Mutagenetix > Incidental Mutation

Incidental Mutation 'P0016:Kif27'

7591

Institutional Source

Beutler Lab

Gene Symbol

Kif27

Ensembl Gene

ENSMUSG00000060176

Gene Name

kinesin family member 27

Synonyms

4930517I18Rik

MMRRC Submission

038269-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.159) question?

Stock #

P0016 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

58435316-58506936 bp(-) (GRCm39)

Type of Mutation

nonsense

DNA Base Change (assembly)

G to A at 58451266 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Stop codon at position 1021 (Q1021*)

Ref Sequence

ENSEMBL: ENSMUSP00000153598 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000043605] [ENSMUST00000224694] [ENSMUST00000225388]

AlphaFold

Q7M6Z4

Predicted Effect

probably null
Transcript: ENSMUST00000043605
AA Change: Q1021*

SMART Domains

Protein: ENSMUSP00000043304
Gene: ENSMUSG00000060176
AA Change: Q1021*

Domain	Start	End	E-Value	Type
KISc	3	349	9.18e-160	SMART
low complexity region	369	385	N/A	INTRINSIC
coiled coil region	386	418	N/A	INTRINSIC
Blast:KISc	486	566	5e-29	BLAST
coiled coil region	710	790	N/A	INTRINSIC
coiled coil region	835	891	N/A	INTRINSIC
coiled coil region	916	972	N/A	INTRINSIC
low complexity region	993	1008	N/A	INTRINSIC
coiled coil region	1010	1078	N/A	INTRINSIC
coiled coil region	1186	1226	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000180882

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000190479

Predicted Effect

probably benign
Transcript: ENSMUST00000224694

Predicted Effect

probably null
Transcript: ENSMUST00000225388
AA Change: Q1021*

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000225680

Meta Mutation Damage Score

0.9755

Coding Region Coverage

1x: 85.6%
3x: 81.0%
10x: 66.8%
20x: 50.1%

Validation Efficiency

96% (97/101)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the KIF27 (kinesin 4) sub-family of the mammalian kinesin family. The gene is an ortholog of the Drosophila Cos2 gene, which plays an important role in the Hedgehog signaling pathway. The encoded protein contains an N-terminal motor domain which includes nucleotide-binding and microtubule-interacting regions, a stalk domain containing a predicted coiled coil motif and a C-terminal tail domain. Alternatively spliced transcript variants have been observed for this gene. Pseudogenes associated with this gene are located on chromosome 9. [provided by RefSeq, Dec 2012]
PHENOTYPE: Homozygous mice are small and die by 8 weeks and exhibit hydrocephalus, rhinitis and otitis media. [provided by MGI curators]

Allele List at MGI

All alleles(9) : Targeted(2) Gene trapped(7)

Other mutations in this stock

Total: 18 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700123K08Rik	A	T	5: 138,561,200 (GRCm39)	L154*	probably null	Het
4930432E11Rik	T	C	7: 29,262,537 (GRCm39)		noncoding transcript	Het
Arap3	T	A	18: 38,117,401 (GRCm39)	T892S	probably benign	Het
Ctnnd2	G	A	15: 30,967,084 (GRCm39)	V987I	probably benign	Het
Dennd6b	T	C	15: 89,071,180 (GRCm39)	I351V	probably benign	Het
Klb	G	A	5: 65,537,266 (GRCm39)	W865*	probably null	Het
Mbd1	C	T	18: 74,407,609 (GRCm39)	R130*	probably null	Het
Mroh7	T	A	4: 106,565,054 (GRCm39)		probably null	Het
Myo16	C	T	8: 10,450,596 (GRCm39)		probably benign	Het
Rbm22	T	A	18: 60,703,842 (GRCm39)		probably benign	Het
Rnaseh2a	C	G	8: 85,686,429 (GRCm39)	D206H	probably damaging	Het
Slain1	A	G	14: 103,923,110 (GRCm39)	T187A	probably benign	Het
Slamf6	A	G	1: 171,764,068 (GRCm39)	T154A	probably damaging	Het
Traip	A	G	9: 107,845,855 (GRCm39)	D316G	possibly damaging	Het
Ttn	T	C	2: 76,641,527 (GRCm39)	D5196G	probably damaging	Het
Ubr5	C	T	15: 38,000,822 (GRCm39)	V1569M	probably damaging	Het
Zfp750	T	A	11: 121,404,804 (GRCm39)	K24*	probably null	Het
Zfp799	T	C	17: 33,038,331 (GRCm39)	E645G	possibly damaging	Het

