Mutagenetix > Incidental Mutation

Incidental Mutation 'R9617:Limk2'

726527

Institutional Source

Beutler Lab

Gene Symbol

Limk2

Ensembl Gene

ENSMUSG00000020451

Gene Name

LIM domain kinase 2

Synonyms

whe, Limk2b, Limk2a, A930024P04Rik, LIM kinase 2

MMRRC Submission

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.186) question?

Stock #

R9617 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

3294256-3359189 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 3297715 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 473 (S473P)

Ref Sequence

ENSEMBL: ENSMUSP00000099162 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000045153] [ENSMUST00000101638] [ENSMUST00000101640] [ENSMUST00000101642] [ENSMUST00000110029]

AlphaFold

O54785

PDB Structure

Solution structure of the PDZ domain from mouse LIM domain kinase [SOLUTION NMR]

Predicted Effect

probably benign
Transcript: ENSMUST00000045153

SMART Domains

Protein: ENSMUSP00000036921
Gene: ENSMUSG00000034614

Domain	Start	End	E-Value	Type
signal peptide	1	21	N/A	INTRINSIC
KR	23	103	3.64e-17	SMART
transmembrane domain	170	192	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000101638
AA Change: S473P

PolyPhen 2 Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000099162
Gene: ENSMUSG00000020451
AA Change: S473P

Domain	Start	End	E-Value	Type
LIM	11	63	2e-14	SMART
LIM	71	124	4.63e-10	SMART
PDZ	161	239	7.04e-10	SMART
low complexity region	241	255	N/A	INTRINSIC
low complexity region	280	306	N/A	INTRINSIC
low complexity region	310	322	N/A	INTRINSIC
Pfam:Pkinase	331	600	5.3e-48	PFAM
Pfam:Pkinase_Tyr	331	601	4.7e-50	PFAM
Pfam:Kdo	341	497	8.6e-7	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000101640
AA Change: S458P

PolyPhen 2 Score 0.971 (Sensitivity: 0.77; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000099163
Gene: ENSMUSG00000020451
AA Change: S458P

Domain	Start	End	E-Value	Type
LIM	7	42	4.91e-1	SMART
LIM	50	103	4.63e-10	SMART
PDZ	140	218	7.04e-10	SMART
low complexity region	220	234	N/A	INTRINSIC
low complexity region	259	285	N/A	INTRINSIC
low complexity region	289	301	N/A	INTRINSIC
Pfam:Pkinase	310	582	1.2e-45	PFAM
Pfam:Pkinase_Tyr	310	586	1.3e-51	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000101642
AA Change: S452P

PolyPhen 2 Score 0.964 (Sensitivity: 0.78; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000099165
Gene: ENSMUSG00000020451
AA Change: S452P

Domain	Start	End	E-Value	Type
LIM	7	42	4.91e-1	SMART
LIM	50	103	4.63e-10	SMART
PDZ	140	218	7.04e-10	SMART
low complexity region	220	234	N/A	INTRINSIC
low complexity region	259	285	N/A	INTRINSIC
low complexity region	289	301	N/A	INTRINSIC
Pfam:Pkinase	310	579	4.9e-48	PFAM
Pfam:Pkinase_Tyr	310	580	4.3e-50	PFAM
Pfam:Kdo	320	476	8.2e-7	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000110029
AA Change: S286P

PolyPhen 2 Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000105656
Gene: ENSMUSG00000020451
AA Change: S286P

Domain	Start	End	E-Value	Type
PDZ	1	52	4.55e-1	SMART
low complexity region	54	68	N/A	INTRINSIC
low complexity region	93	119	N/A	INTRINSIC
low complexity region	123	135	N/A	INTRINSIC
Pfam:Pkinase	144	411	2.7e-49	PFAM
Pfam:Pkinase_Tyr	144	414	1.7e-51	PFAM

