Mutagenetix > Incidental Mutation

Incidental Mutation 'R2063:Slc12a5'

228819

Institutional Source

Beutler Lab

Gene Symbol

Slc12a5

Ensembl Gene

ENSMUSG00000017740

Gene Name

solute carrier family 12, member 5

Synonyms

KCC2

MMRRC Submission

040068-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R2063 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

164960802-164999731 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 164997147 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Tryptophan at position 1072 (R1072W)

Ref Sequence

ENSEMBL: ENSMUSP00000143870 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000040381] [ENSMUST00000099092] [ENSMUST00000121377] [ENSMUST00000122070] [ENSMUST00000202223] [ENSMUST00000202479] [ENSMUST00000202623]

AlphaFold

Q91V14

Predicted Effect

probably benign
Transcript: ENSMUST00000040381

SMART Domains

Protein: ENSMUSP00000046388
Gene: ENSMUSG00000039804

Domain	Start	End	E-Value	Type
low complexity region	46	79	N/A	INTRINSIC
low complexity region	82	104	N/A	INTRINSIC
low complexity region	107	118	N/A	INTRINSIC
coiled coil region	163	190	N/A	INTRINSIC
SCOP:d1kmma1	195	287	2e-9	SMART
PDB:1V95\|A	197	314	3e-79	PDB
low complexity region	324	340	N/A	INTRINSIC
low complexity region	367	376	N/A	INTRINSIC
low complexity region	395	427	N/A	INTRINSIC
low complexity region	440	460	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000099092
AA Change: R1054W

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000096690
Gene: ENSMUSG00000017740
AA Change: R1054W

Domain	Start	End	E-Value	Type
low complexity region	10	22	N/A	INTRINSIC
low complexity region	77	90	N/A	INTRINSIC
Pfam:AA_permease	102	304	5.2e-22	PFAM
Pfam:AA_permease_2	364	632	1e-17	PFAM
Pfam:AA_permease	389	676	1.9e-42	PFAM
Pfam:SLC12	688	814	2.1e-19	PFAM
Pfam:SLC12	807	959	1.8e-20	PFAM
low complexity region	978	1002	N/A	INTRINSIC
Pfam:SLC12	1009	1115	2.1e-15	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000121377

SMART Domains

Protein: ENSMUSP00000113872
Gene: ENSMUSG00000039804

Domain	Start	End	E-Value	Type
PDB:1V95\|A	1	34	2e-15	PDB
low complexity region	44	60	N/A	INTRINSIC
low complexity region	87	96	N/A	INTRINSIC
low complexity region	115	147	N/A	INTRINSIC
low complexity region	160	180	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000122070

SMART Domains

Protein: ENSMUSP00000113166
Gene: ENSMUSG00000039804

Domain	Start	End	E-Value	Type
low complexity region	46	79	N/A	INTRINSIC
low complexity region	82	104	N/A	INTRINSIC
low complexity region	107	118	N/A	INTRINSIC
coiled coil region	163	190	N/A	INTRINSIC
SCOP:d1kmma1	195	287	1e-8	SMART
PDB:1V95\|A	197	314	2e-80	PDB
low complexity region	324	340	N/A	INTRINSIC
low complexity region	367	376	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000137302

Predicted Effect

probably damaging
Transcript: ENSMUST00000202223
AA Change: R1072W

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000143870
Gene: ENSMUSG00000017740
AA Change: R1072W

Domain	Start	End	E-Value	Type
low complexity region	11	19	N/A	INTRINSIC
low complexity region	100	113	N/A	INTRINSIC
Pfam:AA_permease	125	327	1e-19	PFAM
Pfam:AA_permease_2	386	655	4.5e-15	PFAM
Pfam:AA_permease	412	699	3.7e-40	PFAM
Pfam:SLC12	711	837	7.2e-17	PFAM
Pfam:SLC12	830	982	6.2e-18	PFAM
low complexity region	1001	1025	N/A	INTRINSIC
Pfam:SLC12	1030	1133	8.6e-13	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000202479

SMART Domains

Protein: ENSMUSP00000144540
Gene: ENSMUSG00000017740

Domain	Start	End	E-Value	Type
low complexity region	10	22	N/A	INTRINSIC
low complexity region	77	90	N/A	INTRINSIC
Pfam:AA_permease	102	176	5.2e-10	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000202623
AA Change: R1077W

