Mutagenetix > Incidental Mutation

Incidental Mutation 'R0751:Lrrc8a'

70302

Institutional Source

Beutler Lab

Gene Symbol

Lrrc8a

Ensembl Gene

ENSMUSG00000007476

Gene Name

leucine rich repeat containing 8A VRAC subunit A

Synonyms

ebo, Lrrc8, SWELL1

MMRRC Submission

038931-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0751 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

30127781-30153802 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 30146362 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 392 (V392A)

Ref Sequence

ENSEMBL: ENSMUSP00000139038 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000095078] [ENSMUST00000113654] [ENSMUST00000139454]

AlphaFold

Q80WG5

Predicted Effect

possibly damaging
Transcript: ENSMUST00000095078
AA Change: V392A

PolyPhen 2 Score 0.820 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000092690
Gene: ENSMUSG00000007476
AA Change: V392A

Domain	Start	End	E-Value	Type
Pfam:Pannexin_like	1	340	1.4e-146	PFAM
low complexity region	445	455	N/A	INTRINSIC
internal_repeat_1	461	526	7.6e-5	PROSPERO
low complexity region	540	558	N/A	INTRINSIC
LRR	590	613	5.41e0	SMART
LRR	614	636	3.18e2	SMART
LRR	638	660	6.78e1	SMART
LRR_TYP	661	684	1.06e-4	SMART
LRR	685	706	1.15e1	SMART
LRR_TYP	707	730	1.92e-2	SMART
LRR	731	751	1.81e2	SMART
LRR	753	776	2.02e-1	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000113654
AA Change: V392A

PolyPhen 2 Score 0.820 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000109284
Gene: ENSMUSG00000007476
AA Change: V392A

Domain	Start	End	E-Value	Type
Pfam:DUF3733	1	65	3.3e-32	PFAM
Pfam:DUF3733	97	156	2e-22	PFAM
transmembrane domain	320	342	N/A	INTRINSIC
low complexity region	445	455	N/A	INTRINSIC
internal_repeat_1	461	526	7.6e-5	PROSPERO
low complexity region	540	558	N/A	INTRINSIC
LRR	590	613	5.41e0	SMART
LRR	614	636	3.18e2	SMART
LRR	638	660	6.78e1	SMART
LRR_TYP	661	684	1.06e-4	SMART
LRR	685	706	1.15e1	SMART
LRR_TYP	707	730	1.92e-2	SMART
LRR	731	751	1.81e2	SMART
LRR	753	776	2.02e-1	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000139454
AA Change: V392A

PolyPhen 2 Score 0.820 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000139038
Gene: ENSMUSG00000099041
AA Change: V392A

Domain	Start	End	E-Value	Type
Pfam:DUF3733	1	65	3.3e-32	PFAM
Pfam:DUF3733	97	156	2e-22	PFAM
transmembrane domain	320	342	N/A	INTRINSIC
low complexity region	445	455	N/A	INTRINSIC
internal_repeat_1	461	526	7.6e-5	PROSPERO
low complexity region	540	558	N/A	INTRINSIC
LRR	590	613	5.41e0	SMART
LRR	614	636	3.18e2	SMART
LRR	638	660	6.78e1	SMART
LRR_TYP	661	684	1.06e-4	SMART
LRR	685	706	1.15e1	SMART
LRR_TYP	707	730	1.92e-2	SMART
LRR	731	751	1.81e2	SMART
LRR	753	776	2.02e-1	SMART

