Mutagenetix > Incidental Mutation

Incidental Mutation 'R7559:Knl1'

584926

Institutional Source

Beutler Lab

Gene Symbol

Knl1

Ensembl Gene

ENSMUSG00000027326

Gene Name

kinetochore scaffold 1

Synonyms

Casc5, 2310043D08Rik, 5730505K17Rik

MMRRC Submission

045653-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7559 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

118877600-118935982 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 118924487 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Glycine at position 1840 (E1840G)

Ref Sequence

ENSEMBL: ENSMUSP00000028802 (fasta)

Gene Model

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

AlphaFold

Q66JQ7

Predicted Effect

possibly damaging
Transcript: ENSMUST00000028802
AA Change: E1840G

PolyPhen 2 Score 0.842 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000028802
Gene: ENSMUSG00000027326
AA Change: E1840G

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

possibly damaging
Transcript: ENSMUST00000099542
AA Change: E1840G

PolyPhen 2 Score 0.842 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000097140
Gene: ENSMUSG00000027326
AA Change: E1840G

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: 99.9%
10x: 99.6%
20x: 98.9%

Validation Efficiency

99% (68/69)

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: 72 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adap1	C	A	5: 139,265,295 (GRCm39)	R206L	probably damaging	Het
Adcy3	A	G	12: 4,248,440 (GRCm39)	K501E	probably benign	Het
Agl	T	C	3: 116,545,764 (GRCm39)	D679G		Het
Ankrd10	A	T	8: 11,662,548 (GRCm39)	V395D	probably damaging	Het
Ano5	A	G	7: 51,224,636 (GRCm39)	I531V	probably damaging	Het
Apol9a	T	A	15: 77,288,761 (GRCm39)	H202L	possibly damaging	Het
Atp6v1c2	A	C	12: 17,351,215 (GRCm39)	I105M	probably benign	Het
Cfap57	C	T	4: 118,472,128 (GRCm39)	V84I	probably benign	Het
Coro1b	T	C	19: 4,200,220 (GRCm39)		probably null	Het
D930020B18Rik	A	G	10: 121,492,131 (GRCm39)		probably benign	Het
Dcst2	T	C	3: 89,276,021 (GRCm39)	F384S	possibly damaging	Het
Ddx39a	T	A	8: 84,447,595 (GRCm39)	F147I	possibly damaging	Het
Drosha	A	G	15: 12,842,508 (GRCm39)	E393G	probably damaging	Het
Etfdh	T	C	3: 79,530,886 (GRCm39)	Y45C	probably damaging	Het
Fam20c	G	T	5: 138,778,954 (GRCm39)	E287D	possibly damaging	Het
Flnc	T	A	6: 29,459,009 (GRCm39)	D2463E	probably damaging	Het
Flt4	A	T	11: 49,535,198 (GRCm39)	I1209F	possibly damaging	Het
Foxp1	T	C	6: 98,922,521 (GRCm39)	D437G	unknown	Het
Fras1	T	C	5: 96,888,713 (GRCm39)	V2753A	possibly damaging	Het
Ftsj3	T	C	11: 106,143,813 (GRCm39)	D277G	possibly damaging	Het
Gad1	T	C	2: 70,394,256 (GRCm39)		probably null	Het
Gal3st2c	A	G	1: 93,937,075 (GRCm39)	Y340C	probably damaging	Het
Gbp9	A	G	5: 105,232,975 (GRCm39)	F226L	probably damaging	Het
Gm11992	C	T	11: 9,002,747 (GRCm39)	P37S	possibly damaging	Het
Gm19668	G	T	10: 77,634,572 (GRCm39)	C132*	probably null	Het
Hdac3	A	T	18: 38,078,569 (GRCm39)	F139I	possibly damaging	Het
Hectd4	A	G	5: 121,453,573 (GRCm39)		probably null	Het