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.1%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] There are approximately 40 known eukaryotic LIM proteins, so named for the LIM domains they contain. LIM domains are highly conserved cysteine-rich structures containing 2 zinc fingers. Although zinc fingers usually function by binding to DNA or RNA, the LIM motif probably mediates protein-protein interactions. LIM kinase-1 and LIM kinase-2 belong to a small subfamily with a unique combination of 2 N-terminal LIM motifs and a C-terminal protein kinase domain. The protein encoded by this gene is phosphorylated and activated by ROCK, a downstream effector of Rho, and the encoded protein, in turn, phosphorylates cofilin, inhibiting its actin-depolymerizing activity. It is thought that this pathway contributes to Rho-induced reorganization of the actin cytoskeleton. At least three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
PHENOTYPE: Male homozygotes for targeted null mutations exhibit small testes but are fertile. Mutant kidneys have fewer glomeruli and dilated renal tubules, but function normally. Mice homozygous for a gene trap allele or spontaneous mutation have open eyelids at birth, corneal abnormalities and inflammation. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 75 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1110032F04Rik	C	T	3: 68,777,402 (GRCm39)	P121L	probably damaging	Het
4930442H23Rik	C	T	10: 81,018,976 (GRCm39)	V16I	unknown	Het
4930444P10Rik	T	C	1: 16,139,051 (GRCm39)	M97V	probably benign	Het
Abcb1a	A	T	5: 8,797,353 (GRCm39)		probably null	Het
Abhd5	T	C	9: 122,197,035 (GRCm39)	I74T	probably benign	Het
Ankle2	T	A	5: 110,399,409 (GRCm39)	F590I	probably damaging	Het
C2cd6	T	C	1: 59,097,848 (GRCm39)	S414G	probably benign	Het
Catsperd	G	A	17: 56,968,252 (GRCm39)	D546N	probably benign	Het
Cep295nl	G	T	11: 118,224,000 (GRCm39)	H281Q	possibly damaging	Het
Cfap69	T	C	5: 5,639,164 (GRCm39)	E670G	probably damaging	Het
Cfh	A	T	1: 140,090,718 (GRCm39)	V90E	possibly damaging	Het
Cnksr3	A	C	10: 7,079,021 (GRCm39)		probably null	Het
Cntrl	T	A	2: 35,035,077 (GRCm39)	F901L	probably benign	Het
Coch	T	A	12: 51,645,034 (GRCm39)	M196K	probably damaging	Het
Crygd	T	C	1: 65,102,369 (GRCm39)	N34S	probably damaging	Het
Ctdp1	A	T	18: 80,492,962 (GRCm39)	I511N	probably benign	Het
Dhx30	C	T	9: 109,926,186 (GRCm39)	A142T	probably damaging	Het
Dlg2	T	C	7: 92,087,284 (GRCm39)		probably null	Het
Dmxl1	A	G	18: 49,998,228 (GRCm39)	D776G	probably damaging	Het
Dnm3	C	T	1: 162,149,354 (GRCm39)	G197D	probably damaging	Het
Eif4g3	A	G	4: 137,824,190 (GRCm39)	H91R	probably damaging	Het
Ephb6	A	G	6: 41,596,258 (GRCm39)	M844V	probably damaging	Het
Erc1	T	C	6: 119,773,902 (GRCm39)	E351G	probably benign	Het
Etfbkmt	G	A	6: 149,045,744 (GRCm39)	G33R	probably benign	Het
Fnbp4	T	C	2: 90,588,738 (GRCm39)	I503T	probably benign	Het
Gm6370	A	T	5: 146,429,993 (GRCm39)	Q143L	probably benign	Het
