Mutagenetix > Incidental Mutation

Incidental Mutation 'R7475:Knl1'

579392

Institutional Source

Beutler Lab

Gene Symbol

Knl1

Ensembl Gene

ENSMUSG00000027326

Gene Name

kinetochore scaffold 1

Synonyms

Casc5, 2310043D08Rik, 5730505K17Rik

MMRRC Submission

045549-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7475 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

118877600-118935982 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 118918027 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Leucine at position 1795 (H1795L)

Ref Sequence

ENSEMBL: ENSMUSP00000028802 (fasta)

Gene Model

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

AlphaFold

Q66JQ7

Predicted Effect

probably damaging
Transcript: ENSMUST00000028802
AA Change: H1795L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000028802
Gene: ENSMUSG00000027326
AA Change: H1795L

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 damaging
Transcript: ENSMUST00000099542
AA Change: H1795L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000097140
Gene: ENSMUSG00000027326
AA Change: H1795L

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

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 98.9%

Validation Efficiency

99% (77/78)

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: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc5	G	T	16: 20,218,739 (GRCm39)	N214K	probably benign	Het
Abcf1	A	G	17: 36,274,459 (GRCm39)		probably null	Het
Agxt2	A	T	15: 10,409,623 (GRCm39)	M508L	probably benign	Het
Akr1c21	A	T	13: 4,626,318 (GRCm39)	Y114F	probably benign	Het
Amz1	T	C	5: 140,729,941 (GRCm39)		probably null	Het
Ank1	G	T	8: 23,622,646 (GRCm39)	A1732S	probably benign	Het
Atg16l1	T	C	1: 87,687,805 (GRCm39)	S50P	possibly damaging	Het
AW551984	A	G	9: 39,509,236 (GRCm39)	S302P	probably damaging	Het
Ccn6	T	A	10: 39,034,296 (GRCm39)	Y102F	probably damaging	Het
Ces3a	T	A	8: 105,780,322 (GRCm39)		probably null	Het
Dedd	C	A	1: 171,167,881 (GRCm39)	P185Q	probably benign	Het
Fam186a	A	T	15: 99,845,395 (GRCm39)	V283E	unknown	Het
Fat2	C	A	11: 55,194,479 (GRCm39)	V1187F	probably benign	Het
Fbxw11	T	C	11: 32,661,999 (GRCm39)		probably null	Het
Fcgbp	C	T	7: 27,802,401 (GRCm39)	T1443I	probably damaging	Het
Foxj2	A	G	6: 122,814,801 (GRCm39)	D279G	probably benign	Het
Gbp5	A	G	3: 142,207,122 (GRCm39)	D97G	probably damaging	Het
Gm49368	A	T	7: 127,707,154 (GRCm39)	T661S	possibly damaging	Het
Gria4	T	G	9: 4,513,330 (GRCm39)	T260P	probably damaging	Het
Gtf2ird2	T	A	5: 134,230,267 (GRCm39)	D195E	possibly damaging	Het
Hectd4	T	A	5: 121,496,196 (GRCm39)		probably null	Het
Ifngr2	G	A	16: 91,354,797 (GRCm39)	C32Y	unknown	Het
Ikzf5	A	T	7: 130,993,788 (GRCm39)	C280S	probably benign	Het
Ints9	G	T	14: 65,263,914 (GRCm39)	E395D	probably null	Het
Isoc2b	T	C	7: 4,854,084 (GRCm39)	D96G	probably benign	Het
Jmjd1c	T	G	10: 67,061,092 (GRCm39)	S967R	probably benign	Het
Kcnj3	A	T	2: 55,327,338 (GRCm39)	K42N	probably benign	Het
Kiz	T	C	2: 146,733,006 (GRCm39)	V394A	possibly damaging	Het
Lmntd2	A	G	7: 140,790,602 (GRCm39)		probably null	Het
Loxhd1	C	A	18: 77,500,001 (GRCm39)	D1690E	possibly damaging	Het
Lrp1b	T	C	2: 41,234,588 (GRCm39)	D1121G		Het
Map3k2	T	C	18: 32,333,015 (GRCm39)	V63A	possibly damaging	Het
