Mutagenetix > Incidental Mutation

Incidental Mutation 'R7134:Slc12a5'

552887

Institutional Source

Beutler Lab

Gene Symbol

Slc12a5

Ensembl Gene

ENSMUSG00000017740

Gene Name

solute carrier family 12, member 5

Synonyms

KCC2

MMRRC Submission

045219-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7134 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

164802766-164841651 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 164816878 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Phenylalanine at position 134 (I134F)

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: I111F

PolyPhen 2 Score 0.599 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000096690
Gene: ENSMUSG00000017740
AA Change: I111F

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 damaging
Transcript: ENSMUST00000202136
AA Change: I111F

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000143973
Gene: ENSMUSG00000017740
AA Change: I111F

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

probably damaging
Transcript: ENSMUST00000202223
AA Change: I134F

PolyPhen 2 Score 0.981 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000143870
Gene: ENSMUSG00000017740
AA Change: I134F

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 damaging
Transcript: ENSMUST00000202479
AA Change: I111F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000144540
Gene: ENSMUSG00000017740
AA Change: I111F

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: I134F

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000144623
Gene: ENSMUSG00000017740
AA Change: I134F

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: 99.9%
10x: 99.7%
20x: 99.1%

Validation Efficiency

99% (84/85)

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: 86 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcf1	A	G	17: 36,270,144 (GRCm39)	F638S	possibly damaging	Het
Actl6b	T	A	5: 137,562,762 (GRCm39)	N159K	probably damaging	Het
Adam6a	T	G	12: 113,508,655 (GRCm39)	S343A	probably benign	Het
Ankrd17	G	A	5: 90,380,173 (GRCm39)	T2505I	probably damaging	Het
Ankrd17	T	C	5: 90,433,382 (GRCm39)	T728A	probably benign	Het
Asap2	G	T	12: 21,315,964 (GRCm39)	E919*	probably null	Het
Atp10b	A	T	11: 43,136,291 (GRCm39)	I1140F	probably damaging	Het
Cep126	A	T	9: 8,103,383 (GRCm39)	V209E	probably damaging	Het
Cfap65	C	T	1: 74,965,792 (GRCm39)	R406Q	probably benign	Het
Cldn1	T	C	16: 26,190,376 (GRCm39)	M1V	probably null	Het
Cryl1	C	T	14: 57,512,956 (GRCm39)	D304N	probably benign	Het
D3Ertd751e	T	C	3: 41,708,212 (GRCm39)		probably null	Het
D630044L22Rik	A	T	17: 26,181,090 (GRCm39)	M156L	probably benign	Het
Ddx21	T	C	10: 62,427,634 (GRCm39)	D423G	possibly damaging	Het
Dock2	T	A	11: 34,260,363 (GRCm39)	M993L	probably benign	Het
Dusp29	A	T	14: 21,727,129 (GRCm39)	I173N	probably damaging	Het
Eif4g1	C	T	16: 20,500,252 (GRCm39)	A675V	probably damaging	Het
Eml1	C	T	12: 108,472,810 (GRCm39)	S206L	probably benign	Het
Farp2	A	C	1: 93,531,181 (GRCm39)	I560L	probably benign	Het
Fbn1	A	T	2: 125,223,969 (GRCm39)	D593E	probably benign	Het
Fetub	A	G	16: 22,748,007 (GRCm39)	D61G	possibly damaging	Het
Fpgs	T	C	2: 32,576,641 (GRCm39)	K329E	probably benign	Het
Fpgt	T	C	3: 154,797,120 (GRCm39)	Y45C	probably damaging	Het
Gas2l1	A	T	11: 5,011,106 (GRCm39)	C574*	probably null	Het
Gm9747	G	T	1: 82,211,837 (GRCm39)	C12F	unknown	Het
H2-T23	T	C	17: 36,342,709 (GRCm39)	Y143C	probably damaging	Het
Hhip	A	T	8: 80,719,142 (GRCm39)	S462T	probably benign	Het
Hnf1a	C	T	5: 115,091,446 (GRCm39)	G416R	probably damaging	Het
Hoxa5	C	T	6: 52,181,023 (GRCm39)	C103Y	probably damaging	Het
Kansl3	G	T	1: 36,390,848 (GRCm39)	D395E	possibly damaging	Het
Marchf10	A	G	11: 105,299,502 (GRCm39)	S116P	probably benign	Het
