Mutagenetix > Incidental Mutation

Incidental Mutation 'R4750:Slc12a5'

357469

Institutional Source

Beutler Lab

Gene Symbol

Slc12a5

Ensembl Gene

ENSMUSG00000017740

Gene Name

solute carrier family 12, member 5

Synonyms

KCC2

MMRRC Submission

042031-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4750 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

164960802-164999731 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 164982931 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Valine at position 396 (M396V)

Ref Sequence

ENSEMBL: ENSMUSP00000096690 (fasta)

Gene Model

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

AlphaFold

Q91V14

Predicted Effect

probably benign
Transcript: ENSMUST00000099092
AA Change: M396V

PolyPhen 2 Score 0.065 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000096690
Gene: ENSMUSG00000017740
AA Change: M396V

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

noncoding transcript
Transcript: ENSMUST00000135918

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 benign
Transcript: ENSMUST00000202223
AA Change: M419V

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)

SMART Domains

Protein: ENSMUSP00000143870
Gene: ENSMUSG00000017740
AA Change: M419V

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: M419V

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)

SMART Domains

Protein: ENSMUSP00000144623
Gene: ENSMUSG00000017740
AA Change: M419V

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

Meta Mutation Damage Score

0.0843

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.2%
20x: 94.9%

Validation Efficiency

97% (89/92)

