Mutagenetix > Incidental Mutation

Incidental Mutation 'R5493:Knl1'

432151

Institutional Source

Beutler Lab

Gene Symbol

Knl1

Ensembl Gene

ENSMUSG00000027326

Gene Name

kinetochore scaffold 1

Synonyms

Casc5, 2310043D08Rik, 5730505K17Rik

MMRRC Submission

043054-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5493 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

118877600-118935982 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 118899211 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Lysine at position 304 (I304K)

Ref Sequence

ENSEMBL: ENSMUSP00000118646 (fasta)

Gene Model

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

AlphaFold

Q66JQ7

Predicted Effect

probably damaging
Transcript: ENSMUST00000028799
AA Change: I304K

PolyPhen 2 Score 0.975 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000028799
Gene: ENSMUSG00000027326
AA Change: I304K

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

possibly damaging
Transcript: ENSMUST00000028802
AA Change: I304K

PolyPhen 2 Score 0.929 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000028802
Gene: ENSMUSG00000027326
AA Change: I304K

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: I304K

PolyPhen 2 Score 0.929 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000097140
Gene: ENSMUSG00000027326
AA Change: I304K

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: ENSMUST00000152380
AA Change: I304K

PolyPhen 2 Score 0.975 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000118646
Gene: ENSMUSG00000027326
AA Change: I304K

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

Meta Mutation Damage Score

0.6467

Coding Region Coverage

1x: 98.3%
3x: 97.3%
10x: 95.1%
20x: 90.4%

Validation Efficiency

99% (80/81)

