Mutagenetix > Incidental Mutation

Incidental Mutation 'P0018:Katna1'

7719

Institutional Source

Beutler Lab

Gene Symbol

Katna1

Ensembl Gene

ENSMUSG00000019794

Gene Name

katanin p60 (ATPase-containing) subunit A1

Synonyms

MMRRC Submission

038271-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.848) question?

Stock #

P0018 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

7601764-7638914 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 7617223 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Serine at position 72 (T72S)

Ref Sequence

ENSEMBL: ENSMUSP00000133588 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000019929] [ENSMUST00000165806] [ENSMUST00000173400]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000019929
AA Change: T72S

PolyPhen 2 Score 0.201 (Sensitivity: 0.92; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000019929
Gene: ENSMUSG00000019794
AA Change: T72S

Domain	Start	End	E-Value	Type
PDB:2RPA\|A	1	72	2e-44	PDB
AAA	241	383	5.2e-22	SMART
low complexity region	387	400	N/A	INTRINSIC
Pfam:Vps4_C	438	489	3.4e-7	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000165806
AA Change: T74S

PolyPhen 2 Score 0.099 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000132514
Gene: ENSMUSG00000019794
AA Change: T74S

Domain	Start	End	E-Value	Type
PDB:2RPA\|A	1	74	6e-46	PDB
AAA	243	385	3.23e-20	SMART
low complexity region	389	402	N/A	INTRINSIC
Pfam:Vps4_C	440	491	4.8e-12	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000173400
AA Change: T72S

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000133588
Gene: ENSMUSG00000019794
AA Change: T72S

Domain	Start	End	E-Value	Type
PDB:2RPA\|A	1	72	3e-47	PDB

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000174654

Meta Mutation Damage Score

0.2020

Coding Region Coverage

1x: 83.8%
3x: 77.4%
10x: 57.9%
20x: 38.3%

Validation Efficiency

72% (76/106)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Microtubules, polymers of alpha and beta tubulin subunits, form the mitotic spindle of a dividing cell and help to organize membranous organelles during interphase. Katanin is a heterodimer that consists of a 60 kDa ATPase (p60 subunit A 1) and an 80 kDa accessory protein (p80 subunit B 1). The p60 subunit acts to sever and disassemble microtubules, while the p80 subunit targets the enzyme to the centrosome. This gene encodes the p80 subunit. This protein is a member of the AAA family of ATPases. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Feb 2011]

Allele List at MGI

All alleles(15) : Targeted(2) Gene trapped(13)

Other mutations in this stock

Total: 14 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
AAdacl4fm3	A	T	4: 144,429,767 (GRCm39)	D407E	probably benign	Het
Brip1	C	T	11: 85,999,694 (GRCm39)	V763I	possibly damaging	Het
Cspg4b	A	G	13: 113,504,040 (GRCm39)	D1723G	possibly damaging	Het
Cxxc1	C	T	18: 74,353,992 (GRCm39)	R593C	probably damaging	Het
Erbb4	T	A	1: 68,110,835 (GRCm39)	M993L	probably benign	Het
Ftsj3	C	A	11: 106,145,634 (GRCm39)	M66I	possibly damaging	Het
Galnt2	T	A	8: 125,063,350 (GRCm39)	Y357N	probably damaging	Het
Hgsnat	C	T	8: 26,458,382 (GRCm39)		probably benign	Het
Nell1	A	G	7: 49,770,439 (GRCm39)	D166G	probably damaging	Het
Nlgn1	G	T	3: 25,490,741 (GRCm39)	P329T	probably damaging	Het
Pclo	A	T	5: 14,727,735 (GRCm39)		probably benign	Het
Robo2	T	C	16: 73,843,694 (GRCm39)	I174V	possibly damaging	Het
Sufu	A	G	19: 46,463,933 (GRCm39)		probably benign	Het
Tmub1	C	A	5: 24,651,755 (GRCm39)	A55S	possibly damaging	Het