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: 83 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2510039O18Rik	T	A	4: 147,941,488 (GRCm38)	L155Q	probably damaging	Het
Aadac	T	C	3: 60,035,817 (GRCm38)	F48L	probably benign	Het
Aadat	T	A	8: 60,526,600 (GRCm38)	N165K	probably benign	Het
Acan	C	A	7: 79,092,718 (GRCm38)	D557E	probably damaging	Het
Adamts4	T	A	1: 171,251,066 (GRCm38)	V85D	probably benign	Het
Agt	A	G	8: 124,556,937 (GRCm38)	V481A	probably benign	Het
Angpt1	T	C	15: 42,676,401 (GRCm38)	N21D	probably benign	Het
Ankrd52	A	C	10: 128,378,089 (GRCm38)	D38A	probably damaging	Het
Ap1g2	G	T	14: 55,104,365 (GRCm38)	Q247K	probably damaging	Het
Apaf1	T	C	10: 91,060,188 (GRCm38)	R341G	probably damaging	Het
Arf2	T	C	11: 103,979,759 (GRCm38)		probably null	Het
Arhgef1	A	G	7: 24,918,576 (GRCm38)		probably benign	Het
Bbln	C	T	2: 32,379,413 (GRCm38)		probably null	Het
Bbox1	T	A	2: 110,265,521 (GRCm38)	Y366F	possibly damaging	Het
Bmp3	A	G	5: 98,872,558 (GRCm38)	E280G	possibly damaging	Het
Cd109	CATTTATTTATTTATTTATTTATTTATTTATTTAT	CATTTATTTATTTATTTATTTATTTATTTATTTATTTAT	9: 78,712,500 (GRCm38)		probably benign	Het
Cdh12	T	A	15: 21,583,808 (GRCm38)	V578D	possibly damaging	Het
Cdk19	T	C	10: 40,476,199 (GRCm38)	S282P	probably damaging	Het
Cfap46	A	G	7: 139,679,323 (GRCm38)		probably null	Het
Cfhr3	T	A	1: 139,584,828 (GRCm38)		noncoding transcript	Het
Ctrc	T	A	4: 141,841,523 (GRCm38)	Y123F	probably benign	Het
Dync2i2	T	C	2: 30,033,920 (GRCm38)	T198A	probably benign	Het
Enpp4	A	G	17: 44,102,355 (GRCm38)	M96T	probably damaging	Het
Exosc10	T	A	4: 148,562,394 (GRCm38)	S154T	possibly damaging	Het
Fbxo21	G	A	5: 118,000,468 (GRCm38)	R486H	probably benign	Het
Foxj3	C	A	4: 119,616,590 (GRCm38)	A204E	probably damaging	Het
Gas6	T	G	8: 13,476,227 (GRCm38)	D237A	probably benign	Het
Gimap8	A	G	6: 48,650,427 (GRCm38)	S112G	probably benign	Het
Gm4787	T	C	12: 81,378,367 (GRCm38)	N339S	possibly damaging	Het
Gm6185	T	C	1: 161,182,363 (GRCm38)		noncoding transcript	Het
Gramd2b	A	G	18: 56,432,300 (GRCm38)	E9G	probably benign	Het
Hmgxb3	A	T	18: 61,167,496 (GRCm38)	D169E	probably benign	Het
Isl2	T	A	9: 55,544,312 (GRCm38)	V162D	probably benign	Het
Kcns3	T	A	12: 11,091,654 (GRCm38)	D348V	probably damaging	Het
Kcp	G	A	6: 29,484,626 (GRCm38)	P1318S	probably benign	Het
Kif12	T	A	4: 63,167,783 (GRCm38)	Q415L	probably damaging	Het
Lama3	T	A	18: 12,504,359 (GRCm38)	H45Q	probably benign	Het
Lonp2	A	T	8: 86,631,502 (GRCm38)	K117M	probably benign	Het
Loxl4	T	A	19: 42,605,004 (GRCm38)	N243Y	probably damaging	Het
Lrif1	C	A	3: 106,735,564 (GRCm38)	Q662K	probably benign	Het
Lrrc37a	T	A	11: 103,455,480 (GRCm38)	I3187L	probably benign	Het
Lsg1	A	G	16: 30,565,449 (GRCm38)	I521T	probably damaging	Het
Mecom	T	G	3: 29,957,530 (GRCm38)	K865Q	probably damaging	Het
Myh10	T	C	11: 68,785,314 (GRCm38)	I790T	probably damaging	Het
Nek7	C	T	1: 138,498,673 (GRCm38)	S234N	probably damaging	Het
Nepro	T	C	16: 44,730,182 (GRCm38)	L179P	probably damaging	Het
Nexn	A	G	3: 152,237,722 (GRCm38)	C649R	probably damaging	Het
Nsmf	T	C	2: 25,055,026 (GRCm38)	S34P	probably damaging	Het
Or10x1	A	G	1: 174,368,922 (GRCm38)	I2V	probably benign	Het
Or13n4	A	G	7: 106,824,307 (GRCm38)	F73S	probably damaging	Het
Or13p5	T	A	4: 118,734,733 (GRCm38)	V68D	possibly damaging	Het
Or1n2	T	A	2: 36,907,716 (GRCm38)	S257T	probably benign	Het
Or1p1c	T	A	11: 74,269,420 (GRCm38)	F10L	probably benign	Het
Or2w2	A	G	13: 21,573,743 (GRCm38)	S238P	possibly damaging	Het
Or52l1	A	T	7: 105,180,926 (GRCm38)	I144N	probably damaging	Het
Or5bw2	A	G	7: 6,570,851 (GRCm38)	I287V	probably benign	Het
Or5w16	C	T	2: 87,746,508 (GRCm38)	T104I	probably benign	Het
P2rx5	G	T	11: 73,164,877 (GRCm38)	K53N	probably damaging	Het
Pcdhb20	C	A	18: 37,506,131 (GRCm38)	A570E	possibly damaging	Het
Pip4k2c	T	C	10: 127,211,417 (GRCm38)	H32R	unknown	Het
Pkhd1	T	A	1: 20,524,112 (GRCm38)	D1259V	possibly damaging	Het
Plekha7	A	T	7: 116,137,311 (GRCm38)	V889E	probably damaging	Het
Polr2b	A	C	5: 77,332,039 (GRCm38)	E546D	possibly damaging	Het
Ppm1l	A	G	3: 69,549,328 (GRCm38)	T193A	probably damaging	Het
Ppp1r37	G	T	7: 19,531,520 (GRCm38)	D710E	probably benign	Het
Prdm4	A	G	10: 85,899,221 (GRCm38)	F679L	probably damaging	Het
Prkcd	A	G	14: 30,610,301 (GRCm38)	M1T	probably null	Het
Prss59	A	G	6: 40,921,021 (GRCm38)	W243R	probably damaging	Het
Rcor3	A	G	1: 192,130,449 (GRCm38)	Y77H	unknown	Het
Rdh5	T	C	10: 128,918,366 (GRCm38)	E66G	possibly damaging	Het
Slco5a1	T	G	1: 12,879,280 (GRCm38)	T629P	probably damaging	Het
Smarca5	A	C	8: 80,733,707 (GRCm38)	N133K	probably benign	Het
Spag5	T	C	11: 78,320,052 (GRCm38)	M927T	probably benign	Het
Spint4	A	T	2: 164,700,146 (GRCm38)	D39V	probably damaging	Het
Syt6	T	A	3: 103,630,917 (GRCm38)	*512R	probably null	Het
Tmem247	T	C	17: 86,922,342 (GRCm38)	C204R	probably damaging	Het
Tmem72	A	G	6: 116,695,434 (GRCm38)	Y149H	probably damaging	Het
Trpm6	T	C	19: 18,876,064 (GRCm38)	V1816A	probably damaging	Het
Usp35	A	G	7: 97,310,339 (GRCm38)	V1008A	possibly damaging	Het
Washc4	T	C	10: 83,591,052 (GRCm38)	S1075P	probably damaging	Het
Xylb	G	T	9: 119,359,313 (GRCm38)	G62*	probably null	Het
Zfp142	T	C	1: 74,572,458 (GRCm38)	E623G	probably damaging	Het
Zfp239	A	G	6: 117,871,739 (GRCm38)	Y146C	probably damaging	Het

