Mutagenetix > Incidental Mutation

Incidental Mutation 'R7402:Slc12a5'

574242

Institutional Source

Beutler Lab

Gene Symbol

Slc12a5

Ensembl Gene

ENSMUSG00000017740

Gene Name

solute carrier family 12, member 5

Synonyms

KCC2

MMRRC Submission

045484-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7402 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

164802766-164841651 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 164824852 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Lysine at position 419 (M419K)

Ref Sequence

ENSEMBL: ENSMUSP00000144623 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000099092] [ENSMUST00000202136] [ENSMUST00000202223] [ENSMUST00000202479] [ENSMUST00000202623]

AlphaFold

Q91V14

Predicted Effect

possibly damaging
Transcript: ENSMUST00000099092
AA Change: M396K

PolyPhen 2 Score 0.640 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000096690
Gene: ENSMUSG00000017740
AA Change: M396K

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: ENSMUST00000202136

SMART Domains

Protein: ENSMUSP00000143973
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	175	2.5e-10	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000202223
AA Change: M419K

PolyPhen 2 Score 0.539 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000143870
Gene: ENSMUSG00000017740
AA Change: M419K

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 benign
Transcript: ENSMUST00000202623
AA Change: M419K

PolyPhen 2 Score 0.015 (Sensitivity: 0.96; Specificity: 0.79)

SMART Domains

Protein: ENSMUSP00000144623
Gene: ENSMUSG00000017740
AA Change: M419K

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: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.3%

