Mutagenetix > Incidental Mutation

Incidental Mutation 'R7516:Knl1'

582437

Institutional Source

Beutler Lab

Gene Symbol

Knl1

Ensembl Gene

ENSMUSG00000027326

Gene Name

kinetochore scaffold 1

Synonyms

Casc5, 2310043D08Rik, 5730505K17Rik

MMRRC Submission

045589-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7516 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

118877600-118935982 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 118901179 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 960 (V960A)

Ref Sequence

ENSEMBL: ENSMUSP00000028799 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028799] [ENSMUST00000028802] [ENSMUST00000099542] [ENSMUST00000152380] [ENSMUST00000153300]

AlphaFold

Q66JQ7

Predicted Effect

probably damaging
Transcript: ENSMUST00000028799
AA Change: V960A

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000028799
Gene: ENSMUSG00000027326
AA Change: V960A

Domain	Start	End	E-Value	Type
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 damaging
Transcript: ENSMUST00000028802
AA Change: V960A

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000028802
Gene: ENSMUSG00000027326
AA Change: V960A

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: V960A

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000097140
Gene: ENSMUSG00000027326
AA Change: V960A

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: ENSMUST00000152380

SMART Domains

Protein: ENSMUSP00000118646
Gene: ENSMUSG00000027326

Domain	Start	End	E-Value	Type
low complexity region	49	58	N/A	INTRINSIC
PDB:4A1G\|H	126	175	3e-14	PDB
low complexity region	426	433	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000153300