Gnas	T	C	2: 174,141,988 (GRCm39)	V719A	possibly damaging	Het
H13	C	A	2: 152,530,873 (GRCm39)	D219E	probably damaging	Het
Hhatl	G	A	9: 121,618,191 (GRCm39)	T188I	possibly damaging	Het
Ifi27l2b	C	T	12: 103,422,683 (GRCm39)	A45T	probably damaging	Het
Kbtbd8	T	C	6: 95,103,874 (GRCm39)	C585R	possibly damaging	Het
Lrba	G	A	3: 86,267,169 (GRCm39)	G1620S	probably benign	Het
Lrrtm2	T	C	18: 35,346,490 (GRCm39)	T271A	probably benign	Het
Map3k4	A	G	17: 12,476,871 (GRCm39)	S759P	possibly damaging	Het
Mybphl	G	T	3: 108,282,952 (GRCm39)	V247F	possibly damaging	Het
Myh10	T	A	11: 68,682,815 (GRCm39)	V1120D	probably benign	Het
Naip1	T	C	13: 100,569,821 (GRCm39)	N271S	probably benign	Het
Napepld	C	T	5: 21,875,561 (GRCm39)	V328I	probably damaging	Het
Nucb1	A	G	7: 45,148,159 (GRCm39)	V218A	probably benign	Het
Nup107	A	T	10: 117,593,238 (GRCm39)	D813E	probably benign	Het
Or14j3	T	A	17: 37,901,053 (GRCm39)	K64*	probably null	Het
Or5g29	T	A	2: 85,421,279 (GRCm39)	Y132N	probably damaging	Het
Or6c35	A	T	10: 129,168,794 (GRCm39)	T15S	probably damaging	Het
Or8g52	A	G	9: 39,630,678 (GRCm39)	S52G	possibly damaging	Het
Pabpc2	T	C	18: 39,907,602 (GRCm39)	I289T	probably benign	Het
Parg	A	G	14: 31,960,569 (GRCm39)	I600V	probably benign	Het
Patj	T	C	4: 98,393,991 (GRCm39)	F975L	probably benign	Het
Pcdhb17	A	G	18: 37,618,218 (GRCm39)	T3A	probably benign	Het
Piezo2	T	C	18: 63,248,108 (GRCm39)	E464G	probably benign	Het
Pkd1	T	A	17: 24,800,341 (GRCm39)	V3034D	probably damaging	Het
Pld2	A	G	11: 70,447,944 (GRCm39)	E869G	probably damaging	Het
Plek	T	A	11: 16,945,311 (GRCm39)	L29F	possibly damaging	Het
Prelp	A	G	1: 133,842,416 (GRCm39)	L243P	probably damaging	Het
Rapgef5	T	A	12: 117,621,930 (GRCm39)	D231E	probably benign	Het
Riok1	A	G	13: 38,244,016 (GRCm39)	E514G	probably benign	Het
Rmdn2	T	C	17: 79,928,790 (GRCm39)	M14T	probably benign	Het
Rorb	G	A	19: 18,939,499 (GRCm39)	Q228*	probably null	Het
Scmh1	T	A	4: 120,340,827 (GRCm39)	M171K	probably damaging	Het
Scn9a	A	G	2: 66,392,809 (GRCm39)	L261P	probably damaging	Het
Senp7	A	T	16: 55,971,652 (GRCm39)	N263I	probably benign	Het
Slc11a1	G	T	1: 74,419,041 (GRCm39)	A162S	probably benign	Het
Slc6a17	A	G	3: 107,384,685 (GRCm39)	V305A	probably damaging	Het
Snph	A	T	2: 151,435,422 (GRCm39)	V502E	probably damaging	Het
Sost	G	T	11: 101,854,892 (GRCm39)	A139E	possibly damaging	Het
Srp54a	A	T	12: 55,136,061 (GRCm39)	E25D	probably benign	Het
Tmeff1	T	A	4: 48,636,940 (GRCm39)	C213S	probably damaging	Het
Tmem232	A	T	17: 65,807,180 (GRCm39)	Y4*	probably null	Het
Tmem63c	T	G	12: 87,103,361 (GRCm39)	I45S	probably benign	Het
Ttbk1	C	T	17: 46,757,998 (GRCm39)	G879S	probably damaging	Het
Ugt1a7c	A	G	1: 88,022,952 (GRCm39)	H37R	probably damaging	Het
Vmn1r236	T	C	17: 21,507,053 (GRCm39)	L57P	probably damaging	Het
Wnk2	T	A	13: 49,192,453 (GRCm39)	E675V	unknown	Het
Wnt10b	T	C	15: 98,674,609 (GRCm39)	T43A	probably damaging	Het
Wnt8a	C	A	18: 34,680,163 (GRCm39)	T176K	probably benign	Het
Zfp937	T	A	2: 150,080,452 (GRCm39)	C161S	probably damaging	Het