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: 98 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc4	G	T	14: 118,943,487 (GRCm39)	P12Q	probably damaging	Het
Acsf3	A	G	8: 123,507,163 (GRCm39)	Y152C	probably damaging	Het
Adam22	T	A	5: 8,145,049 (GRCm39)	Q803L	possibly damaging	Het
Adamtsl3	G	A	7: 82,227,825 (GRCm39)	V1337I	probably damaging	Het
Adra1b	T	C	11: 43,666,845 (GRCm39)	D464G	possibly damaging	Het
Alpk3	T	A	7: 80,726,660 (GRCm39)	I115K	probably benign	Het
Amdhd2	A	G	17: 24,380,657 (GRCm39)	S96P		Het
Ankib1	T	G	5: 3,819,586 (GRCm39)	D111A	probably benign	Het
Arhgef2	A	G	3: 88,540,873 (GRCm39)	D216G	probably damaging	Het
Astn1	A	T	1: 158,380,425 (GRCm39)		probably benign	Het
Atosa	C	A	9: 74,913,668 (GRCm39)	Y107*	probably null	Het
Atrn	T	A	2: 130,789,520 (GRCm39)	W328R	probably damaging	Het
Atxn7	A	T	14: 14,095,427 (GRCm38)	H375L	probably damaging	Het
Btaf1	A	T	19: 36,980,915 (GRCm39)	N1579Y	probably damaging	Het
Cacna1b	A	T	2: 24,497,671 (GRCm39)	L2079Q	probably benign	Het
Ccdc102a	T	C	8: 95,629,981 (GRCm39)	K520R	probably damaging	Het
Cd2ap	T	C	17: 43,116,054 (GRCm39)	H602R	possibly damaging	Het
Cdkn2aip	A	G	8: 48,164,408 (GRCm39)	V435A	possibly damaging	Het
Cenpf	A	T	1: 189,391,575 (GRCm39)	Y735*	probably null	Het
Cep350	T	A	1: 155,803,961 (GRCm39)	I1041L	probably benign	Het
Ckap4	A	G	10: 84,363,863 (GRCm39)	V400A	probably damaging	Het
Comp	T	A	8: 70,829,854 (GRCm39)	D359E	probably benign	Het
Coq10b	A	C	1: 55,100,500 (GRCm39)	K61N	probably benign	Het
Csmd2	G	A	4: 128,215,889 (GRCm39)	S548N		Het
Csmd2	A	C	4: 128,215,888 (GRCm39)	S548R		Het
Ctif	A	G	18: 75,744,807 (GRCm39)	I99T	probably benign	Het
Ctns	T	G	11: 73,083,903 (GRCm39)	T40P	possibly damaging	Het
Cyp11b1	C	T	15: 74,712,674 (GRCm39)	R129H	probably damaging	Het
Cyp2c68	A	T	19: 39,729,318 (GRCm39)	N56K	probably benign	Het
D6Wsu163e	A	G	6: 126,938,968 (GRCm39)	K401R	probably damaging	Het
Dstn	T	A	2: 143,780,368 (GRCm39)	C23S	probably benign	Het
Fam72a	A	T	1: 131,466,613 (GRCm39)	E132D	probably damaging	Het
Fam72a	G	T	1: 131,466,614 (GRCm39)	E133*	probably null	Het
Gbp8	T	A	5: 105,179,161 (GRCm39)	I113F	probably damaging	Het
Gm3095	A	T	14: 15,170,332 (GRCm39)	R60S	possibly damaging	Het
Gpa33	A	T	1: 165,980,263 (GRCm39)	M109L	probably damaging	Het
Grik2	A	G	10: 49,411,493 (GRCm39)	L215P	probably damaging	Het
Gucy2g	A	C	19: 55,194,725 (GRCm39)	F897L	probably damaging	Het
Hinfp	A	G	9: 44,209,314 (GRCm39)	L295P	probably damaging	Het
Ift122	T	C	6: 115,871,283 (GRCm39)	V526A	probably benign	Het
Ighv5-12	T	C	12: 113,665,853 (GRCm39)	T82A	probably benign	Het
Il18rap	T	A	1: 40,564,111 (GRCm39)	S76R	probably benign	Het
Itga6	A	T	2: 71,683,897 (GRCm39)	N1045I	probably benign	Het
Kctd21	A	T	7: 96,996,970 (GRCm39)	I148F	possibly damaging	Het
Kif28	T	A	1: 179,567,644 (GRCm39)	H42L	probably benign	Het
Kmt2c	A	C	5: 25,600,418 (GRCm39)	C326W	probably damaging	Het
Knl1	T	A	2: 118,925,707 (GRCm39)	L1912*	probably null	Het
Lrfn1	A	T	7: 28,158,947 (GRCm39)	I289F	probably damaging	Het
