Mutagenetix > Incidental Mutation

Incidental Mutation 'R7681:Limk2'

592769

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

045747-MU

Accession Numbers

Essential gene?

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

Stock #

R7681 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

3294256-3359189 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 3303354 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 322 (S322P)

Ref Sequence

ENSEMBL: ENSMUSP00000099162 (fasta)

Gene Model

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

AlphaFold

O54785

PDB Structure

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000101638
AA Change: S322P

PolyPhen 2 Score 0.965 (Sensitivity: 0.78; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000099162
Gene: ENSMUSG00000020451
AA Change: S322P

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 benign
Transcript: ENSMUST00000101640
AA Change: S301P

PolyPhen 2 Score 0.034 (Sensitivity: 0.95; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000099163
Gene: ENSMUSG00000020451
AA Change: S301P

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 benign
Transcript: ENSMUST00000101642
AA Change: S301P

PolyPhen 2 Score 0.009 (Sensitivity: 0.96; Specificity: 0.77)

SMART Domains

Protein: ENSMUSP00000099165
Gene: ENSMUSG00000020451
AA Change: S301P

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: S135P

PolyPhen 2 Score 0.965 (Sensitivity: 0.78; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000105656
Gene: ENSMUSG00000020451
AA Change: S135P

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: 100.0%
10x: 99.8%
20x: 99.3%

Validation Efficiency

97% (58/60)

