Mutagenetix > Incidental Mutation

Incidental Mutation 'R5874:Lrrc8a'

455361

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

044081-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5874 (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 30147148 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Threonine at position 654 (I654T)

Ref Sequence

ENSEMBL: ENSMUSP00000139038 (fasta)

Gene Model

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

AlphaFold

Q80WG5

Predicted Effect

probably damaging
Transcript: ENSMUST00000095078
AA Change: I654T

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000092690
Gene: ENSMUSG00000007476
AA Change: I654T

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

probably damaging
Transcript: ENSMUST00000113654
AA Change: I654T

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000109284
Gene: ENSMUSG00000007476
AA Change: I654T

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

probably damaging
Transcript: ENSMUST00000139454
AA Change: I654T

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000139038
Gene: ENSMUSG00000099041
AA Change: I654T

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

0.7979

Coding Region Coverage

1x: 99.9%
3x: 99.5%
10x: 97.8%
20x: 93.6%

Validation Efficiency

98% (86/88)

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: 73 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930432E11Rik	G	A	7: 29,280,610 (GRCm39)		noncoding transcript	Het
Adam17	T	C	12: 21,379,087 (GRCm39)	D654G	possibly damaging	Het
Ankhd1	A	T	18: 36,773,322 (GRCm39)	H1373L	possibly damaging	Het
Ankrd17	T	C	5: 90,416,656 (GRCm39)		probably benign	Het
Calu	A	G	6: 29,372,617 (GRCm39)	D112G	probably damaging	Het
Camk2a	G	C	18: 61,076,272 (GRCm39)		probably benign	Het
Cpn1	C	A	19: 43,944,951 (GRCm39)	R452L	probably benign	Het
Csmd3	T	A	15: 47,507,666 (GRCm39)	E2780V	probably damaging	Het
Ctnna2	T	C	6: 76,879,413 (GRCm39)	T824A	probably benign	Het
Cuedc2	C	T	19: 46,319,824 (GRCm39)	V164M	possibly damaging	Het
Cyp2d34	T	A	15: 82,503,243 (GRCm39)	D74V	probably benign	Het
Ddi2	A	G	4: 141,422,780 (GRCm39)	S311P	probably damaging	Het
Ddx10	A	C	9: 53,140,498 (GRCm39)	I301R	possibly damaging	Het
Dmpk	T	C	7: 18,826,007 (GRCm39)		probably benign	Het
Dnah7b	C	T	1: 46,230,885 (GRCm39)	T1381I	probably damaging	Het
Dst	T	A	1: 34,218,670 (GRCm39)	N1703K	probably damaging	Het
Dtwd1	T	A	2: 126,000,359 (GRCm39)	H98Q	probably damaging	Het
Ecel1	A	C	1: 87,075,731 (GRCm39)	V769G	probably benign	Het
Eno4	T	C	19: 58,935,238 (GRCm39)	V150A	probably benign	Het
Evc2	C	T	5: 37,574,883 (GRCm39)		probably benign	Het
Ext1	T	A	15: 52,965,148 (GRCm39)	Q406L	possibly damaging	Het
Foxf2	A	G	13: 31,810,775 (GRCm39)	H238R	probably benign	Het
Frem2	C	G	3: 53,444,910 (GRCm39)	G2407A	probably benign	Het
Fzd10	A	G	5: 128,678,364 (GRCm39)	E28G	probably benign	Het
Galnt15	T	C	14: 31,774,324 (GRCm39)	F363L	probably damaging	Het
Gm1758	C	T	16: 14,325,037 (GRCm39)		noncoding transcript	Het
Gm5866	C	T	5: 52,739,956 (GRCm39)		noncoding transcript	Het
Heatr9	T	A	11: 83,405,426 (GRCm39)	M345L	probably benign	Het