Meta Mutation Damage Score

0.2081

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.2%
20x: 94.4%

Validation Efficiency

99% (73/74)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein belonging to the leucine-rich repeat family of proteins, which are involved in diverse biological processes, including cell adhesion, cellular trafficking, and hormone-receptor interactions. This family member is a putative four-pass transmembrane protein that plays a role in B cell development. Defects in this gene cause autosomal dominant non-Bruton type agammaglobulinemia, an immunodeficiency disease resulting from defects in B cell maturation. Multiple alternatively spliced transcript variants, which encode the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous for a knock-out allele exhibit prenatal lethality and premature death, growth retardation, sterility, multiple tissue abnormalities, a severe block in early thymic development, and impaired peripheral T cell function. B cell development is modestly impaired but B cell function is normal. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 75 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Ahdc1	T	A	4: 132,792,707 (GRCm39)	M1316K	probably benign	Het
Alox12	T	C	11: 70,137,776 (GRCm39)	I455V	probably benign	Het
Ankrd28	A	G	14: 31,486,225 (GRCm39)	L89P	probably damaging	Het
Aqp9	A	T	9: 71,045,487 (GRCm39)	C41S	probably damaging	Het
Arhgap17	T	C	7: 122,913,913 (GRCm39)	Y199C	probably damaging	Het
Aspm	A	T	1: 139,384,636 (GRCm39)		probably benign	Het
Cacfd1	T	C	2: 26,908,993 (GRCm39)		probably null	Het
Cd33	T	C	7: 43,181,545 (GRCm39)	D205G	probably damaging	Het
Chadl	T	C	15: 81,577,258 (GRCm39)	S198G	probably benign	Het
Chtf8	A	G	8: 107,613,109 (GRCm39)		probably null	Het
Clec4a4	G	T	6: 122,989,671 (GRCm39)	W104L	probably benign	Het
Clock	A	T	5: 76,377,208 (GRCm39)	I696K	possibly damaging	Het
Crtc2	T	A	3: 90,169,940 (GRCm39)	Y445*	probably null	Het
Dapk1	A	T	13: 60,844,112 (GRCm39)	I44F	probably damaging	Het
Dcbld2	T	A	16: 58,270,204 (GRCm39)		probably null	Het
Derl2	T	C	11: 70,905,373 (GRCm39)		probably null	Het
Dnah7c	A	G	1: 46,505,065 (GRCm39)	T154A	probably benign	Het
Dnmt3b	T	A	2: 153,516,762 (GRCm39)		probably null	Het
Dusp3	A	T	11: 101,872,554 (GRCm39)	S106T	probably benign	Het
Eftud2	A	G	11: 102,730,079 (GRCm39)	V897A	probably damaging	Het
Eif3l	T	A	15: 78,959,966 (GRCm39)		probably null	Het
Fbxo33	A	C	12: 59,265,878 (GRCm39)	F130V	probably damaging	Het
Ffar3	T	A	7: 30,554,529 (GRCm39)	N264Y	probably damaging	Het
Fig4	T	C	10: 41,148,978 (GRCm39)	D158G	probably damaging	Het
Fyco1	A	G	9: 123,648,218 (GRCm39)	F1239L	probably damaging	Het
Gabra2	A	G	5: 71,249,442 (GRCm39)		probably benign	Het
Gabra6	C	A	11: 42,205,844 (GRCm39)	R336S	probably benign	Het
Hkdc1	T	C	10: 62,234,452 (GRCm39)	D581G	probably damaging	Het
