Mutagenetix > Incidental Mutation

Incidental Mutation 'R7310:Slc12a5'

567476

Institutional Source

Beutler Lab

Gene Symbol

Slc12a5

Ensembl Gene

ENSMUSG00000017740

Gene Name

solute carrier family 12, member 5

Synonyms

KCC2

MMRRC Submission

045409-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7310 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

164802766-164841651 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 164834360 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Methionine at position 794 (V794M)

Ref Sequence

ENSEMBL: ENSMUSP00000144623 (fasta)

Gene Model

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

AlphaFold

Q91V14

Predicted Effect

probably damaging
Transcript: ENSMUST00000099092
AA Change: V771M

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000096690
Gene: ENSMUSG00000017740
AA Change: V771M

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

probably damaging
Transcript: ENSMUST00000202223
AA Change: V794M

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

SMART Domains

Protein: ENSMUSP00000143870
Gene: ENSMUSG00000017740
AA Change: V794M

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: V794M

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

SMART Domains

Protein: ENSMUSP00000144623
Gene: ENSMUSG00000017740
AA Change: V794M

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: 99.6%
20x: 98.8%

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: 86 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2810021J22Rik	A	T	11: 58,771,094 (GRCm39)	Q192L	possibly damaging	Het
Abat	G	A	16: 8,423,457 (GRCm39)	R250Q	probably null	Het
Abcg3	A	C	5: 105,114,632 (GRCm39)	F295C	probably benign	Het
Abl1	T	C	2: 31,690,604 (GRCm39)	S708P	possibly damaging	Het
Acap2	A	T	16: 30,926,972 (GRCm39)	Y489*	probably null	Het
Akr1c6	A	T	13: 4,486,354 (GRCm39)	M54L	probably benign	Het
Arhgap5	A	T	12: 52,589,270 (GRCm39)		probably null	Het
Asap1	A	G	15: 63,971,379 (GRCm39)		probably null	Het
Atrnl1	A	T	19: 57,630,856 (GRCm39)	N208Y	possibly damaging	Het
BC028528	CTCACTGGTTCTGTGGTCACTGGTTCTGTGGTCACTGGTTCTGTGGTCACTGGTT	CTCACTGGTTCTGTGGTCACTGGTTCTGTGGTCACTGGTTCTGTGGTCACTGGTTCTGTGGTCACTGGTT	3: 95,795,448 (GRCm39)		probably benign	Het
BC028528	GTTCTGTGGTCACTG	GTTCTGTGGTCACTGATTCTGTGGTCACTG	3: 95,795,485 (GRCm39)		probably benign	Het
BC028528	G	GGGGTCACTGGTTCTT	3: 95,795,460 (GRCm39)		probably benign	Het
BC028528	ACTGGTTCTGTGGTCACTGGTTCTGTGGTCACTGGTTCTGTGGTC	ACTGGTTCTGTGGTCCCTGGTTCTGTGGTCACTGGTTCTGTGGTCACTGGTTCTGTGGTC	3: 95,795,451 (GRCm39)		probably benign	Het
Bmi1	T	C	2: 18,689,230 (GRCm39)	S305P	probably benign	Het
Bpifc	T	A	10: 85,798,891 (GRCm39)	I431F	probably damaging	Het
C130050O18Rik	A	T	5: 139,400,993 (GRCm39)	M349L	probably benign	Het
Cacna2d1	A	T	5: 16,519,914 (GRCm39)	D428V	probably damaging	Het
Card14	A	C	11: 119,217,005 (GRCm39)	Q363P	probably null	Het
Cdca2	A	T	14: 67,950,673 (GRCm39)	L86H	probably damaging	Het
Cdh22	G	T	2: 164,954,214 (GRCm39)	S769*	probably null	Het
Cdhr17	A	G	5: 17,075,246 (GRCm39)	Y872C	possibly damaging	Het
Cep164	T	C	9: 45,686,664 (GRCm39)	E690G	probably damaging	Het
Cluh	A	G	11: 74,560,285 (GRCm39)	H1304R	probably benign	Het
Daxx	C	A	17: 34,129,435 (GRCm39)	D5E	possibly damaging	Het
Dnah7c	A	G	1: 46,636,127 (GRCm39)	M1117V	possibly damaging	Het
Entpd3	T	A	9: 120,389,821 (GRCm39)		probably null	Het
Esr1	G	A	10: 4,889,259 (GRCm39)	A386T	probably damaging	Het
Etv5	G	A	16: 22,220,487 (GRCm39)	P300L	probably benign	Het
Exoc3l	A	T	8: 106,020,340 (GRCm39)	L195Q	probably damaging	Het
Exog	T	C	9: 119,274,069 (GRCm39)	L18P	unknown	Het