Other mutations in Limk2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01105:Limk2	APN	11	3,305,475 (GRCm39)	splice site	probably benign
IGL01592:Limk2	APN	11	3,309,052 (GRCm39)	missense	probably benign	0.00
IGL01716:Limk2	APN	11	3,308,990 (GRCm39)	splice site	probably null
IGL01911:Limk2	APN	11	3,305,340 (GRCm39)	missense	probably benign
R0900:Limk2	UTSW	11	3,300,731 (GRCm39)	missense	probably damaging	1.00
R1587:Limk2	UTSW	11	3,303,455 (GRCm39)	missense	possibly damaging	0.82
R1632:Limk2	UTSW	11	3,296,250 (GRCm39)	missense	probably damaging	1.00
R1695:Limk2	UTSW	11	3,303,275 (GRCm39)	critical splice donor site	probably null
R1712:Limk2	UTSW	11	3,308,104 (GRCm39)	splice site	probably null
R1792:Limk2	UTSW	11	3,308,236 (GRCm39)	missense	probably benign
R1982:Limk2	UTSW	11	3,305,461 (GRCm39)	missense	probably benign	0.00
R3009:Limk2	UTSW	11	3,309,046 (GRCm39)	missense	probably benign	0.01
R4565:Limk2	UTSW	11	3,298,634 (GRCm39)	missense	probably damaging	0.98
R4703:Limk2	UTSW	11	3,297,586 (GRCm39)	nonsense	probably null
R4978:Limk2	UTSW	11	3,359,069 (GRCm39)	utr 5 prime	probably benign
R5160:Limk2	UTSW	11	3,300,772 (GRCm39)	missense	probably damaging	1.00
R5460:Limk2	UTSW	11	3,302,332 (GRCm39)	missense	probably benign	0.30
R6497:Limk2	UTSW	11	3,310,492 (GRCm39)	missense	probably benign	0.00
R6543:Limk2	UTSW	11	3,300,682 (GRCm39)	missense	probably damaging	1.00
R6666:Limk2	UTSW	11	3,310,493 (GRCm39)	missense	probably damaging	1.00
R7054:Limk2	UTSW	11	3,305,448 (GRCm39)	missense	possibly damaging	0.95
R7330:Limk2	UTSW	11	3,296,311 (GRCm39)	missense	probably benign	0.39
R7681:Limk2	UTSW	11	3,303,354 (GRCm39)	missense	probably damaging	0.96
R7722:Limk2	UTSW	11	3,306,092 (GRCm39)	splice site	probably null
R7745:Limk2	UTSW	11	3,305,896 (GRCm39)	missense	probably damaging	0.99
R8120:Limk2	UTSW	11	3,298,589 (GRCm39)	splice site	probably null
R8193:Limk2	UTSW	11	3,297,691 (GRCm39)	missense	possibly damaging	0.79
R8379:Limk2	UTSW	11	3,321,162 (GRCm39)	start gained	probably benign
R8557:Limk2	UTSW	11	3,296,379 (GRCm39)	missense	possibly damaging	0.89
R8708:Limk2	UTSW	11	3,300,763 (GRCm39)	missense	probably benign	0.19

Predicted Primers

PCR Primer
(F):5'- AAGACATGGCTTCTGTCTTCC -3'
(R):5'- TGTGGGCAGATACCAGACTG -3'

Sequencing Primer
(F):5'- GACATGGCTTCTGTCTTCCCTCTG -3'
(R):5'- CCCAGGGACAGGTTAGAG -3'

Posted On

2022-10-06