Other mutations in Katna1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00089:Katna1	APN	10	7,638,568 (GRCm39)	missense	probably damaging	1.00
IGL00332:Katna1	APN	10	7,638,758 (GRCm39)	utr 3 prime	probably benign
IGL01385:Katna1	APN	10	7,628,574 (GRCm39)	missense	probably damaging	1.00
IGL01592:Katna1	APN	10	7,617,218 (GRCm39)	missense	probably damaging	1.00
R0310:Katna1	UTSW	10	7,619,513 (GRCm39)	intron	probably benign
R2078:Katna1	UTSW	10	7,619,333 (GRCm39)	missense	probably benign	0.00
R2975:Katna1	UTSW	10	7,619,473 (GRCm39)	missense	probably benign	0.01
R3978:Katna1	UTSW	10	7,628,518 (GRCm39)	missense	probably damaging	1.00
R3979:Katna1	UTSW	10	7,628,518 (GRCm39)	missense	probably damaging	1.00
R4477:Katna1	UTSW	10	7,614,594 (GRCm39)	missense	probably damaging	0.98
R4480:Katna1	UTSW	10	7,614,594 (GRCm39)	missense	probably damaging	0.98
R5796:Katna1	UTSW	10	7,636,575 (GRCm39)	missense	probably damaging	0.98
R7938:Katna1	UTSW	10	7,637,075 (GRCm39)	missense	probably benign	0.00
R7965:Katna1	UTSW	10	7,614,623 (GRCm39)	missense	probably benign
R8275:Katna1	UTSW	10	7,628,574 (GRCm39)	missense	probably damaging	0.97
R8784:Katna1	UTSW	10	7,614,579 (GRCm39)	missense	possibly damaging	0.68
R8842:Katna1	UTSW	10	7,614,600 (GRCm39)	missense	probably benign
R9018:Katna1	UTSW	10	7,637,040 (GRCm39)	missense	probably damaging	1.00
R9784:Katna1	UTSW	10	7,638,590 (GRCm39)	missense	probably null	0.01
Z1176:Katna1	UTSW	10	7,635,549 (GRCm39)	missense	probably damaging	1.00

Protein Function and Prediction

Katna1 encodes katanin, an ATP-dependent microtubule-severing protein composed of p60 and p80 subunits that regulates cortical microtubule plus-end interactions and cell migration [(1;2); reviewed in (3)]. p60 is the catalytic subunit that oligomerizes and breaks microtubules while hydrolyzing ATP (4); p80 has been shown to assemble the central pair of microtubules in ciliary axonemes of Chlamydomonas reinhardtii [(5); reviewed in (6)].

Expression/Localization

Katna1 localizes along the length of axons at early stages of neuronal development in the rat and mouse, with expression generally higher in and near growth cones of extending axons and in distal regions. Katna1 expression declined upon neuronal maturation (7).

References

1. Zhang, D., Grode, K. D., Stewman, S. F., Diaz-Valencia, J. D., Liebling, E., Rath, U., Riera, T., Currie, J. D., Buster, D. W., Asenjo, A. B., Sosa, H. J., Ross, J. L., Ma, A., Rogers, S. L., and Sharp, D. J. (2011) Drosophila Katanin is a Microtubule Depolymerase that Regulates Cortical-Microtubule Plus-End Interactions and Cell Migration. Nat Cell Biol. 13, 361-370.

2. McNally, F. J., and Vale, R. D. (1993) Identification of Katanin, an ATPase that Severs and Disassembles Stable Microtubules. Cell. 75, 419-429.

3. Baas, P. W., and Sharma, V. (2011) Cell Migration: Katanin Gives Microtubules a Trim. Curr Biol. 21, R302-4.

4. Hartman, J. J., and Vale, R. D. (1999) Microtubule Disassembly by ATP-Dependent Oligomerization of the AAA Enzyme Katanin. Science. 286, 782-785.

5. Dymek, E. E., Lefebvre, P. A., and Smith, E. F. (2004) PF15p is the Chlamydomonas Homologue of the Katanin p80 Subunit and is Required for Assembly of Flagellar Central Microtubules. Eukaryot Cell. 3, 870-879.

6. Sharma, N., Bryant, J., Wloga, D., Donaldson, R., Davis, R. C., Jerka-Dziadosz, M., and Gaertig, J. (2007) Katanin Regulates Dynamics of Microtubules and Biogenesis of Motile Cilia. J Cell Biol. 178, 1065-1079.

7. Karabay, A., Yu, W., Solowska, J. M., Baird, D. H., and Baas, P. W. (2004) Axonal Growth is Sensitive to the Levels of Katanin, a Protein that Severs Microtubules. J Neurosci. 24, 5778-5788.

Posted On

2012-10-29

Science Writer

Anne Murray