Lrriq1	T	C	10: 103,057,185 (GRCm39)	K205R	possibly damaging	Het
Mbd5	A	T	2: 49,147,566 (GRCm39)	N592I	probably damaging	Het
Mbl2	A	G	19: 30,216,802 (GRCm39)	N205D	possibly damaging	Het
Mcm4	C	A	16: 15,455,042 (GRCm39)	M1I	probably null	Het
Mgat4a	T	A	1: 37,493,865 (GRCm39)	H327L	probably damaging	Het
Miox	A	G	15: 89,219,206 (GRCm39)	D16G	probably benign	Het
Mvk	C	A	5: 114,594,039 (GRCm39)	P298Q	possibly damaging	Het
Nol6	A	G	4: 41,118,699 (GRCm39)	L726P	probably damaging	Het
Nos1	T	C	5: 118,087,880 (GRCm39)	I1381T	probably benign	Het
Nup98	A	T	7: 101,784,144 (GRCm39)	S1063T	probably benign	Het
Obscn	T	G	11: 58,886,275 (GRCm39)	M7862L	unknown	Het
Obsl1	T	C	1: 75,464,348 (GRCm39)	T1653A	probably benign	Het
Odr4	A	G	1: 150,262,107 (GRCm39)		probably null	Het
Or4c105	G	T	2: 88,647,687 (GRCm39)	M57I	probably damaging	Het
Or8g53	T	A	9: 39,683,260 (GRCm39)	T279S	probably benign	Het
Or8u9	A	G	2: 86,001,546 (GRCm39)	I205T	probably benign	Het
Or9q2	C	T	19: 13,772,358 (GRCm39)	V206I	probably damaging	Het
Pcdhb20	A	G	18: 37,638,005 (GRCm39)	Y177C	probably benign	Het
Pcdhb3	A	C	18: 37,434,657 (GRCm39)	I208L	probably benign	Het
Phlpp1	G	T	1: 106,317,420 (GRCm39)	G1214W	probably damaging	Het
Ppp4r3a	A	T	12: 101,025,053 (GRCm39)	S149T	possibly damaging	Het
Pxdn	T	C	12: 30,052,438 (GRCm39)	C872R	probably damaging	Het
Rarb	A	G	14: 16,548,419 (GRCm38)	C101R	probably damaging	Het
Rcor3	A	C	1: 191,812,283 (GRCm39)	V114G	probably benign	Het
Rnpepl1	A	G	1: 92,847,372 (GRCm39)	Q653R	probably benign	Het
Rpap2	T	A	5: 107,768,324 (GRCm39)	Y387*	probably null	Het
Rttn	C	T	18: 89,004,035 (GRCm39)	T343M	possibly damaging	Het
Samd11	T	C	4: 156,333,230 (GRCm39)	T333A	probably benign	Het
Six5	T	C	7: 18,828,968 (GRCm39)	L136P	probably damaging	Het
Slc22a21	T	C	11: 53,851,226 (GRCm39)	M179V	probably benign	Het
Slc35a4	A	G	18: 36,813,570 (GRCm39)	D6G	unknown	Het
Spdye4c	A	T	2: 128,434,261 (GRCm39)	M1L	probably benign	Het
Svep1	A	T	4: 58,069,699 (GRCm39)	C2696S	possibly damaging	Het
Tceanc2	T	C	4: 107,004,893 (GRCm39)	N85S	probably benign	Het
Teddm2	G	C	1: 153,726,344 (GRCm39)	L124V	probably benign	Het
Teddm2	A	T	1: 153,726,343 (GRCm39)	L124Q	probably damaging	Het
Tgfbr1	T	A	4: 47,405,623 (GRCm39)	W409R	probably damaging	Het
Tkt	A	G	14: 30,280,755 (GRCm39)	D62G	probably damaging	Het
Tnrc6b	T	A	15: 80,768,501 (GRCm39)	V1054D	probably damaging	Het
Trpm7	C	A	2: 126,641,126 (GRCm39)	L1564F	probably damaging	Het
Vmn1r43	A	T	6: 89,846,803 (GRCm39)	C228S	probably benign	Het
Vmn2r106	T	C	17: 20,487,883 (GRCm39)	R839G	probably damaging	Het
Vmn2r5	G	A	3: 64,403,176 (GRCm39)	T523I	probably benign	Het
Vwa3b	C	T	1: 37,153,678 (GRCm39)	Q507*	probably null	Het
Wrn	C	G	8: 33,738,994 (GRCm39)	W1278S	probably benign	Het
Zfp281	T	G	1: 136,553,190 (GRCm39)	L56R	probably damaging	Het
Zfp407	G	A	18: 84,579,661 (GRCm39)	T484I	probably benign	Het
Zfp451	T	C	1: 33,852,843 (GRCm39)	T24A	probably benign	Het
Zfp607b	T	A	7: 27,392,919 (GRCm39)	F16I	probably damaging	Het
Zfp638	T	A	6: 83,905,670 (GRCm39)	V41E	possibly damaging	Het