SMART Domains

Protein: ENSMUSP00000120905
Gene: ENSMUSG00000027326

Domain	Start	End	E-Value	Type
low complexity region	49	58	N/A	INTRINSIC

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.2%

Validation Efficiency

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
Adam28	T	A	14: 68,868,125 (GRCm39)	I407F	probably damaging	Het
Agbl1	A	G	7: 76,075,669 (GRCm39)	Y437C	probably damaging	Het
Alkbh5	T	C	11: 60,429,979 (GRCm39)	V244A	probably damaging	Het
Arap1	T	C	7: 101,058,538 (GRCm39)	F1390L	probably benign	Het
Asph	T	C	4: 9,630,940 (GRCm39)	D136G	possibly damaging	Het
Atp8a2	A	T	14: 60,094,516 (GRCm39)	Y841N	probably damaging	Het
Cald1	A	T	6: 34,686,492 (GRCm39)		probably benign	Het
Capn11	A	G	17: 45,949,766 (GRCm39)	I400T	possibly damaging	Het
Cdh18	T	A	15: 23,259,684 (GRCm39)		probably null	Het
Ces2h	T	A	8: 105,743,458 (GRCm39)	L204Q	probably damaging	Het
Chrna3	G	A	9: 54,922,653 (GRCm39)	A385V	probably benign	Het
Clca4a	A	T	3: 144,672,009 (GRCm39)	L311Q	probably damaging	Het
Clip1	A	G	5: 123,721,448 (GRCm39)	V1149A	probably benign	Het
Clip3	T	A	7: 29,998,268 (GRCm39)	V238D	possibly damaging	Het
Col12a1	A	G	9: 79,520,192 (GRCm39)		probably null	Het
Coro2a	A	G	4: 46,562,992 (GRCm39)	V54A	probably benign	Het
Crem	T	C	18: 3,299,141 (GRCm39)		probably null	Het
Dennd5b	T	C	6: 148,969,878 (GRCm39)	I192V	probably benign	Het
Dst	A	G	1: 34,209,560 (GRCm39)	N1209S	probably benign	Het
Ero1a	T	A	14: 45,525,480 (GRCm39)	M385L	probably benign	Het
Fam13a	A	T	6: 58,932,248 (GRCm39)	V375D	probably damaging	Het
Fgfbp3	T	A	19: 36,896,324 (GRCm39)	Y98F	possibly damaging	Het
Frem3	T	C	8: 81,338,712 (GRCm39)	V335A	probably damaging	Het
Gm19410	T	A	8: 36,263,433 (GRCm39)	D951E	probably benign	Het
Gpatch1	T	C	7: 35,007,625 (GRCm39)	D145G	probably benign	Het
H60c	G	T	10: 3,209,746 (GRCm39)	C180*	probably null	Het
Hmcn1	T	C	1: 150,498,718 (GRCm39)	T4054A	probably benign	Het
Hrg	A	G	16: 22,780,048 (GRCm39)	Y442C	unknown	Het
Hspg2	C	T	4: 137,269,931 (GRCm39)	R2327C	possibly damaging	Het
Klhl31	G	T	9: 77,558,429 (GRCm39)	A382S	probably damaging	Het
Lztr1	C	T	16: 17,327,525 (GRCm39)	A76V	possibly damaging	Het
Me3	G	T	7: 89,497,183 (GRCm39)	E395*	probably null	Het
Morc2b	G	A	17: 33,356,435 (GRCm39)	H446Y	probably benign	Het
Mroh7	A	T	4: 106,548,316 (GRCm39)	M1054K	probably benign	Het
Ms4a6b	T	C	19: 11,506,907 (GRCm39)	V232A	probably benign	Het
Nmt2	C	A	2: 3,313,767 (GRCm39)	D224E	probably damaging	Het
Nox4	C	A	7: 86,970,905 (GRCm39)	R261S	probably benign	Het
Obscn	T	A	11: 59,015,416 (GRCm39)	K1019*	probably null	Het
Or4a15	T	A	2: 89,193,719 (GRCm39)	N18I	probably benign	Het
Or4g7	T	A	2: 111,309,282 (GRCm39)	V51D	probably benign	Het
Or5p67	G	A	7: 107,922,223 (GRCm39)	S220F	probably damaging	Het
Or8k24	C	T	2: 86,216,328 (GRCm39)	V145I	probably benign	Het
Pcdha11	A	T	18: 37,144,671 (GRCm39)	N254I	probably damaging	Het
Pck2	T	A	14: 55,779,913 (GRCm39)	I54N	probably benign	Het
Pkd1l3	T	A	8: 110,361,861 (GRCm39)	W978R	probably damaging	Het
Plxna4	T	C	6: 32,214,703 (GRCm39)	T593A	probably benign	Het
Podn	G	A	4: 107,879,321 (GRCm39)	R266W	probably damaging	Het
Ptpn22	A	G	3: 103,792,854 (GRCm39)	D335G	probably benign	Het
Pxn	A	G	5: 115,644,922 (GRCm39)	D3G	unknown	Het
Rapgefl1	T	G	11: 98,736,960 (GRCm39)	V320G	probably benign	Het
Rel	A	G	11: 23,692,785 (GRCm39)	I416T	probably benign	Het
Sema5b	A	G	16: 35,471,540 (GRCm39)	N378D	probably benign	Het
Sh3bp4	C	A	1: 89,073,368 (GRCm39)	L739M	probably damaging	Het
Skint2	A	T	4: 112,483,168 (GRCm39)	D191V	probably damaging	Het
Slc3a1	T	C	17: 85,371,190 (GRCm39)	Y581H	probably damaging	Het
Smcr8	G	T	11: 60,670,814 (GRCm39)	C654F	probably benign	Het
Spta1	A	C	1: 174,025,349 (GRCm39)	Q738P	probably damaging	Het
Sptlc3	C	A	2: 139,431,438 (GRCm39)	A320D	probably benign	Het
Thnsl2	T	A	6: 71,108,990 (GRCm39)	K274*	probably null	Het
Tmed2	T	A	5: 124,685,055 (GRCm39)	I68K	possibly damaging	Het
Tmtc4	G	A	14: 123,180,735 (GRCm39)	A326V	possibly damaging	Het
Tnks2	T	A	19: 36,849,064 (GRCm39)	S179T	possibly damaging	Het
Trim34b	G	T	7: 103,978,918 (GRCm39)	C55F	probably damaging	Het
Trpm4	T	A	7: 44,954,444 (GRCm39)	E1129V	probably damaging	Het
Tvp23b	T	C	11: 62,782,867 (GRCm39)	S188P	possibly damaging	Het
Usp1	A	G	4: 98,822,356 (GRCm39)	T557A	probably damaging	Het
Vmn2r66	C	T	7: 84,661,176 (GRCm39)	C18Y	possibly damaging	Het
Vmn2r85	T	A	10: 130,254,852 (GRCm39)	T611S	probably damaging	Het
Vps13c	T	C	9: 67,862,289 (GRCm39)	S2969P	possibly damaging	Het
Wdr74	T	A	19: 8,713,554 (GRCm39)	C62*	probably null	Het
Wfikkn1	A	T	17: 26,097,020 (GRCm39)	C435S	probably damaging	Het
Zbtb45	A	T	7: 12,740,269 (GRCm39)	F449I	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
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'- TGCACAAAAGCCTGGATTTC -3'
(R):5'- GGCTTGACAATCGATGAAAACC -3'

Sequencing Primer
(F):5'- TCTGAATGAACTTCTGTCAGGC -3'
(R):5'- AACCGTATGGGATCTGGTGACATC -3'

Posted On

2019-10-17