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000144623
Gene: ENSMUSG00000017740
AA Change: R1077W

Domain	Start	End	E-Value	Type
low complexity region	11	19	N/A	INTRINSIC
low complexity region	100	113	N/A	INTRINSIC
Pfam:AA_permease	125	327	5.3e-22	PFAM
Pfam:AA_permease_2	386	655	1.2e-17	PFAM
Pfam:AA_permease	412	699	2e-42	PFAM
Pfam:SLC12	711	837	2.1e-19	PFAM
Pfam:SLC12	830	982	1.8e-20	PFAM
low complexity region	1001	1025	N/A	INTRINSIC
Pfam:SLC12	1032	1138	2.2e-15	PFAM

Coding Region Coverage

1x: 99.2%
3x: 98.7%
10x: 97.4%
20x: 95.5%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] K-Cl cotransporters are proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The protein encoded by this gene is an integral membrane K-Cl cotransporter that can function in either a net efflux or influx pathway, depending on the chemical concentration gradients of potassium and chloride. The encoded protein can act as a homomultimer, or as a heteromultimer with other K-Cl cotransporters, to maintain chloride homeostasis in neurons. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Sep 2008]
PHENOTYPE: Mice homozygous for disruptions in this gene die within a few minutes of birth of respiratory failure resulting from a motor nerve defect. Mice homozygous for a hypomorphic allele display postnatal lethality and tonic-clonic seizures. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 89 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4933436I01Rik	T	A	X: 67,920,702	I184L	probably benign	Het
9530002B09Rik	T	A	4: 122,689,322		probably benign	Het
Abca15	A	T	7: 120,360,904	T637S	possibly damaging	Het
Adgrv1	T	C	13: 81,561,469	K1135R	possibly damaging	Het
Afap1l1	A	T	18: 61,739,122		probably null	Het
AI467606	A	G	7: 127,092,837	S195G	probably damaging	Het
Alox12e	G	A	11: 70,316,002	R620W	probably damaging	Het
Ascc2	A	T	11: 4,681,496	M646L	probably benign	Het
Ccnt1	A	T	15: 98,551,942	H156Q	probably benign	Het
Cic	T	A	7: 25,273,451	V869E	probably damaging	Het
Cpsf2	A	G	12: 101,983,463	D118G	probably damaging	Het
Csnk1g1	A	G	9: 66,002,230	S210G	probably damaging	Het
Cyp2c40	T	A	19: 39,786,780	M343L	probably benign	Het
Cyp4a12b	A	T	4: 115,433,503	D274V	possibly damaging	Het
Dnaaf3	T	C	7: 4,523,799	I426M	possibly damaging	Het
Dnah3	C	T	7: 119,951,909	M3062I	probably damaging	Het
Dtx2	C	T	5: 136,030,577	S493F	probably damaging	Het
Elavl2	A	T	4: 91,253,450	S278R	possibly damaging	Het
Emilin2	T	C	17: 71,274,955	S259G	probably benign	Het
Endov	T	C	11: 119,499,582	F12S	probably damaging	Het
Faim2	G	A	15: 99,514,433	T140I	probably damaging	Het
Fbxo21	T	C	5: 117,976,966	S56P	probably benign	Het
Fgb	C	A	3: 83,049,689	D25Y	probably benign	Het
Foxj2	A	T	6: 122,840,241	H509L	probably benign	Het
Fth1	T	A	19: 9,984,212	L49Q	probably damaging	Het
Gbp11	C	A	5: 105,328,584	E220*	probably null	Het
Gm12695	T	C	4: 96,769,726	T69A	probably benign	Het
Gm1527	C	A	3: 28,926,647	T632N	probably benign	Het
Gm4787	A	T	12: 81,378,920	S155T	probably benign	Het
Gm9573	T	A	17: 35,621,405		probably benign	Het