Med12l	C	T	3: 59,001,180 (GRCm39)	Q748*	probably null	Het
Mroh7	T	A	4: 106,577,791 (GRCm39)	N296Y	probably damaging	Het
Mtbp	T	G	15: 55,421,961 (GRCm39)	D61E	probably benign	Het
Muc5b	A	T	7: 141,411,391 (GRCm39)	I1446L	unknown	Het
Myh15	T	C	16: 48,901,705 (GRCm39)	V266A	possibly damaging	Het
Nap1l1	G	A	10: 111,330,655 (GRCm39)		probably null	Het
Napsa	A	G	7: 44,235,159 (GRCm39)	T315A	probably benign	Het
Nlrc5	A	T	8: 95,206,350 (GRCm39)	I734F	probably damaging	Het
Nnt	A	G	13: 119,531,198 (GRCm39)	V183A	probably damaging	Het
Nploc4	A	T	11: 120,276,614 (GRCm39)	D477E	probably benign	Het
Nrip3	A	G	7: 109,364,695 (GRCm39)	S144P	probably damaging	Het
Ntng1	A	T	3: 109,842,445 (GRCm39)	F109L	probably benign	Het
Or5p61	A	G	7: 107,758,883 (GRCm39)	Y66H	probably damaging	Het
Or5v1	T	A	17: 37,809,776 (GRCm39)	V78D	probably damaging	Het
Or6aa1	G	A	7: 86,044,752 (GRCm39)		probably benign	Het
Or8b36	A	G	9: 37,937,795 (GRCm39)	E231G	probably benign	Het
Pacsin1	G	A	17: 27,921,707 (GRCm39)	D30N	probably damaging	Het
Pbld2	A	T	10: 62,860,368 (GRCm39)		probably benign	Het
Pcnx4	C	T	12: 72,613,750 (GRCm39)	T565I	probably damaging	Het
Pdzk1	A	T	3: 96,763,246 (GRCm39)	T225S	probably benign	Het
Phyhip	T	G	14: 70,704,639 (GRCm39)	I286S	probably benign	Het
Pkd1	T	A	17: 24,813,086 (GRCm39)	Y3903N	probably damaging	Het
Plcb3	A	T	19: 6,942,698 (GRCm39)	L222Q	probably damaging	Het
Plcd4	T	A	1: 74,593,662 (GRCm39)	H262Q	probably benign	Het
Plekhh1	C	T	12: 79,109,390 (GRCm39)	A474V	probably benign	Het
Plppr3	T	C	10: 79,701,537 (GRCm39)	E435G	probably damaging	Het
Poln	T	A	5: 34,276,340 (GRCm39)	N305I	possibly damaging	Het
Pou3f2	T	C	4: 22,486,874 (GRCm39)	T420A	probably benign	Het
Ppdpf	T	C	2: 180,829,523 (GRCm39)	Y17H	probably damaging	Het
Prrx2	C	A	2: 30,768,485 (GRCm39)	T104K	probably damaging	Het
Ptprj	A	T	2: 90,294,822 (GRCm39)	L462H	probably benign	Het
Radil	T	C	5: 142,471,304 (GRCm39)	T991A	probably damaging	Het
Rbsn	T	C	6: 92,178,608 (GRCm39)	E147G	probably damaging	Het
Ror2	C	T	13: 53,300,742 (GRCm39)	V35M	probably benign	Het
Rps6ka1	T	C	4: 133,599,373 (GRCm39)	Q18R	probably benign	Het
Setbp1	T	A	18: 78,902,734 (GRCm39)	D311V	possibly damaging	Het
Setd2	C	T	9: 110,377,865 (GRCm39)	S560L	possibly damaging	Het
Speer1h	C	T	5: 11,647,706 (GRCm39)	T148I	possibly damaging	Het
Svil	A	G	18: 5,116,080 (GRCm39)	D2035G	probably damaging	Het
Syngap1	T	C	17: 27,178,985 (GRCm39)	Y665H	probably damaging	Het
Tbc1d9b	T	C	11: 50,043,519 (GRCm39)	Y547H	possibly damaging	Het
Tgm2	A	G	2: 157,980,812 (GRCm39)	V83A	probably benign	Het
Tmem233	T	C	5: 116,189,429 (GRCm39)	I117V	probably benign	Het
Tsen34	A	G	7: 3,703,640 (GRCm39)	T293A	probably damaging	Het
Ttn	A	G	2: 76,709,023 (GRCm39)	V8752A	unknown	Het
Ubac1	A	G	2: 25,904,974 (GRCm39)	V88A	probably benign	Het
Uchl4	T	C	9: 64,142,621 (GRCm39)	V34A	probably damaging	Het
Ugt2a2	C	T	5: 87,608,435 (GRCm39)	R468H	probably benign	Het
Vmn2r102	A	T	17: 19,897,749 (GRCm39)	T255S	probably benign	Het
Wdr6	T	A	9: 108,450,564 (GRCm39)	N988I	probably damaging	Het
Wnk1	A	T	6: 119,903,389 (GRCm39)	I2359N	unknown	Het
Ybey	A	G	10: 76,304,025 (GRCm39)	V59A	probably benign	Het
Zfp268	T	A	4: 145,349,375 (GRCm39)	C271S	possibly damaging	Het
Zfp397	A	G	18: 24,090,122 (GRCm39)	N142S	probably benign	Het
Zfy1	A	T	Y: 725,788 (GRCm39)	V659E	probably 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
R7310:Slc12a5	UTSW	2	164,834,360 (GRCm39)	missense	probably damaging	1.00
R7402:Slc12a5	UTSW	2	164,824,852 (GRCm39)	missense	probably benign	0.01
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'- AGCATGTGAGAACCTGGGG -3'
(R):5'- AAGCTCAGGTCGCATGCT -3'

Sequencing Primer
(F):5'- CATGTGAGAACCTGGGGGAAGAG -3'
(R):5'- AGGTCGCATGCTTCCCC -3'

Posted On

2019-05-15