Other mutations in Slc12a5

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00324:Slc12a5	APN	2	164,997,121 (GRCm38)	missense	probably damaging	1.00
IGL00425:Slc12a5	APN	2	164,983,281 (GRCm38)	missense	probably damaging	1.00
IGL00976:Slc12a5	APN	2	164,979,304 (GRCm38)	missense	probably damaging	1.00
IGL01654:Slc12a5	APN	2	164,973,755 (GRCm38)	missense	possibly damaging	0.91
IGL01905:Slc12a5	APN	2	164,990,381 (GRCm38)	missense	probably benign	0.02
IGL02205:Slc12a5	APN	2	164,996,479 (GRCm38)	missense	probably benign	0.03
IGL02510:Slc12a5	APN	2	164,982,808 (GRCm38)	splice site	probably benign
IGL02746:Slc12a5	APN	2	164,974,916 (GRCm38)	missense	probably benign	0.01
G1Funyon:Slc12a5	UTSW	2	164,993,691 (GRCm38)	missense	probably damaging	0.98
R0051:Slc12a5	UTSW	2	164,986,663 (GRCm38)	missense	probably damaging	1.00
R0254:Slc12a5	UTSW	2	164,997,245 (GRCm38)	critical splice donor site	probably null
R0412:Slc12a5	UTSW	2	164,994,062 (GRCm38)	missense	probably benign	0.05
R0587:Slc12a5	UTSW	2	164,976,533 (GRCm38)	missense	probably damaging	1.00
R0835:Slc12a5	UTSW	2	164,994,038 (GRCm38)	missense	probably damaging	0.97
R0932:Slc12a5	UTSW	2	164,996,885 (GRCm38)	splice site	probably benign
R1643:Slc12a5	UTSW	2	164,994,027 (GRCm38)	missense	probably benign	0.01
R1700:Slc12a5	UTSW	2	164,992,376 (GRCm38)	missense	possibly damaging	0.94
R1760:Slc12a5	UTSW	2	164,996,128 (GRCm38)	missense	probably damaging	0.99
R2063:Slc12a5	UTSW	2	164,997,147 (GRCm38)	missense	probably damaging	1.00
R2293:Slc12a5	UTSW	2	164,992,330 (GRCm38)	missense	probably benign	0.03
R2412:Slc12a5	UTSW	2	164,976,462 (GRCm38)	critical splice donor site	probably null
R3035:Slc12a5	UTSW	2	164,980,258 (GRCm38)	missense	probably benign	0.06
R3116:Slc12a5	UTSW	2	164,996,181 (GRCm38)	splice site	probably null
R3412:Slc12a5	UTSW	2	164,968,431 (GRCm38)	missense	probably benign	0.26
R3788:Slc12a5	UTSW	2	164,993,775 (GRCm38)	missense	probably damaging	1.00
R4039:Slc12a5	UTSW	2	164,992,330 (GRCm38)	missense	probably benign	0.03
R4174:Slc12a5	UTSW	2	164,979,490 (GRCm38)	missense	probably damaging	1.00
R4492:Slc12a5	UTSW	2	164,979,343 (GRCm38)	missense	probably benign	0.08
R4608:Slc12a5	UTSW	2	164,973,765 (GRCm38)	missense	probably damaging	0.99
R4994:Slc12a5	UTSW	2	164,983,365 (GRCm38)	splice site	probably null
R5103:Slc12a5	UTSW	2	164,992,433 (GRCm38)	missense	probably damaging	1.00
R5539:Slc12a5	UTSW	2	164,987,206 (GRCm38)	missense	possibly damaging	0.94
R5632:Slc12a5	UTSW	2	164,987,221 (GRCm38)	missense	possibly damaging	0.86
R5771:Slc12a5	UTSW	2	164,973,768 (GRCm38)	missense	possibly damaging	0.88
R6139:Slc12a5	UTSW	2	164,992,311 (GRCm38)	missense	probably damaging	0.98
R6336:Slc12a5	UTSW	2	164,992,464 (GRCm38)	splice site	probably null
R6581:Slc12a5	UTSW	2	164,987,115 (GRCm38)	missense	probably damaging	1.00
R6706:Slc12a5	UTSW	2	164,988,589 (GRCm38)	missense	probably damaging	1.00
R6886:Slc12a5	UTSW	2	164,982,905 (GRCm38)	missense	probably benign
R7134:Slc12a5	UTSW	2	164,974,958 (GRCm38)	missense	probably damaging	1.00
R7310:Slc12a5	UTSW	2	164,992,440 (GRCm38)	missense	probably damaging	1.00
R7402:Slc12a5	UTSW	2	164,982,932 (GRCm38)	missense	probably benign	0.01
R8079:Slc12a5	UTSW	2	164,992,452 (GRCm38)	missense	probably damaging	1.00
R8301:Slc12a5	UTSW	2	164,993,691 (GRCm38)	missense	probably damaging	0.98
R9105:Slc12a5	UTSW	2	164,996,194 (GRCm38)	missense	probably benign
R9132:Slc12a5	UTSW	2	164,993,956 (GRCm38)	intron	probably benign
R9431:Slc12a5	UTSW	2	164,990,258 (GRCm38)	missense	possibly damaging	0.95
R9580:Slc12a5	UTSW	2	164,974,976 (GRCm38)	missense	probably damaging	0.99
R9677:Slc12a5	UTSW	2	164,992,326 (GRCm38)	missense	possibly damaging	0.66

Predicted Primers

PCR Primer
(F):5'- TCATGCCCTGGTACAAAGCAG -3'
(R):5'- AACAACCAGTTCCGGCTTAGG -3'

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

Posted On

2015-11-11