix > Incidental Mutation

Incidental Mutation 'R4870:Knl1'

376477

Institutional Source

Beutler Lab

Gene Symbol

Knl1

Ensembl Gene

ENSMUSG00000027326

Gene Name

kinetochore scaffold 1

Synonyms

Casc5, 2310043D08Rik, 5730505K17Rik

MMRRC Submission

042480-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4870 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

118877600-118935982 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 118911994 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 1704 (T1704A)

Ref Sequence

ENSEMBL: ENSMUSP00000097140 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028802] [ENSMUST00000099542]

AlphaFold

Q66JQ7

Predicted Effect

probably benign
Transcript: ENSMUST00000028802
AA Change: T1704A

PolyPhen 2 Score 0.220 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000028802
Gene: ENSMUSG00000027326
AA Change: T1704A

Domain	Start	End	E-Value	Type
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: T1704A

PolyPhen 2 Score 0.220 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000097140
Gene: ENSMUSG00000027326
AA Change: T1704A

Domain	Start	End	E-Value	Type
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

Meta Mutation Damage Score

0.0638

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 96.9%
20x: 94.1%

Validation Efficiency

100% (77/77)

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: 68 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb11	A	T	2: 69,069,540 (GRCm39)	I1285N	probably damaging	Het
Abcc8	G	A	7: 45,756,683 (GRCm39)	R721*	probably null	Het
Alox8	T	C	11: 69,077,394 (GRCm39)	Y423C	probably damaging	Het
Ankle2	T	A	5: 110,399,344 (GRCm39)		probably null	Het
Cdc14a	A	G	3: 116,217,109 (GRCm39)	I9T	probably benign	Het
Ceacam18	T	C	7: 43,291,328 (GRCm39)	C257R	probably damaging	Het
Cilp	T	C	9: 65,186,980 (GRCm39)	V1025A	probably damaging	Het
Clcn7	G	T	17: 25,372,539 (GRCm39)		probably benign	Het
Csnk1d	A	T	11: 120,874,014 (GRCm39)		probably benign	Het
Cyp11b2	A	G	15: 74,724,995 (GRCm39)	S285P	probably benign	Het
Dip2b	T	A	15: 100,093,665 (GRCm39)		probably null	Het
Dmrt1	T	A	19: 25,483,219 (GRCm39)	M1K	probably null	Het
Dnajc14	T	C	10: 128,653,219 (GRCm39)	V684A	probably benign	Het
Dnmt3b	A	G	2: 153,512,284 (GRCm39)	Q335R	probably benign	Het
Exoc3l2	T	A	7: 19,229,117 (GRCm39)	C772S	unknown	Het
F2rl1	A	T	13: 95,650,492 (GRCm39)	F130Y	probably damaging	Het
Galk2	C	G	2: 125,771,557 (GRCm39)	S194*	probably null	Het
Garre1	C	A	7: 33,984,312 (GRCm39)	V104L	possibly damaging	Het
Gpbp1l1	A	G	4: 116,430,714 (GRCm39)	T62A	probably benign	Het
H2-Q10	A	T	17: 35,781,357 (GRCm39)	D53V	probably damaging	Het
H2-T22	T	C	17: 36,349,924 (GRCm39)	K356R	probably benign	Het
Insrr	G	A	3: 87,718,911 (GRCm39)	V956M	probably damaging	Het
Ints7	A	G	1: 191,328,443 (GRCm39)	T239A	probably damaging	Het
Isl1	A	G	13: 116,444,806 (GRCm39)		probably benign	Het
Kcng2	A	G	18: 80,366,083 (GRCm39)	C90R	probably benign	Het
Kif3c	C	T	12: 3,451,735 (GRCm39)	P171S	probably damaging	Het