Il23r	A	T	6: 67,408,629 (GRCm39)	F404Y	possibly damaging	Het
Napg	A	T	18: 63,111,091 (GRCm39)	K18*	probably null	Het
Ndst3	A	T	3: 123,355,556 (GRCm39)	W573R	probably damaging	Het
Nin	T	C	12: 70,077,692 (GRCm39)	S1038G	possibly damaging	Het
Nudt12	T	A	17: 59,317,279 (GRCm39)	R123*	probably null	Het
Oas1g	T	A	5: 121,015,081 (GRCm39)	N361Y	probably benign	Het
Or5p51	T	A	7: 107,444,377 (GRCm39)	I188L	probably benign	Het
Or7a35	T	A	10: 78,853,191 (GRCm39)	F12I	possibly damaging	Het
Or8h10	A	T	2: 86,808,786 (GRCm39)	M118K	probably damaging	Het
Osbpl10	T	C	9: 115,055,828 (GRCm39)	F667L	probably damaging	Het
Phldb2	T	C	16: 45,621,988 (GRCm39)	D664G	probably damaging	Het
Piezo2	C	T	18: 63,160,972 (GRCm39)	V2263M	probably damaging	Het
Pkd1l1	A	G	11: 8,858,688 (GRCm39)	L615P	probably damaging	Het
Pnpla7	G	A	2: 24,901,661 (GRCm39)	M562I	probably benign	Het
Pou2af2	A	T	9: 51,201,672 (GRCm39)	L128*	probably null	Het
Ppp1r13b	C	A	12: 111,811,423 (GRCm39)	R155L	probably damaging	Het
Pygb	C	T	2: 150,628,798 (GRCm39)	P4L	probably benign	Het
Rbm44	T	C	1: 91,084,562 (GRCm39)		probably null	Het
Rilpl2	T	C	5: 124,607,876 (GRCm39)	T115A	probably benign	Het
Rin3	A	G	12: 102,356,102 (GRCm39)	Y801C	probably damaging	Het
Rnf112	A	G	11: 61,340,273 (GRCm39)	V619A	probably damaging	Het
Rnf182	A	G	13: 43,821,563 (GRCm39)	E38G	probably benign	Het
Scgb2b24	T	A	7: 33,436,830 (GRCm39)	Y94F	probably damaging	Het
Serac1	C	A	17: 6,094,188 (GRCm39)		probably benign	Het
Shld2	T	C	14: 33,967,215 (GRCm39)	T114A	probably benign	Het
Slc6a19	A	T	13: 73,832,487 (GRCm39)	V402D	probably damaging	Het
Slco1a8	A	T	6: 141,917,961 (GRCm39)	H638Q	probably benign	Het
Slco2b1	T	A	7: 99,316,301 (GRCm39)	M410L	probably benign	Het
Smarca2	T	C	19: 26,753,469 (GRCm39)		probably benign	Het
Sned1	A	G	1: 93,193,067 (GRCm39)	Y409C	probably damaging	Het
Sorcs2	A	G	5: 36,386,555 (GRCm39)	V161A	probably damaging	Het
Spring1	T	C	5: 118,397,504 (GRCm39)	V162A	probably damaging	Het
Sptb	T	C	12: 76,645,501 (GRCm39)	E2029G	possibly damaging	Het
Stx7	T	A	10: 24,058,659 (GRCm39)		probably null	Het
Taf4b	T	C	18: 14,937,611 (GRCm39)	V228A	probably benign	Het
Tbc1d1	A	G	5: 64,507,273 (GRCm39)	*1163W	probably null	Het
Tor4a	G	A	2: 25,084,847 (GRCm39)	A352V	probably damaging	Het
Trpm4	A	G	7: 44,977,173 (GRCm39)	F81S	probably damaging	Het
Ttn	T	A	2: 76,780,436 (GRCm39)	D1105V	probably damaging	Het
Vcf1	T	A	11: 113,568,220 (GRCm39)	R78S	probably damaging	Het
Yju2b	T	A	8: 84,985,177 (GRCm39)	D364V	possibly damaging	Het
Zfp551	A	G	7: 12,150,101 (GRCm39)	L436P	probably damaging	Het
Zfp975	G	T	7: 42,312,312 (GRCm39)	D100E	probably benign	Het
Zswim3	A	G	2: 164,662,032 (GRCm39)	I171V	probably benign	Het
Zwint	C	T	10: 72,492,294 (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
R0751:Lrrc8a	UTSW	2	30,146,362 (GRCm39)	missense	possibly damaging	0.82
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
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'- TCAAGAAGATGGTTAACCTGACGG -3'
(R):5'- CTCACCCTATTGGCTGTGAC -3'

Sequencing Primer
(F):5'- TTAACCTGACGGAGCTAGAGC -3'
(R):5'- CTGTGACGGCCAGGTTCTG -3'

Posted On

2017-02-10