Mcc	G	T	18: 44,609,303 (GRCm39)	A499D	probably damaging	Het
Mcpt9	T	A	14: 56,264,400 (GRCm39)	I232F	probably damaging	Het
Meltf	A	G	16: 31,700,756 (GRCm39)	K92R	probably benign	Het
Mff	T	A	1: 82,723,159 (GRCm39)		probably null	Het
Mrgpra3	T	A	7: 47,239,695 (GRCm39)	Y77F	probably damaging	Het
Mylk	G	A	16: 34,734,446 (GRCm39)		probably null	Het
Ndufv2	A	G	17: 66,394,532 (GRCm39)	V111A	possibly damaging	Het
Nkd2	T	C	13: 73,973,861 (GRCm39)	E99G	probably damaging	Het
Nlk	C	A	11: 78,474,225 (GRCm39)	G358V	probably damaging	Het
Nnmt	A	T	9: 48,503,532 (GRCm39)	C165S	probably damaging	Het
Nxpe4	T	A	9: 48,304,640 (GRCm39)	C242*	probably null	Het
Oas1b	A	T	5: 120,955,705 (GRCm39)	N162I	probably damaging	Het
Or4s2	A	G	2: 88,473,554 (GRCm39)	I148V	probably benign	Het
Otog	A	G	7: 45,916,700 (GRCm39)	N879S	probably damaging	Het
Pcsk7	T	A	9: 45,838,923 (GRCm39)	Y612N	probably damaging	Het
Peg10	CCACATCAGGATCCACATCAGGATGCACATCAGCATCAGGATCCCCATCAGGATGCACATCAGGATCCACATCAGGATGCACATCAG	CCACATCAGGATCCACATCAGGATGCACATCAG	6: 4,756,398 (GRCm39)		probably benign	Het
Pgbd5	T	C	8: 125,160,750 (GRCm39)	D39G	probably benign	Het
Pkhd1l1	C	T	15: 44,368,581 (GRCm39)	Q800*	probably null	Het
Pkn3	T	C	2: 29,977,122 (GRCm39)	S621P	probably benign	Het
Polr3c	T	C	3: 96,622,501 (GRCm39)	I385V	probably benign	Het
Ppp1r21	G	T	17: 88,863,031 (GRCm39)	G257W	probably benign	Het
Prkn	A	G	17: 11,653,501 (GRCm39)	D199G	probably benign	Het
Pxylp1	C	T	9: 96,738,420 (GRCm39)		probably null	Het
Rasgrp1	T	C	2: 117,116,589 (GRCm39)	T613A	probably benign	Het
Robo3	C	T	9: 37,336,674 (GRCm39)	V387I	probably benign	Het
Rxfp2	T	A	5: 149,973,046 (GRCm39)	Y174N	possibly damaging	Het
Sec24a	T	C	11: 51,604,379 (GRCm39)	M746V	probably damaging	Het
Sema4f	T	A	6: 82,891,355 (GRCm39)	E571D	possibly damaging	Het
Septin3	T	C	15: 82,170,657 (GRCm39)	V217A	probably benign	Het
Serpinb1b	A	C	13: 33,277,548 (GRCm39)	K260N	probably benign	Het
Sin3b	A	G	8: 73,476,500 (GRCm39)	T645A	possibly damaging	Het
Sobp	C	T	10: 42,897,830 (GRCm39)	R585Q	probably damaging	Het
Specc1l	T	A	10: 75,082,281 (GRCm39)	L559Q	possibly damaging	Het
Srxn1	C	T	2: 151,947,573 (GRCm39)		probably benign	Het
Sspo	G	A	6: 48,432,794 (GRCm39)	R890Q	probably benign	Het
Stard9	A	G	2: 120,518,591 (GRCm39)	D505G	probably damaging	Het
Tjp1	A	T	7: 64,972,087 (GRCm39)	I653K	probably damaging	Het
Tnks	C	T	8: 35,298,866 (GRCm39)	E1296K	probably damaging	Het
Ttbk2	A	T	2: 120,579,121 (GRCm39)	I667N	probably benign	Het
Usp24	T	C	4: 106,199,550 (GRCm39)	S165P	possibly damaging	Het
Usp46	T	A	5: 74,189,598 (GRCm39)	K109*	probably null	Het
Vmn1r191	A	G	13: 22,362,942 (GRCm39)	C271R	probably benign	Het
Zfp592	T	C	7: 80,673,200 (GRCm39)	S55P	probably damaging	Het
Zmynd15	T	C	11: 70,351,867 (GRCm39)	S158P	probably benign	Het
Zscan22	T	G	7: 12,640,664 (GRCm39)	C303G	probably damaging	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
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
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
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'- TCTAGATTAGGCAAAACCCAGC -3'
(R):5'- ACAACATGTGAGACATAGGCC -3'

Sequencing Primer
(F):5'- GCACAGGCAATTGAACTCG -3'
(R):5'- GTGCCAAAACCTGAAGCTTCTG -3'

Posted On

2019-10-07