Ift70a2	C	T	2: 75,808,375 (GRCm39)	A46T	probably damaging	Het
Iqgap1	A	G	7: 80,375,321 (GRCm39)		probably benign	Het
Larp4b	T	C	13: 9,216,345 (GRCm39)		probably benign	Het
Lcp1	A	T	14: 75,436,827 (GRCm39)	M58L	probably benign	Het
Mavs	A	T	2: 131,088,684 (GRCm39)	Y496F	probably damaging	Het
Mpi	A	T	9: 57,457,897 (GRCm39)	S102T	probably damaging	Het
Mroh9	G	A	1: 162,893,693 (GRCm39)	R161W	possibly damaging	Het
Myo1h	A	T	5: 114,458,747 (GRCm39)	S161C	probably damaging	Het
Napg	T	G	18: 63,127,409 (GRCm39)	H204Q	probably benign	Het
Nelfcd	C	A	2: 174,264,807 (GRCm39)	A182D	probably benign	Het
Ntsr2	G	T	12: 16,704,031 (GRCm39)	K91N	probably damaging	Het
Obscn	A	G	11: 58,972,645 (GRCm39)	S2134P	probably damaging	Het
Ogfod2	G	A	5: 124,251,539 (GRCm39)		probably benign	Het
Or13a19	G	A	7: 139,903,238 (GRCm39)	V209I	probably benign	Het
Or1e26	G	T	11: 73,479,970 (GRCm39)	T198K	probably benign	Het
Pcdha8	T	C	18: 37,127,123 (GRCm39)	V535A	probably damaging	Het
Pdlim2	C	T	14: 70,402,228 (GRCm39)	R296H	probably damaging	Het
Pik3r1	T	C	13: 101,822,866 (GRCm39)		probably null	Het
Pimreg	C	A	11: 71,933,939 (GRCm39)	Q22K	probably benign	Het
Pld5	A	G	1: 175,872,462 (GRCm39)	I225T	probably damaging	Het
Plxnc1	T	C	10: 94,667,195 (GRCm39)		probably benign	Het
Ppip5k2	A	T	1: 97,677,377 (GRCm39)	C306*	probably null	Het
Ptprc	A	G	1: 138,020,668 (GRCm39)	Y588H	probably damaging	Het
Rac2	T	G	15: 78,450,145 (GRCm39)	D65A	possibly damaging	Het
Rgl3	A	G	9: 21,888,676 (GRCm39)		probably null	Het
Serpinb1a	T	C	13: 33,027,199 (GRCm39)	K248E	probably benign	Het
Serpinb9e	A	C	13: 33,443,757 (GRCm39)	E259A	probably benign	Het
Slc12a4	A	T	8: 106,678,532 (GRCm39)	V266E	probably damaging	Het
Slc8b1	A	G	5: 120,662,260 (GRCm39)		probably benign	Het
Spink6	T	C	18: 44,204,605 (GRCm39)		probably benign	Het
Spta1	G	A	1: 174,012,256 (GRCm39)	R354H	probably damaging	Het
Ssb	T	A	2: 69,700,909 (GRCm39)	S330T	probably benign	Het
Stard9	G	T	2: 120,527,966 (GRCm39)	V1408F	probably benign	Het
Sumf2	A	T	5: 129,878,846 (GRCm39)	T61S	probably benign	Het
Sypl2	T	C	3: 108,124,072 (GRCm39)	T157A	probably damaging	Het
Tgfbr3	A	T	5: 107,287,749 (GRCm39)	D483E	probably damaging	Het
Tnrc6a	A	G	7: 122,769,563 (GRCm39)	N451S	possibly damaging	Het
Tradd	T	C	8: 105,986,403 (GRCm39)	E123G	probably damaging	Het
Trim36	T	C	18: 46,329,318 (GRCm39)	T41A	probably damaging	Het
Ttll7	C	T	3: 146,645,746 (GRCm39)	P535S	probably damaging	Het
Ubr4	C	T	4: 139,164,509 (GRCm39)		probably benign	Het
Uqcc5	G	T	14: 30,810,953 (GRCm39)		probably benign	Het
Vmn1r195	A	G	13: 22,463,181 (GRCm39)	Y217C	probably damaging	Het
Vmn2r63	A	C	7: 42,577,459 (GRCm39)	F360V	probably damaging	Het
Vmn2r78	G	A	7: 86,603,588 (GRCm39)	V589M	possibly damaging	Het
Vmn2r-ps158	A	G	7: 42,696,833 (GRCm39)	Y630C	probably damaging	Het
Vrk2	A	G	11: 26,433,331 (GRCm39)		probably benign	Het