Fgfr1	T	A	8: 26,052,331 (GRCm39)	V219D	probably benign	Het
Gna14	A	T	19: 16,511,113 (GRCm39)	Q54L		Het
Gnb5	T	C	9: 75,221,570 (GRCm39)	L48P	probably benign	Het
Gpbp1	A	G	13: 111,589,924 (GRCm39)	I57T	probably benign	Het
Hnrnpa1	T	A	15: 103,149,884 (GRCm39)	D48E	probably damaging	Het
Hrc	T	A	7: 44,985,227 (GRCm39)	L126*	probably null	Het
Hspa8	T	G	9: 40,714,704 (GRCm39)	D333E	probably benign	Het
Igsf3	T	A	3: 101,338,895 (GRCm39)	V403D	probably benign	Het
Itga10	C	A	3: 96,555,475 (GRCm39)	A143D	probably damaging	Het
Kdr	T	A	5: 76,104,985 (GRCm39)	I1082F	probably damaging	Het
Klk1b11	A	T	7: 43,428,254 (GRCm39)	I242F	probably damaging	Het
Kng2	G	A	16: 22,806,522 (GRCm39)	T559I	probably benign	Het
Map1b	G	A	13: 99,570,163 (GRCm39)	P853S	unknown	Het
Mmp13	T	C	9: 7,280,880 (GRCm39)	I421T	possibly damaging	Het
Mpeg1	A	T	19: 12,439,615 (GRCm39)	T358S	probably damaging	Het
Msantd5l	A	C	11: 51,145,474 (GRCm39)	W38G	probably damaging	Het
Mttp	T	C	3: 137,800,783 (GRCm39)	D759G	probably damaging	Het
Mup17	T	A	4: 61,511,929 (GRCm39)	Y115F	possibly damaging	Het
Myo1a	G	T	10: 127,541,697 (GRCm39)	A79S	probably damaging	Het
Myo9a	T	A	9: 59,778,436 (GRCm39)	N1397K	probably benign	Het
Nadk2	T	C	15: 9,103,469 (GRCm39)		probably null	Het
Ncf1	A	T	5: 134,250,615 (GRCm39)	S402T	probably benign	Het
Ndufb10	T	C	17: 24,941,188 (GRCm39)	D145G	probably damaging	Het
Nlgn2	G	A	11: 69,721,409 (GRCm39)	T163M	possibly damaging	Het
Nol4	A	T	18: 22,903,801 (GRCm39)	H172Q		Het
Nup205	T	A	6: 35,202,904 (GRCm39)	D1370E	possibly damaging	Het
Or1e32	A	C	11: 73,705,112 (GRCm39)	N265K	probably damaging	Het
Or51ab3	T	A	7: 103,201,892 (GRCm39)	I300N	probably damaging	Het
Or5b97	A	G	19: 12,878,637 (GRCm39)	F169S	probably damaging	Het
Pkd1l2	A	G	8: 117,750,773 (GRCm39)	V1746A	probably benign	Het
Plin2	T	A	4: 86,586,628 (GRCm39)	I68F	probably benign	Het
Proc	A	T	18: 32,268,952 (GRCm39)	M11K	probably benign	Het
Rif1	T	C	2: 51,995,631 (GRCm39)	V950A	probably benign	Het
Rmc1	A	G	18: 12,317,972 (GRCm39)	K362E	probably benign	Het
Rnf208	C	A	2: 25,133,587 (GRCm39)	P94T	probably damaging	Het
Rundc3b	A	T	5: 8,571,011 (GRCm39)	Y269*	probably null	Het
Senp7	T	C	16: 56,006,445 (GRCm39)	V950A	probably benign	Het
Sipa1l1	T	C	12: 82,419,269 (GRCm39)	V649A	probably damaging	Het
Sipa1l3	G	T	7: 29,099,121 (GRCm39)	H383N	probably benign	Het
Slc7a7	A	G	14: 54,616,482 (GRCm39)	I200T	probably damaging	Het
Spdye4b	A	C	5: 143,188,103 (GRCm39)	I199L	probably damaging	Het
Styxl2	G	A	1: 165,926,300 (GRCm39)	T1104I	possibly damaging	Het
Tle4	A	T	19: 14,495,155 (GRCm39)	H191Q	probably benign	Het
Tnfsf13b	C	A	8: 10,081,651 (GRCm39)	S271*	probably null	Het
Tnks2	G	A	19: 36,856,839 (GRCm39)	V855I	probably benign	Het
Trank1	T	C	9: 111,196,194 (GRCm39)	L1406S	probably damaging	Het
Trhde	T	C	10: 114,636,478 (GRCm39)	E243G	probably damaging	Het
Trim25	A	T	11: 88,906,608 (GRCm39)	N448I	probably benign	Het
Trim31	T	A	17: 37,218,194 (GRCm39)	M308K	probably benign	Het
Ugt2b36	A	T	5: 87,214,138 (GRCm39)	V502E	possibly damaging	Het
Usp10	A	C	8: 120,668,344 (GRCm39)	D215A	possibly damaging	Het
Usp33	T	G	3: 152,066,026 (GRCm39)	L102*	probably null	Het
Wdr12	A	T	1: 60,121,734 (GRCm39)	C272*	probably null	Het
Xndc1	A	C	7: 101,727,938 (GRCm39)		probably null	Het
Zkscan2	T	C	7: 123,089,276 (GRCm39)	I332V	possibly damaging	Het
Zswim5	A	T	4: 116,841,885 (GRCm39)	T822S	probably benign	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
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'- TCTGAGGCTGGCCCTTATAGAC -3'
(R):5'- AAGCTGGCATGTGGTGTCAC -3'

Sequencing Primer
(F):5'- GAGGCTGGCCCTTATAGACATATAC -3'
(R):5'- TATGTGCTGAGACTCGCAC -3'

Posted On

2019-06-26