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: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb1b	C	T	5: 8,899,619 (GRCm39)	A963V	probably benign	Het
Agbl1	T	C	7: 76,094,649 (GRCm39)	V760A	unknown	Het
Akap13	T	C	7: 75,378,544 (GRCm39)	F347L	possibly damaging	Het
Anapc5	A	T	5: 122,940,202 (GRCm39)	F356L	probably benign	Het
Bmp6	A	G	13: 38,530,171 (GRCm39)	H88R	probably damaging	Het
Cblb	C	A	16: 52,025,001 (GRCm39)	S921R	probably damaging	Het
Ccs	T	A	19: 4,882,858 (GRCm39)		probably null	Het
Cyp20a1	A	G	1: 60,392,192 (GRCm39)	T83A	probably benign	Het
Defa25	T	A	8: 21,574,535 (GRCm39)	D26E	probably benign	Het
Dmwd	T	A	7: 18,815,007 (GRCm39)	N552K	probably benign	Het
Dnah17	C	T	11: 117,916,012 (GRCm39)	V4297M	probably damaging	Het
Fam135a	A	T	1: 24,106,996 (GRCm39)	S47R	probably benign	Het
Fbxo41	A	T	6: 85,455,461 (GRCm39)	C574*	probably null	Het
Fgb	T	C	3: 82,957,139 (GRCm39)		probably benign	Het
Fgfr1	C	T	8: 26,045,677 (GRCm39)	T82I	probably damaging	Het
Fhod3	T	A	18: 25,123,095 (GRCm39)	L262M	probably damaging	Het
Galnt16	A	T	12: 80,637,413 (GRCm39)	Q380L	probably damaging	Het
Glp2r	C	T	11: 67,600,505 (GRCm39)	G448D	probably benign	Het
Gnb4	C	A	3: 32,641,902 (GRCm39)	A242S	possibly damaging	Het
Golim4	T	C	3: 75,794,331 (GRCm39)		probably null	Het
Grik2	G	T	10: 49,120,476 (GRCm39)	N604K	probably damaging	Het
Hnf1b	T	G	11: 83,779,972 (GRCm39)	I435S	probably damaging	Het
Hoxa11	C	T	6: 52,222,099 (GRCm39)	G201S	probably benign	Het
Hpse	A	G	5: 100,839,257 (GRCm39)	S364P	possibly damaging	Het
Kif16b	A	T	2: 142,598,046 (GRCm39)	N525K	probably damaging	Het
Kif1a	A	T	1: 92,982,666 (GRCm39)	C704S	probably benign	Het
Lrp1b	A	T	2: 40,765,011 (GRCm39)	C2938*	probably null	Het
Malrd1	A	G	2: 16,222,913 (GRCm39)	R2071G	unknown	Het
Man2a2	T	A	7: 80,001,497 (GRCm39)	I1137F	possibly damaging	Het
Map2k6	C	T	11: 110,388,729 (GRCm39)	R224*	probably null	Het
Map3k4	G	A	17: 12,537,430 (GRCm39)	P29L	unknown	Het
Morn5	A	T	2: 35,947,156 (GRCm39)	N145Y	possibly damaging	Het
Muc20	T	C	16: 32,613,989 (GRCm39)	T463A	probably benign	Het
Myh10	C	T	11: 68,662,762 (GRCm39)	T642I	probably damaging	Het
Myh14	C	A	7: 44,273,572 (GRCm39)	R1362L	possibly damaging	Het
Nup88	C	A	11: 70,860,711 (GRCm39)	V23L	probably benign	Het
Ogfr	GGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGGGCCAGAGGACCCCCAAAGCCAGGTGG	GGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGGGCCAGAGGACCCCCAAAGCCAGGTGG	2: 180,237,059 (GRCm39)		probably benign	Het
Or13p8	A	G	4: 118,583,761 (GRCm39)	I106V	probably benign	Het
Or4c116	A	C	2: 88,941,935 (GRCm39)	V307G	probably benign	Het
Or5p56	T	C	7: 107,590,355 (GRCm39)	M261T	possibly damaging	Het
Pabpn1	T	C	14: 55,135,499 (GRCm39)	Y299H	probably damaging	Het
Pak4	T	C	7: 28,259,655 (GRCm39)	E514G	probably damaging	Het
Ppp1r12b	A	C	1: 134,793,673 (GRCm39)	S564A	probably benign	Het
Psmc2	T	C	5: 22,008,272 (GRCm39)		probably null	Het
Psme4	A	G	11: 30,741,975 (GRCm39)	Y146C	possibly damaging	Het
Rb1cc1	A	G	1: 6,310,547 (GRCm39)	D315G	probably damaging	Het
Rilpl1	A	G	5: 124,668,976 (GRCm39)	V24A	possibly damaging	Het
Rtel1	A	T	2: 180,964,187 (GRCm39)	H62L	probably damaging	Het
Ruvbl1	G	A	6: 88,444,635 (GRCm39)		probably null	Het
Scn5a	A	G	9: 119,359,043 (GRCm39)	V668A	probably benign	Het
Slc22a6	G	A	19: 8,603,493 (GRCm39)	G519E	probably benign	Het
Slc43a2	T	A	11: 75,454,499 (GRCm39)	I348N	probably benign	Het
Slc6a16	T	A	7: 44,910,338 (GRCm39)	L347Q	probably damaging	Het
Smg6	T	A	11: 74,822,531 (GRCm39)	L658H	probably damaging	Het
Spata31e4	C	T	13: 50,856,290 (GRCm39)	P643S	possibly damaging	Het
Spidr	C	A	16: 15,713,488 (GRCm39)	G832W	probably damaging	Het
Ssrp1	G	A	2: 84,876,092 (GRCm39)	G616E	probably benign	Het
Sult1b1	G	A	5: 87,678,495 (GRCm39)	L110F	probably damaging	Het
Tfec	T	A	6: 16,834,235 (GRCm39)	H224L	probably benign	Het
Ttn	C	T	2: 76,539,295 (GRCm39)	E34564K	probably benign	Het
Washc2	A	G	6: 116,237,618 (GRCm39)	D1285G	probably damaging	Het
Zfp870	T	C	17: 33,101,664 (GRCm39)	E555G	probably benign	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
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
R9617:Limk2	UTSW	11	3,297,715 (GRCm39)	missense	probably damaging	0.99

Predicted Primers

PCR Primer
(F):5'- ATCACTCACAGCCAGGAAGGAG -3'
(R):5'- CGGGATTCAAATTGTAACTGCTG -3'

Sequencing Primer
(F):5'- CTGATGACTAGAGCTGTATCCCAG -3'
(R):5'- CAAATTGTAACTGCTGGAATGACC -3'

Posted On

2019-11-12