Other mutations in Slc12a5

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00324:Slc12a5	APN	2	164,839,041 (GRCm39)	missense	probably damaging	1.00
IGL00425:Slc12a5	APN	2	164,825,201 (GRCm39)	missense	probably damaging	1.00
IGL00976:Slc12a5	APN	2	164,821,224 (GRCm39)	missense	probably damaging	1.00
IGL01654:Slc12a5	APN	2	164,815,675 (GRCm39)	missense	possibly damaging	0.91
IGL01905:Slc12a5	APN	2	164,832,301 (GRCm39)	missense	probably benign	0.02
IGL02205:Slc12a5	APN	2	164,838,399 (GRCm39)	missense	probably benign	0.03
IGL02510:Slc12a5	APN	2	164,824,728 (GRCm39)	splice site	probably benign
IGL02746:Slc12a5	APN	2	164,816,836 (GRCm39)	missense	probably benign	0.01
G1Funyon:Slc12a5	UTSW	2	164,835,611 (GRCm39)	missense	probably damaging	0.98
R0051:Slc12a5	UTSW	2	164,828,583 (GRCm39)	missense	probably damaging	1.00
R0254:Slc12a5	UTSW	2	164,839,165 (GRCm39)	critical splice donor site	probably null
R0412:Slc12a5	UTSW	2	164,835,982 (GRCm39)	missense	probably benign	0.05
R0587:Slc12a5	UTSW	2	164,818,453 (GRCm39)	missense	probably damaging	1.00
R0835:Slc12a5	UTSW	2	164,835,958 (GRCm39)	missense	probably damaging	0.97
R0932:Slc12a5	UTSW	2	164,838,805 (GRCm39)	splice site	probably benign
R1643:Slc12a5	UTSW	2	164,835,947 (GRCm39)	missense	probably benign	0.01
R1700:Slc12a5	UTSW	2	164,834,296 (GRCm39)	missense	possibly damaging	0.94
R1760:Slc12a5	UTSW	2	164,838,048 (GRCm39)	missense	probably damaging	0.99
R2063:Slc12a5	UTSW	2	164,839,067 (GRCm39)	missense	probably damaging	1.00
R2293:Slc12a5	UTSW	2	164,834,250 (GRCm39)	missense	probably benign	0.03
R2412:Slc12a5	UTSW	2	164,818,382 (GRCm39)	critical splice donor site	probably null
R3035:Slc12a5	UTSW	2	164,822,178 (GRCm39)	missense	probably benign	0.06
R3116:Slc12a5	UTSW	2	164,838,101 (GRCm39)	splice site	probably null
R3412:Slc12a5	UTSW	2	164,810,351 (GRCm39)	missense	probably benign	0.26
R3788:Slc12a5	UTSW	2	164,835,695 (GRCm39)	missense	probably damaging	1.00
R4039:Slc12a5	UTSW	2	164,834,250 (GRCm39)	missense	probably benign	0.03
R4174:Slc12a5	UTSW	2	164,821,410 (GRCm39)	missense	probably damaging	1.00
R4492:Slc12a5	UTSW	2	164,821,263 (GRCm39)	missense	probably benign	0.08
R4608:Slc12a5	UTSW	2	164,815,685 (GRCm39)	missense	probably damaging	0.99
R4750:Slc12a5	UTSW	2	164,824,851 (GRCm39)	missense	probably benign	0.06
R4994:Slc12a5	UTSW	2	164,825,285 (GRCm39)	splice site	probably null
R5103:Slc12a5	UTSW	2	164,834,353 (GRCm39)	missense	probably damaging	1.00
R5539:Slc12a5	UTSW	2	164,829,126 (GRCm39)	missense	possibly damaging	0.94
R5632:Slc12a5	UTSW	2	164,829,141 (GRCm39)	missense	possibly damaging	0.86
R5771:Slc12a5	UTSW	2	164,815,688 (GRCm39)	missense	possibly damaging	0.88
R6139:Slc12a5	UTSW	2	164,834,231 (GRCm39)	missense	probably damaging	0.98
R6336:Slc12a5	UTSW	2	164,834,384 (GRCm39)	splice site	probably null
R6581:Slc12a5	UTSW	2	164,829,035 (GRCm39)	missense	probably damaging	1.00
R6706:Slc12a5	UTSW	2	164,830,509 (GRCm39)	missense	probably damaging	1.00
R6886:Slc12a5	UTSW	2	164,824,825 (GRCm39)	missense	probably benign
R7134:Slc12a5	UTSW	2	164,816,878 (GRCm39)	missense	probably damaging	1.00
R7310:Slc12a5	UTSW	2	164,834,360 (GRCm39)	missense	probably damaging	1.00
R8079:Slc12a5	UTSW	2	164,834,372 (GRCm39)	missense	probably damaging	1.00
R8301:Slc12a5	UTSW	2	164,835,611 (GRCm39)	missense	probably damaging	0.98
R9105:Slc12a5	UTSW	2	164,838,114 (GRCm39)	missense	probably benign
R9132:Slc12a5	UTSW	2	164,835,876 (GRCm39)	intron	probably benign
R9431:Slc12a5	UTSW	2	164,832,178 (GRCm39)	missense	possibly damaging	0.95
R9580:Slc12a5	UTSW	2	164,816,896 (GRCm39)	missense	probably damaging	0.99
R9677:Slc12a5	UTSW	2	164,834,246 (GRCm39)	missense	possibly damaging	0.66

Predicted Primers

PCR Primer
(F):5'- ATGCCCTGGTACAAAGCAG -3'
(R):5'- ACAACCAGTTCCGGCTTAGG -3'

Sequencing Primer
(F):5'- TCCTGGTCTGAGCTCTGGC -3'
(R):5'- CTTAGGTGGCAGGGTCATCAAAC -3'

Posted On

2019-09-13