Other mutations in Kif27

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00264:Kif27	APN	13	58,485,418 (GRCm39)	missense	probably benign
IGL00421:Kif27	APN	13	58,491,703 (GRCm39)	missense	probably damaging	1.00
IGL00903:Kif27	APN	13	58,492,486 (GRCm39)	missense	possibly damaging	0.69
IGL01024:Kif27	APN	13	58,436,015 (GRCm39)	missense	possibly damaging	0.71
IGL01070:Kif27	APN	13	58,491,907 (GRCm39)	missense	probably damaging	1.00
IGL01761:Kif27	APN	13	58,485,459 (GRCm39)	missense	probably benign
IGL02160:Kif27	APN	13	58,473,812 (GRCm39)	missense	probably damaging	1.00
IGL03162:Kif27	APN	13	58,459,021 (GRCm39)	missense	probably benign	0.03
R0016:Kif27	UTSW	13	58,502,528 (GRCm39)	missense	probably damaging	1.00
R0016:Kif27	UTSW	13	58,502,528 (GRCm39)	missense	probably damaging	1.00
R0018:Kif27	UTSW	13	58,435,867 (GRCm39)	missense	probably benign
R0018:Kif27	UTSW	13	58,435,867 (GRCm39)	missense	probably benign
R0049:Kif27	UTSW	13	58,451,378 (GRCm39)	missense	probably damaging	1.00
R0049:Kif27	UTSW	13	58,451,378 (GRCm39)	missense	probably damaging	1.00
R0481:Kif27	UTSW	13	58,459,078 (GRCm39)	splice site	probably benign
R0960:Kif27	UTSW	13	58,471,781 (GRCm39)	missense	probably damaging	0.99
R1015:Kif27	UTSW	13	58,468,029 (GRCm39)	missense	probably damaging	1.00
R1205:Kif27	UTSW	13	58,492,019 (GRCm39)	missense	probably benign	0.00
R1478:Kif27	UTSW	13	58,451,359 (GRCm39)	missense	probably damaging	0.98
R1789:Kif27	UTSW	13	58,491,822 (GRCm39)	missense	probably damaging	1.00
R1959:Kif27	UTSW	13	58,440,937 (GRCm39)	missense	probably benign	0.00
R1961:Kif27	UTSW	13	58,440,937 (GRCm39)	missense	probably benign	0.00
R3508:Kif27	UTSW	13	58,461,026 (GRCm39)	missense	possibly damaging	0.88
R4168:Kif27	UTSW	13	58,493,562 (GRCm39)	missense	probably benign	0.01
R4247:Kif27	UTSW	13	58,435,731 (GRCm39)	missense	probably damaging	0.98
R4307:Kif27	UTSW	13	58,491,937 (GRCm39)	missense	probably benign	0.00
R4621:Kif27	UTSW	13	58,478,827 (GRCm39)	missense	probably benign	0.13
R4660:Kif27	UTSW	13	58,471,730 (GRCm39)	missense	probably damaging	0.99
R4661:Kif27	UTSW	13	58,471,730 (GRCm39)	missense	probably damaging	0.99
R4736:Kif27	UTSW	13	58,476,785 (GRCm39)	missense	probably benign	0.04
R4770:Kif27	UTSW	13	58,492,191 (GRCm39)	missense	probably damaging	1.00
R4853:Kif27	UTSW	13	58,459,072 (GRCm39)	missense	probably benign	0.06
R4963:Kif27	UTSW	13	58,476,808 (GRCm39)	missense	possibly damaging	0.85
R4998:Kif27	UTSW	13	58,440,957 (GRCm39)	missense	probably damaging	0.98
R5134:Kif27	UTSW	13	58,438,904 (GRCm39)	missense	possibly damaging	0.80
R5225:Kif27	UTSW	13	58,440,915 (GRCm39)	missense	possibly damaging	0.88
R5835:Kif27	UTSW	13	58,460,960 (GRCm39)	critical splice donor site	probably null
R5875:Kif27	UTSW	13	58,458,918 (GRCm39)	missense	probably benign	0.01
R5929:Kif27	UTSW	13	58,491,784 (GRCm39)	missense	probably benign	0.01
R6175:Kif27	UTSW	13	58,459,051 (GRCm39)	missense	probably damaging	1.00
R6446:Kif27	UTSW	13	58,493,530 (GRCm39)	missense	probably damaging	1.00
R6628:Kif27	UTSW	13	58,502,611 (GRCm39)	missense	probably damaging	1.00
R7480:Kif27	UTSW	13	58,436,025 (GRCm39)	missense	probably benign	0.34
R8381:Kif27	UTSW	13	58,438,991 (GRCm39)	missense	probably benign	0.00
R8815:Kif27	UTSW	13	58,476,818 (GRCm39)	missense	probably damaging	0.97
R8993:Kif27	UTSW	13	58,473,912 (GRCm39)	missense	possibly damaging	0.93
R9181:Kif27	UTSW	13	58,492,543 (GRCm39)	missense	probably damaging	1.00
R9486:Kif27	UTSW	13	58,492,348 (GRCm39)	missense	probably damaging	1.00
Z1088:Kif27	UTSW	13	58,435,847 (GRCm39)	missense	probably benign