Helz	T	A	11: 107,491,104 (GRCm39)	S162T	possibly damaging	Het
Hspb6	C	A	7: 30,253,712 (GRCm39)	S75Y	probably damaging	Het
Il17rb	T	A	14: 29,719,000 (GRCm39)	I361F	probably damaging	Het
Iqsec3	A	T	6: 121,364,739 (GRCm39)	V850D	probably damaging	Het
Lamc3	A	G	2: 31,812,380 (GRCm39)	K939R	probably benign	Het
Lmo7	C	T	14: 102,124,662 (GRCm39)	R496*	probably null	Het
Lsm14a	A	T	7: 34,052,826 (GRCm39)	C374*	probably null	Het
Luc7l	T	C	17: 26,474,089 (GRCm39)	L49P	probably damaging	Het
Mdga2	A	C	12: 66,520,003 (GRCm39)	C988G	probably damaging	Het
Mtf1	T	C	4: 124,713,999 (GRCm39)	V136A	probably damaging	Het
Myo7b	T	A	18: 32,116,413 (GRCm39)	I1016F	probably benign	Het
Nadsyn1	C	A	7: 143,361,804 (GRCm39)	A306S	probably benign	Het
Naip5	T	C	13: 100,356,204 (GRCm39)	Q1137R	probably benign	Het
Naip5	G	T	13: 100,356,205 (GRCm39)	Q1137K	not run	Het
Nr4a1	T	C	15: 101,168,780 (GRCm39)	V272A	probably damaging	Het
Opcml	A	T	9: 28,814,620 (GRCm39)	T291S	probably benign	Het
Or13a24	T	A	7: 140,154,356 (GRCm39)	C97S	probably damaging	Het
Or52u1	C	A	7: 104,237,087 (GRCm39)	H25Q	probably damaging	Het
Or56b1b	C	T	7: 108,164,763 (GRCm39)	A80T	probably damaging	Het
Osbp2	C	G	11: 3,662,493 (GRCm39)	K196N	probably damaging	Het
Otoa	T	C	7: 120,743,149 (GRCm39)	V792A	probably damaging	Het
Pcmtd1	A	G	1: 7,239,766 (GRCm39)	D245G	probably damaging	Het
Pcnx1	T	C	12: 82,039,896 (GRCm39)	V1428A	unknown	Het
Pik3r4	A	G	9: 105,555,352 (GRCm39)	H1103R	probably benign	Het
Pjvk	C	T	2: 76,486,154 (GRCm39)	H185Y	probably benign	Het
Pkd1l3	T	C	8: 110,351,072 (GRCm39)	V639A	probably benign	Het
Pklr	T	C	3: 89,050,365 (GRCm39)	S405P	probably damaging	Het
Pla2g12a	T	A	3: 129,672,569 (GRCm39)	Y68N	probably damaging	Het
Proz	A	G	8: 13,113,455 (GRCm39)	H92R	probably benign	Het
Sec23ip	G	T	7: 128,379,074 (GRCm39)	V844F	possibly damaging	Het
Sema3f	A	G	9: 107,561,777 (GRCm39)	V520A	possibly damaging	Het
Serpinb12	A	G	1: 106,881,453 (GRCm39)	I197V	probably damaging	Het
Sim2	A	T	16: 93,910,218 (GRCm39)	I207F	possibly damaging	Het
Slc15a2	C	T	16: 36,572,259 (GRCm39)	V702I	probably benign	Het
Slc35f4	T	C	14: 49,541,732 (GRCm39)	I341V	probably benign	Het
Spam1	A	G	6: 24,800,452 (GRCm39)	Y397C	probably damaging	Het
Spire1	A	T	18: 67,634,187 (GRCm39)	M417K	probably benign	Het
Srcap	T	C	7: 127,129,722 (GRCm39)	S515P	unknown	Het
Tfrc	T	A	16: 32,440,235 (GRCm39)		probably null	Het
Topors	A	G	4: 40,261,401 (GRCm39)	S628P	unknown	Het
Trim71	T	C	9: 114,342,110 (GRCm39)	Y724C	probably damaging	Het
Ttn	C	T	2: 76,623,199 (GRCm39)	V15413I	probably damaging	Het
Vmn1r21	A	T	6: 57,821,227 (GRCm39)	N72K	probably damaging	Het
Vmn2r80	A	T	10: 79,030,459 (GRCm39)	M762L	probably benign	Het
Wdr62	A	G	7: 29,970,198 (GRCm39)	I203T	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
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
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'- CACTGTCATTAGCTCAGAGTTCAC -3'
(R):5'- GTTAGCTGACCTCTGAAGCTC -3'

Sequencing Primer
(F):5'- AGCTCAGAGTTCACTTATATGATACC -3'
(R):5'- CACCAGGAGAAACTTGAAACATAG -3'

Posted On

2019-10-17