Gtf2f2	A	G	14: 75,917,696	S142P	possibly damaging	Het
Helb	T	C	10: 120,105,766	Y339C	probably benign	Het
Hs3st4	A	G	7: 124,397,013	I301V	probably benign	Het
Hunk	A	G	16: 90,493,480	D382G	probably damaging	Het
Ifnb1	T	A	4: 88,522,759	I6F	possibly damaging	Het
Il10	T	C	1: 131,020,033	L41P	probably damaging	Het
Il2rg	A	G	X: 101,267,810	L57P	possibly damaging	Het
Invs	T	A	4: 48,396,287	L320Q	probably damaging	Het
Itpr3	G	A	17: 27,098,076	M768I	probably benign	Het
Krt90	T	C	15: 101,558,359	E263G	probably benign	Het
Lama2	C	T	10: 27,164,926	C1467Y	probably damaging	Het
Med24	A	G	11: 98,715,646	L330P	probably damaging	Het
Mrto4	T	C	4: 139,349,023	K86E	probably benign	Het
Mtcl1	T	C	17: 66,346,355	R1065G	probably damaging	Het
Mtmr14	G	A	6: 113,240,361	G38D	probably damaging	Het
Mtus1	T	C	8: 41,082,708	E657G	probably damaging	Het
Myo5c	A	T	9: 75,281,868	Q1020L	probably benign	Het
Nav1	C	T	1: 135,449,004	R1694Q	probably damaging	Het
Nckap1	T	C	2: 80,570,150	K69R	probably damaging	Het
Nlrp1b	T	C	11: 71,161,086	N1012D	probably benign	Het
Ntrk2	A	C	13: 58,859,297	K238Q	probably damaging	Het
Oas1g	T	C	5: 120,885,883	E121G	probably damaging	Het
Olfr324	A	G	11: 58,597,570	N58S	probably damaging	Het
Olfr667	T	C	7: 104,916,775	N174D	probably benign	Het
Pcdh8	A	T	14: 79,768,211	S912R	probably damaging	Het
Pfpl	C	T	19: 12,429,873	S496L	probably damaging	Het
Phc2	T	C	4: 128,747,136	F672S	probably damaging	Het
Pkhd1l1	A	T	15: 44,550,752	H2805L	possibly damaging	Het
Pla2g4a	T	C	1: 149,840,676	N678S	possibly damaging	Het
Plxnb3	T	A	X: 73,771,751	Y1845*	probably null	Het
Polr1a	T	G	6: 71,936,285		probably null	Het
Prl3d3	A	C	13: 27,162,321	E180D	probably benign	Het
Prl7a2	T	A	13: 27,660,887	Y172F	probably damaging	Het
Prpf3	A	T	3: 95,844,239	D383E	probably benign	Het
Psmc4	A	T	7: 28,048,897	L73H	probably damaging	Het
Rapgef3	C	A	15: 97,766,961	G7V	probably damaging	Het
Rasl12	G	A	9: 65,410,824	G157R	probably damaging	Het
Rnf38	A	C	4: 44,149,098	V83G	probably damaging	Het
Rnls	A	C	19: 33,202,544	S51A	probably benign	Het
Siglecf	A	G	7: 43,352,380	T205A	possibly damaging	Het
Skint1	T	A	4: 112,025,533	V258D	probably benign	Het
Spata13	GTTAGGCT	GT	14: 60,760,871		probably benign	Het
Specc1	T	G	11: 62,118,296	S293A	probably benign	Het
Speer2	T	G	16: 69,860,497	Q86P	probably benign	Het
Tbc1d15	T	C	10: 115,229,173	D169G	probably benign	Het
Tbx20	C	A	9: 24,769,771	E142*	probably null	Het
Tcp1	T	A	17: 12,920,812	L199H	probably damaging	Het
Tex26	A	T	5: 149,439,739	R5W	probably damaging	Het
Tg	C	A	15: 66,828,553	A120E	probably damaging	Het
Thrap3	T	C	4: 126,175,396	Y654C	possibly damaging	Het
Tmem57	A	T	4: 134,828,279	N294K	possibly damaging	Het
Troap	T	C	15: 99,082,463	L508P	probably benign	Het
Ubap2	C	T	4: 41,199,872	A752T	probably benign	Het
Ush1c	T	C	7: 46,229,481	Y74C	probably damaging	Het
Vmn1r55	A	G	7: 5,147,049	V125A	possibly damaging	Het
Vmn2r120	T	A	17: 57,524,553	H412L	possibly damaging	Het
Vps54	C	T	11: 21,277,955	T176I	probably damaging	Het
Wdr95	T	C	5: 149,579,162		probably null	Het
Zfp81	T	C	17: 33,335,304	T179A	probably benign	Het