Lats1	A	G	10: 7,581,549 (GRCm39)	Y778C	probably damaging	Het
Limd2	T	C	11: 106,050,215 (GRCm39)	M1V	probably null	Het
Mcm10	A	T	2: 5,008,970 (GRCm39)	I333N	probably damaging	Het
Mipep	T	A	14: 61,040,329 (GRCm39)	L283*	probably null	Het
Mixl1	A	G	1: 180,522,237 (GRCm39)	S215P	probably benign	Het
Mmp21	A	G	7: 133,280,406 (GRCm39)	L188P	probably damaging	Het
Mob1a	T	C	6: 83,317,221 (GRCm39)	S213P	probably benign	Het
Mplkipl1	C	T	19: 61,164,364 (GRCm39)	G24R	unknown	Het
Ndufaf6	T	C	4: 11,060,917 (GRCm39)	T220A	probably benign	Het
Nr4a3	A	T	4: 48,051,651 (GRCm39)	Y135F	possibly damaging	Het
Ntn1	CCTTCTTCT	CCTTCT	11: 68,103,852 (GRCm39)		probably benign	Het
Obscn	A	T	11: 59,027,032 (GRCm39)	L57Q	probably damaging	Het
Or52e19b	T	A	7: 103,032,840 (GRCm39)	D123V	probably damaging	Het
Or5d35	T	C	2: 87,855,804 (GRCm39)	L246P	probably damaging	Het
Pirb	T	A	7: 3,715,661 (GRCm39)	M839L	probably benign	Het
Plcl2	A	G	17: 50,914,254 (GRCm39)	E421G	possibly damaging	Het
Ppp1r12b	T	C	1: 134,876,771 (GRCm39)	N99S	probably benign	Het
Ptpro	A	G	6: 137,354,130 (GRCm39)	K169E	probably damaging	Het
Rita1	T	A	5: 120,749,448 (GRCm39)	K88N	probably damaging	Het
Rptn	A	T	3: 93,303,776 (GRCm39)	K370*	probably null	Het
Simc1	A	G	13: 54,687,576 (GRCm39)	D115G	probably null	Het
Stab1	T	A	14: 30,864,000 (GRCm39)	N136I	probably benign	Het
Syt4	T	A	18: 31,580,409 (GRCm39)		probably benign	Het
Sytl2	A	T	7: 90,038,106 (GRCm39)	N522I	probably damaging	Het
Tax1bp1	A	G	6: 52,706,478 (GRCm39)		probably benign	Het
Tenm2	A	T	11: 35,969,396 (GRCm39)	D847E	probably damaging	Het
Th	G	T	7: 142,447,834 (GRCm39)	D321E	probably benign	Het
Tmem44	A	T	16: 30,359,591 (GRCm39)	L46Q	probably damaging	Het
Trp53bp1	A	G	2: 121,087,122 (GRCm39)	L178P	probably damaging	Het
Trp63	A	G	16: 25,684,968 (GRCm39)	*285W	probably null	Het
Tsen34	T	C	7: 3,697,380 (GRCm39)		probably benign	Het
Tssk4	C	T	14: 55,889,272 (GRCm39)	T256I	probably benign	Het
Ttc17	A	T	2: 94,196,954 (GRCm39)	N464K	probably damaging	Het
Ttll2	C	T	17: 7,618,998 (GRCm39)	V310I	probably benign	Het
Ubn1	A	G	16: 4,895,177 (GRCm39)	E741G	probably damaging	Het
Urad	T	A	5: 147,252,264 (GRCm39)	I63F	probably damaging	Het
Vcan	T	C	13: 89,852,858 (GRCm39)	T701A	probably benign	Het
Vmn2r58	A	G	7: 41,486,639 (GRCm39)	V752A	possibly damaging	Het
Vmn2r69	C	A	7: 85,060,793 (GRCm39)	V264L	possibly damaging	Het
Zfp292	A	G	4: 34,808,917 (GRCm39)	S1376P	probably damaging	Het
Zfp955a	G	A	17: 33,460,699 (GRCm39)	R478*	probably null	Het
Znfx1	A	C	2: 166,897,189 (GRCm39)	F578L	probably benign	Het

Other mutations in Knl1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
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
R6419:Knl1	UTSW	2	118,899,484 (GRCm39)	missense	probably benign	0.02
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'- TGGTTCTCCCAGACATGGTGTC -3'
(R):5'- GTAGACAGAACTGGGTTTCTTTTC -3'

Sequencing Primer
(F):5'- TGTCACAGCGTGGCAAG -3'
(R):5'- CATTACAGATGGTTGTGAGCCACC -3'

Posted On

2016-03-17