Other mutations in Lrrc8a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00693:Lrrc8a	APN	2	30,145,327 (GRCm39)	missense	probably benign	0.32
IGL01161:Lrrc8a	APN	2	30,145,822 (GRCm39)	missense	probably damaging	1.00
IGL01419:Lrrc8a	APN	2	30,147,111 (GRCm39)	missense	probably benign	0.09
IGL01757:Lrrc8a	APN	2	30,145,537 (GRCm39)	missense	possibly damaging	0.81
IGL02390:Lrrc8a	APN	2	30,146,713 (GRCm39)	missense	probably damaging	1.00
IGL02608:Lrrc8a	APN	2	30,146,311 (GRCm39)	missense	possibly damaging	0.91
IGL02938:Lrrc8a	APN	2	30,145,698 (GRCm39)	missense	probably damaging	1.00
IGL02960:Lrrc8a	APN	2	30,147,025 (GRCm39)	missense	probably damaging	1.00
IGL03139:Lrrc8a	APN	2	30,145,683 (GRCm39)	missense	probably damaging	1.00
IGL03166:Lrrc8a	APN	2	30,145,377 (GRCm39)	missense	probably benign
R0033:Lrrc8a	UTSW	2	30,145,357 (GRCm39)	missense	probably damaging	1.00
R0033:Lrrc8a	UTSW	2	30,145,357 (GRCm39)	missense	probably damaging	1.00
R0276:Lrrc8a	UTSW	2	30,146,800 (GRCm39)	missense	possibly damaging	0.54
R0432:Lrrc8a	UTSW	2	30,147,079 (GRCm39)	missense	probably damaging	1.00
R1924:Lrrc8a	UTSW	2	30,145,262 (GRCm39)	missense	probably damaging	1.00
R2029:Lrrc8a	UTSW	2	30,146,661 (GRCm39)	missense	probably damaging	1.00
R3852:Lrrc8a	UTSW	2	30,151,972 (GRCm39)	missense	probably benign	0.30
R4898:Lrrc8a	UTSW	2	30,147,214 (GRCm39)	missense	probably benign	0.00
R5175:Lrrc8a	UTSW	2	30,145,524 (GRCm39)	missense	probably damaging	1.00
R5616:Lrrc8a	UTSW	2	30,145,366 (GRCm39)	missense	probably benign	0.09
R5874:Lrrc8a	UTSW	2	30,147,148 (GRCm39)	missense	probably damaging	1.00
R6228:Lrrc8a	UTSW	2	30,146,565 (GRCm39)	missense	possibly damaging	0.82
R6406:Lrrc8a	UTSW	2	30,147,103 (GRCm39)	missense	possibly damaging	0.56
R6456:Lrrc8a	UTSW	2	30,145,486 (GRCm39)	missense	probably benign	0.14
R6833:Lrrc8a	UTSW	2	30,145,659 (GRCm39)	missense	possibly damaging	0.92
R6834:Lrrc8a	UTSW	2	30,145,659 (GRCm39)	missense	possibly damaging	0.92
R6945:Lrrc8a	UTSW	2	30,146,239 (GRCm39)	missense	probably damaging	1.00
R7675:Lrrc8a	UTSW	2	30,145,680 (GRCm39)	missense	probably damaging	1.00
R8500:Lrrc8a	UTSW	2	30,146,208 (GRCm39)	missense	possibly damaging	0.65
R8528:Lrrc8a	UTSW	2	30,145,557 (GRCm39)	missense	probably damaging	1.00
R8734:Lrrc8a	UTSW	2	30,146,619 (GRCm39)	missense	probably benign	0.12
R8879:Lrrc8a	UTSW	2	30,146,310 (GRCm39)	missense	probably benign	0.16
R9112:Lrrc8a	UTSW	2	30,145,782 (GRCm39)	missense	probably damaging	0.99
R9130:Lrrc8a	UTSW	2	30,147,042 (GRCm39)	missense	possibly damaging	0.82
R9456:Lrrc8a	UTSW	2	30,145,663 (GRCm39)	missense	probably damaging	1.00
Z1177:Lrrc8a	UTSW	2	30,146,325 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- ATCAAGTTCGACGTGGACTGCACC -3'
(R):5'- TATCAGCTCCAGCTTCAGGACCTC -3'

Sequencing Primer
(F):5'- TGGACATCGAGAGCCTGAC -3'
(R):5'- TCAAACACAGTGTCCGGGATG -3'

Posted On

2013-09-30