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: 67 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2510009E07Rik	A	G	16: 21,471,993 (GRCm39)	S236P	possibly damaging	Het
A830018L16Rik	C	T	1: 11,615,431 (GRCm39)	R135C	probably damaging	Het
Agpat3	A	G	10: 78,120,069 (GRCm39)	V155A	possibly damaging	Het
Aldh18a1	C	T	19: 40,539,734 (GRCm39)	R747Q	probably damaging	Het
Aloxe3	A	T	11: 69,019,443 (GRCm39)	R119*	probably null	Het
Asap1	A	G	15: 64,002,000 (GRCm39)	V460A	possibly damaging	Het
Bicral	C	A	17: 47,112,620 (GRCm39)	R860L	possibly damaging	Het
Cd180	T	A	13: 102,842,649 (GRCm39)	I565N	probably benign	Het
Cdk13	T	C	13: 17,978,147 (GRCm39)		probably benign	Het
Cdkn2d	T	C	9: 21,200,303 (GRCm39)	D156G	probably benign	Het
Clrn1	A	G	3: 58,753,837 (GRCm39)	S175P	probably damaging	Het
Coro7	A	G	16: 4,450,351 (GRCm39)	L535S	probably damaging	Het
Cse1l	A	G	2: 166,783,110 (GRCm39)		probably benign	Het
Cyp2a12	T	C	7: 26,728,550 (GRCm39)	L7P	unknown	Het
D130043K22Rik	A	G	13: 25,047,586 (GRCm39)	Y377C	probably damaging	Het
Dctn1	G	T	6: 83,159,546 (GRCm39)	R8L	possibly damaging	Het
Duox2	T	C	2: 122,111,977 (GRCm39)	Q1341R	probably damaging	Het
Eif2b3	A	G	4: 116,943,919 (GRCm39)	D447G	possibly damaging	Het
Eif4a3l1	C	G	6: 136,306,555 (GRCm39)	R339G	probably damaging	Het
Fbxw25	T	C	9: 109,481,984 (GRCm39)	Y234C	probably benign	Het
Gcnt2	A	G	13: 41,107,076 (GRCm39)	N315S	possibly damaging	Het
Gm20730	A	T	6: 43,058,746 (GRCm39)	V22E	possibly damaging	Het
Gm4847	T	A	1: 166,457,890 (GRCm39)	I488F	probably damaging	Het
Gmds	A	T	13: 32,124,488 (GRCm39)	M290K	probably benign	Het
Gtf3c1	T	C	7: 125,269,716 (GRCm39)	N699S	probably damaging	Het
Hk3	A	G	13: 55,158,984 (GRCm39)	V479A	probably damaging	Het
Ifnlr1	G	A	4: 135,432,877 (GRCm39)	V438M	probably benign	Het
Il12rb1	C	A	8: 71,262,483 (GRCm39)	P26T	probably benign	Het
Il4i1	G	T	7: 44,489,477 (GRCm39)	R414L	possibly damaging	Het
Ipo4	T	C	14: 55,868,327 (GRCm39)	N490S	probably benign	Het
Kcnmb2	A	G	3: 32,252,291 (GRCm39)	E164G	probably damaging	Het
Kcns1	G	A	2: 164,009,899 (GRCm39)	L287F	probably benign	Het
Kdm1a	ACC	AC	4: 136,284,732 (GRCm39)		probably null	Het
Klk14	G	A	7: 43,341,501 (GRCm39)	C51Y	probably damaging	Het
Ksr2	G	T	5: 117,846,175 (GRCm39)	V681F	probably damaging	Het
Lypd2	T	C	15: 74,606,127 (GRCm39)	T4A	probably benign	Het
Man1a	A	G	10: 53,950,576 (GRCm39)	V182A	probably benign	Het
Or12j4	A	T	7: 140,046,720 (GRCm39)	D202V	probably damaging	Het
Or13e8	A	G	4: 43,696,225 (GRCm39)	F316S	possibly damaging	Het
Or2w2	A	T	13: 21,758,042 (GRCm39)	C195S	probably damaging	Het
Or51f5	A	T	7: 102,424,315 (GRCm39)	R195W	probably benign	Het
Or56b1b	T	C	7: 108,164,774 (GRCm39)	D76G	probably benign	Het
Pcdha2	C	A	18: 37,072,562 (GRCm39)	F64L	probably damaging	Het
Pgap3	G	C	11: 98,281,540 (GRCm39)	F168L	possibly damaging	Het
Pip5k1b	T	C	19: 24,416,439 (GRCm39)	N16S	probably benign	Het
Ppip5k1	T	A	2: 121,167,253 (GRCm39)	H41L	probably damaging	Het
Ppp1r9a	A	G	6: 5,159,702 (GRCm39)	R1080G	probably damaging	Het
Qrich2	A	C	11: 116,336,774 (GRCm39)		probably null	Het
Rbl2	C	T	8: 91,842,447 (GRCm39)	P1034L	probably damaging	Het
Rbpjl	GCC	GC	2: 164,256,330 (GRCm39)		probably null	Het
Rin2	A	G	2: 145,702,629 (GRCm39)	S442G	probably damaging	Het
Rtca	C	T	3: 116,293,280 (GRCm39)	R71Q	probably benign	Het
Serpind1	A	T	16: 17,157,902 (GRCm39)	N366I	probably damaging	Het
Shox2	C	G	3: 66,888,796 (GRCm39)	G32R	probably damaging	Het
Sp3	T	A	2: 72,768,466 (GRCm39)	N766Y	probably damaging	Het
Spag7	T	A	11: 70,560,059 (GRCm39)	S17C	probably null	Het
Stk25	A	T	1: 93,563,031 (GRCm39)	F7I	probably benign	Het
Tbx15	G	A	3: 99,259,880 (GRCm39)	G584S	probably benign	Het
Tenm2	T	C	11: 36,755,503 (GRCm39)	D165G	probably benign	Het
Tox2	C	A	2: 163,046,649 (GRCm39)	S42*	probably null	Het
Vmn1r39	A	G	6: 66,781,754 (GRCm39)	V188A	probably damaging	Het
Zbtb5	A	T	4: 44,993,941 (GRCm39)	M481K	probably benign	Het
Zfp26	T	C	9: 20,355,615 (GRCm39)	T56A	possibly damaging	Het
Zfp459	C	A	13: 67,556,498 (GRCm39)	C195F	probably damaging	Het
Zfp703	C	T	8: 27,469,233 (GRCm39)	P299L	probably damaging	Het
Zfp764	A	G	7: 127,004,105 (GRCm39)	I342T	probably benign	Het
Zfp942	T	C	17: 22,151,985 (GRCm39)	N7D	probably null	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
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'- TTATTCCAAAGACTCAAACAGTGCC -3'
(R):5'- TTCAGGGTTTGGGAAAGAGC -3'

Sequencing Primer
(F):5'- CAAATGCATGCATCTCTTGGTG -3'
(R):5'- AGCCTTGAAAAGCAGCATTTAG -3'

Posted On

2016-10-05