Mutagenetix > Incidental Mutation

Incidental Mutation 'R0017:Cdca8'

8311

Institutional Source

Beutler Lab

Gene Symbol

Cdca8

Ensembl Gene

ENSMUSG00000028873

Gene Name

cell division cycle associated 8

Synonyms

D4Ertd421e, Borealin, DasraB, 4831429J16Rik

MMRRC Submission

038312-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0017 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

124812258-124830710 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 124814168 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 208 (T208A)

Ref Sequence

ENSEMBL: ENSMUSP00000081319 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000030690] [ENSMUST00000084296]

AlphaFold

Q8BHX3

Predicted Effect

probably benign
Transcript: ENSMUST00000030690
AA Change: T208A

PolyPhen 2 Score 0.150 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000030690
Gene: ENSMUSG00000028873
AA Change: T208A

Domain	Start	End	E-Value	Type
Pfam:Nbl1_Borealin_N	20	76	1.9e-20	PFAM
low complexity region	109	139	N/A	INTRINSIC
Pfam:Borealin	148	286	5.9e-27	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000084296
AA Change: T208A

PolyPhen 2 Score 0.150 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000081319
Gene: ENSMUSG00000028873
AA Change: T208A

Domain	Start	End	E-Value	Type
Pfam:Nbl1_Borealin_N	19	77	2.7e-24	PFAM
low complexity region	109	139	N/A	INTRINSIC
Pfam:Borealin	173	286	2.4e-42	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000125801

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135571

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000147074

Predicted Effect

probably benign
Transcript: ENSMUST00000149146

SMART Domains

Protein: ENSMUSP00000118801
Gene: ENSMUSG00000028876

Domain	Start	End	E-Value	Type
Pfam:Ephrin_lbd	1	66	2.2e-25	PFAM
low complexity region	74	87	N/A	INTRINSIC
FN3	193	290	6.54e-6	SMART
FN3	306	392	1.66e-7	SMART
Pfam:EphA2_TM	421	496	2.4e-15	PFAM
TyrKc	499	754	5.17e-90	SMART
SAM	784	851	1.2e-15	SMART
low complexity region	852	862	N/A	INTRINSIC

Meta Mutation Damage Score

0.4827

Coding Region Coverage

1x: 79.1%
3x: 69.1%
10x: 41.8%
20x: 21.2%

Validation Efficiency

93% (76/82)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a component of the chromosomal passenger complex. This complex is an essential regulator of mitosis and cell division. This protein is cell-cycle regulated and is required for chromatin-induced microtubule stabilization and spindle formation. Alternate splicing results in multiple transcript variants. Pseudgenes of this gene are found on chromosomes 7, 8 and 16. [provided by RefSeq, Apr 2013]
PHENOTYPE: Mice homozygous for a reporter allele exhibit early embryonic lethality due to mitotic defects associated with abnormal microtubule organization and mislocalization of the chromosomal passenger protein complex. Blastocysts fail to develop past E3.5 and undergo apoptosis by E5.5. [provided by MGI curators]

Allele List at MGI

All alleles(14) : Targeted(2) Gene trapped(12)

Other mutations in this stock

Total: 29 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700010I14Rik	G	T	17: 9,226,938 (GRCm39)		probably benign	Het
Adgrv1	T	C	13: 81,727,065 (GRCm39)	N429S	probably benign	Het
Dcdc5	G	A	2: 106,187,541 (GRCm39)		noncoding transcript	Het
Fig4	A	G	10: 41,149,003 (GRCm39)	Y150H	possibly damaging	Het
Fsip2	G	A	2: 82,822,416 (GRCm39)	V6050M	probably damaging	Het
Gpld1	A	G	13: 25,174,101 (GRCm39)	D842G	probably damaging	Het
Hmgcr	A	G	13: 96,788,597 (GRCm39)		probably benign	Het
Ifit2	A	T	19: 34,550,973 (GRCm39)	N171I	probably damaging	Het
Ipo11	T	A	13: 107,023,238 (GRCm39)	I416L	probably benign	Het
Kcnab1	G	A	3: 65,264,527 (GRCm39)	V259M	probably damaging	Het
Kif5c	A	G	2: 49,622,725 (GRCm39)	T526A	probably benign	Het
Nucb2	A	G	7: 116,132,386 (GRCm39)	D331G	probably benign	Het
Pfdn6	T	C	17: 34,158,538 (GRCm39)	R79G	probably damaging	Het
Pkd1	G	T	17: 24,797,513 (GRCm39)		probably null	Het
Ptpro	T	C	6: 137,393,825 (GRCm39)	V831A	probably benign	Het
Reg3b	T	A	6: 78,349,844 (GRCm39)	M128K	possibly damaging	Het
Rif1	A	G	2: 52,006,686 (GRCm39)	T2207A	probably benign	Het
Rpa1	A	C	11: 75,205,687 (GRCm39)	N223K	probably null	Het
Rras2	T	C	7: 113,647,490 (GRCm39)		probably benign	Het
Scyl3	T	A	1: 163,767,538 (GRCm39)	I204N	possibly damaging	Het
Slc45a1	C	A	4: 150,714,023 (GRCm39)	D741Y	possibly damaging	Het
Slco1a5	A	T	6: 142,182,061 (GRCm39)		probably benign	Het
Smg5	G	T	3: 88,258,412 (GRCm39)	R461L	probably damaging	Het
Sync	G	A	4: 129,187,537 (GRCm39)	V190M	probably damaging	Het
Tshr	A	T	12: 91,504,660 (GRCm39)	I533F	possibly damaging	Het
Tsn	T	C	1: 118,228,589 (GRCm39)	D211G	probably damaging	Het
Ttn	G	A	2: 76,621,988 (GRCm39)	T15518I	probably benign	Het
Vapb	A	G	2: 173,613,397 (GRCm39)	T99A	probably benign	Het
Zfp280d	A	T	9: 72,246,292 (GRCm39)		probably null	Het