Protein Function and Prediction

Kif27 is a member of the kinesin superfamily (the kinesin-4 family (1)) of motor proteins that function in diverse cellular processes such as neuronal transport and mitosis/cytokinesis (2;3). Kif27 is a paralogue of Kif7, another member of the kinesin family (4); both are putative ciliary motors on primary cilia (5). Kif27 is an orthologue of the Drosophila melanogaster kinesin-like protein called Costal-2 (Cos2) that is essential for Hedgehog signaling during embryogenesis and tumorigenesis (6;7).

Expression/Localization

EST database analysis showed KIF27 mRNA expression in testis, pancreatic islet, germ cell tumors, and Jurkat T cells (4).

Background

Kif27^{Gt(OST441915)Lex/Gt(OST441915)Lex}; MGI:4318693

involves: 129S5/SvEvBrd * C57BL/6J

Homozygous animals exhibit intraventricular hemorrhage, decreased body size, increased susceptibility to otitis media, hydrocephalus, and impaired mucociliary clearance; ciliary defects were not detected (8).

Mutations in the KIF27 paralogue, KIF7, are associated with acrocallosal syndrome (OMIM #200990), hydrolethalus syndrome 2 (OMIM #614120), and Joubert syndrome 12 (OMIM #200990). Acrocallosal syndrome is an autosomal recessive mental retardation syndrome with brain abnormalities such as corpus callosum agenesis and/or Dandy-Walker malformation as well as dysmorphic features, postaxial polydactyly of the hands, and preaxial polydactyly of the feet. Hydrolethalus syndrome is an autosomal recessive embryonic lethal disorder characterized by hydrocephaly or anencephaly, postaxial polydactyly of the upper limbs, and pre- or postaxial polydactyly of the lower limbs. Joubert syndrome is a clinically and genetically heterogeneous group of disorders characterized by hypoplasia of the cerebellar vermis with the characteristic neuroradiologic 'molar tooth sign,' and accompanying neurologic symptoms, including dysregulation of breathing pattern and developmental delay.

References

1. Katoh, Y., and Katoh, M. (2004) KIF27 is One of Orthologs for Drosophila Costal-2. Int J Oncol. 25, 1875-1880.

2. Klejnot, M., and Kozielski, F. (2012) Structural Insights into Human Kif7, a Kinesin Involved in Hedgehog Signalling. Acta Crystallogr D Biol Crystallogr. 68, 154-159.

3. Hirokawa, N., Noda, Y., Tanaka, Y., and Niwa, S. (2009) Kinesin Superfamily Motor Proteins and Intracellular Transport. Nat Rev Mol Cell Biol. 10, 682-696.

4. Katoh, Y., and Katoh, M. (2004) Characterization of KIF7 Gene in Silico. Int J Oncol. 25, 1881-1886.

5. Verhey, K. J., Dishinger, J., and Kee, H. L. (2011) Kinesin Motors and Primary Cilia. Biochem Soc Trans. 39, 1120-1125.

6. Thayer, S. P., di Magliano, M. P., Heiser, P. W., Nielsen, C. M., Roberts, D. J., Lauwers, G. Y., Qi, Y. P., Gysin, S., Fernandez-del Castillo, C., Yajnik, V., Antoniu, B., McMahon, M., Warshaw, A. L., and Hebrok, M. (2003) Hedgehog is an Early and Late Mediator of Pancreatic Cancer Tumorigenesis. Nature. 425, 851-856.

7. Bijlsma, M. F., Spek, C. A., and Peppelenbosch, M. P. (2004) Hedgehog: An Unusual Signal Transducer. Bioessays. 26, 387-394.

8. Vogel, P., Read, R. W., Hansen, G. M., Payne, B. J., Small, D., Sands, A. T., and Zambrowicz, B. P. (2012) Congenital Hydrocephalus in Genetically Engineered Mice. Vet Pathol. 49, 166-181.

Posted On

2012-10-05

Science Writer

Anne Murray