Other mutations in Slc12a5

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00324:Slc12a5	APN	2	164997121	missense	probably damaging	1.00
IGL00425:Slc12a5	APN	2	164983281	missense	probably damaging	1.00
IGL00976:Slc12a5	APN	2	164979304	missense	probably damaging	1.00
IGL01654:Slc12a5	APN	2	164973755	missense	possibly damaging	0.91
IGL01905:Slc12a5	APN	2	164990381	missense	probably benign	0.02
IGL02205:Slc12a5	APN	2	164996479	missense	probably benign	0.03
IGL02510:Slc12a5	APN	2	164982808	splice site	probably benign
IGL02746:Slc12a5	APN	2	164974916	missense	probably benign	0.01
G1Funyon:Slc12a5	UTSW	2	164993691	missense	probably damaging	0.98
R0051:Slc12a5	UTSW	2	164986663	missense	probably damaging	1.00
R0254:Slc12a5	UTSW	2	164997245	critical splice donor site	probably null
R0412:Slc12a5	UTSW	2	164994062	missense	probably benign	0.05
R0587:Slc12a5	UTSW	2	164976533	missense	probably damaging	1.00
R0835:Slc12a5	UTSW	2	164994038	missense	probably damaging	0.97
R0932:Slc12a5	UTSW	2	164996885	splice site	probably benign
R1643:Slc12a5	UTSW	2	164994027	missense	probably benign	0.01
R1700:Slc12a5	UTSW	2	164992376	missense	possibly damaging	0.94
R1760:Slc12a5	UTSW	2	164996128	missense	probably damaging	0.99
R2293:Slc12a5	UTSW	2	164992330	missense	probably benign	0.03
R2412:Slc12a5	UTSW	2	164976462	critical splice donor site	probably null
R3035:Slc12a5	UTSW	2	164980258	missense	probably benign	0.06
R3116:Slc12a5	UTSW	2	164996181	splice site	probably null
R3412:Slc12a5	UTSW	2	164968431	missense	probably benign	0.26
R3788:Slc12a5	UTSW	2	164993775	missense	probably damaging	1.00
R4039:Slc12a5	UTSW	2	164992330	missense	probably benign	0.03
R4174:Slc12a5	UTSW	2	164979490	missense	probably damaging	1.00
R4492:Slc12a5	UTSW	2	164979343	missense	probably benign	0.08
R4608:Slc12a5	UTSW	2	164973765	missense	probably damaging	0.99
R4750:Slc12a5	UTSW	2	164982931	missense	probably benign	0.06
R4994:Slc12a5	UTSW	2	164983365	splice site	probably null
R5103:Slc12a5	UTSW	2	164992433	missense	probably damaging	1.00
R5539:Slc12a5	UTSW	2	164987206	missense	possibly damaging	0.94
R5632:Slc12a5	UTSW	2	164987221	missense	possibly damaging	0.86
R5771:Slc12a5	UTSW	2	164973768	missense	possibly damaging	0.88
R6139:Slc12a5	UTSW	2	164992311	missense	probably damaging	0.98
R6336:Slc12a5	UTSW	2	164992464	splice site	probably null
R6581:Slc12a5	UTSW	2	164987115	missense	probably damaging	1.00
R6706:Slc12a5	UTSW	2	164988589	missense	probably damaging	1.00
R6886:Slc12a5	UTSW	2	164982905	missense	probably benign
R7134:Slc12a5	UTSW	2	164974958	missense	probably damaging	1.00
R7310:Slc12a5	UTSW	2	164992440	missense	probably damaging	1.00
R7402:Slc12a5	UTSW	2	164982932	missense	probably benign	0.01
R8079:Slc12a5	UTSW	2	164992452	missense	probably damaging	1.00
R8301:Slc12a5	UTSW	2	164993691	missense	probably damaging	0.98
R9105:Slc12a5	UTSW	2	164996194	missense	probably benign
R9132:Slc12a5	UTSW	2	164993956	intron	probably benign
R9431:Slc12a5	UTSW	2	164990258	missense	possibly damaging	0.95
R9580:Slc12a5	UTSW	2	164974976	missense	probably damaging	0.99

Predicted Primers

PCR Primer
(F):5'- TAGGTTTCTAGGGTCCCTCC -3'
(R):5'- TTTCATCCCAGGCTAGAGGACC -3'

Sequencing Primer
(F):5'- CATTGCCCAGCTTGGAGTG -3'
(R):5'- GCTAGAGGACCCACGTAATG -3'

Posted On

2014-09-17