Other mutations in Cdca8

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
P0024:Cdca8	UTSW	4	124,820,457 (GRCm39)	critical splice donor site	probably null
R0017:Cdca8	UTSW	4	124,814,168 (GRCm39)	missense	probably benign	0.15
R0025:Cdca8	UTSW	4	124,815,047 (GRCm39)	missense	possibly damaging	0.90
R1024:Cdca8	UTSW	4	124,815,798 (GRCm39)	missense	probably benign	0.00
R4689:Cdca8	UTSW	4	124,824,896 (GRCm39)	missense	probably damaging	1.00
R5077:Cdca8	UTSW	4	124,820,470 (GRCm39)	missense	probably damaging	1.00
R5597:Cdca8	UTSW	4	124,812,793 (GRCm39)	missense	probably damaging	1.00
R6319:Cdca8	UTSW	4	124,815,087 (GRCm39)	missense	possibly damaging	0.81
R6390:Cdca8	UTSW	4	124,830,168 (GRCm39)	missense	probably damaging	1.00
R7818:Cdca8	UTSW	4	124,820,456 (GRCm39)	critical splice donor site	probably null
R9100:Cdca8	UTSW	4	124,830,238 (GRCm39)	missense	probably benign	0.25
R9605:Cdca8	UTSW	4	124,830,384 (GRCm39)	missense	probably damaging	1.00
R9765:Cdca8	UTSW	4	124,814,122 (GRCm39)	missense	probably benign	0.11
X0026:Cdca8	UTSW	4	124,820,496 (GRCm39)	missense	probably damaging	1.00

Protein Function and Prediction

Cdca8 encodes Borealin (alternatively, Dasra B), a non-enzymatic member of the chromosomal passenger complex that is involved in regulatory roles at the centromeres and central spindle in mitosis (1). Chromosomal passenger activity is required for phosphorylation of histone H3, correction of kinetochore attachment errors, aspects of the spindle assembly checkpoint, assembly of a stable bipolar spindle, and the completion of cytokinesis [reviewed in (2)]. RNAi of Borealin results in mitotic delay as well as kinetochore-spindle misattachments an increase in bipolar spindles associated with ectopic asters (1). Borealin, along with Survivin, mediate centromere docking [reviewed in (3)].

Expression/Localization

Similar to other chromosomal passenger proteins, Borealin is nuclear in G2, associates with condensing chromosomes in prophase, accumulate at the inner centromeres in prometaphase and metaphase then, at anaphase onset, leave the chromosomes and transfer to the central spindle to finally concentrate in the midbody at cytokinesis [(4); reviewed in (2)].

Background

Cdca8^{tm1Tatn/tm1Tatn}; MGI:3795253

involves: C57BL/6 * CBA

Mice homozygous for a reporter allele exhibit early embryonic lethality due to mitotic defects associated with abnormal microtubule organization and mislocalization of the chromosomal passenger protein complex (5). Blastocysts fail to develop past E3.5 and undergo apoptosis by E5.5 (5).

References

1. Gassmann, R., Carvalho, A., Henzing, A. J., Ruchaud, S., Hudson, D. F., Honda, R., Nigg, E. A., Gerloff, D. L., and Earnshaw, W. C. (2004) Borealin: A Novel Chromosomal Passenger Required for Stability of the Bipolar Mitotic Spindle. J Cell Biol. 166, 179-191.

2. Vagnarelli, P., and Earnshaw, W. C. (2004) Chromosomal Passengers: The Four-Dimensional Regulation of Mitotic Events. Chromosoma. 113, 211-222.

3. van der Waal, M. S., Hengeveld, R. C., van der Horst, A., and Lens, S. M. (2012) Cell Division Control by the Chromosomal Passenger Complex. Exp Cell Res. 318, 1407-1420.

4. Cooke, C. A., Heck, M. M., and Earnshaw, W. C. (1987) The Inner Centromere Protein (INCENP) Antigens: Movement from Inner Centromere to Midbody during Mitosis. J Cell Biol. 105, 2053-2067.

5. Yamanaka, Y., Heike, T., Kumada, T., Shibata, M., Takaoka, Y., Kitano, A., Shiraishi, K., Kato, T., Nagato, M., Okawa, K., Furushima, K., Nakao, K., Nakamura, Y., Taketo, M. M., Aizawa, S., and Nakahata, T. (2008) Loss of Borealin/DasraB Leads to Defective Cell Proliferation, p53 Accumulation and Early Embryonic Lethality. Mech Dev. 125, 441-450.

Posted On

2012-11-21

Science Writer

Anne Murray