Mutagenetix > Incidental Mutation

Incidental Mutation 'R0276:Lrrc8a'

35347

Institutional Source

Beutler Lab

Gene Symbol

Lrrc8a

Ensembl Gene

ENSMUSG00000007476

Gene Name

leucine rich repeat containing 8A

Synonyms

Lrrc8

MMRRC Submission

038498-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0276 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

30237715-30263790 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 30256788 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 538 (D538G)

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: D538G

PolyPhen 2 Score 0.539 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000092690
Gene: ENSMUSG00000007476
AA Change: D538G

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: D538G

PolyPhen 2 Score 0.539 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000109284
Gene: ENSMUSG00000007476
AA Change: D538G

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: D538G

PolyPhen 2 Score 0.539 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000139038
Gene: ENSMUSG00000099041
AA Change: D538G

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

0.2787

Coding Region Coverage

1x: 98.7%
3x: 97.8%
10x: 96.2%
20x: 93.8%

Validation Efficiency

98% (101/103)

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: 100 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adamts13	A	G	2: 26,975,760 (GRCm38)	N109S	possibly damaging	Het
Adcy10	T	A	1: 165,572,591 (GRCm38)	M1523K	possibly damaging	Het
Agtpbp1	C	T	13: 59,462,031 (GRCm38)	S1095N	possibly damaging	Het
Ang2	C	T	14: 51,195,518 (GRCm38)	V136I	probably damaging	Het
Arhgap10	A	T	8: 77,413,581 (GRCm38)	M250K	probably benign	Het
Arhgap33	A	T	7: 30,523,244 (GRCm38)	W1088R	probably benign	Het
Arhgef15	T	C	11: 68,953,472 (GRCm38)		probably benign	Het
Aspm	T	C	1: 139,478,471 (GRCm38)	S1699P	possibly damaging	Het
Atp12a	C	A	14: 56,387,694 (GRCm38)	D1014E	probably damaging	Het
Atp1a4	T	A	1: 172,257,901 (GRCm38)	K45M	probably damaging	Het
Atp8a1	A	T	5: 67,786,673 (GRCm38)		probably benign	Het
Baiap3	A	C	17: 25,243,687 (GRCm38)	F1099C	probably damaging	Het
Bcas3	T	A	11: 85,470,837 (GRCm38)		probably null	Het
Bms1	G	A	6: 118,408,134 (GRCm38)	T371M	possibly damaging	Het
Camta1	C	A	4: 151,075,140 (GRCm38)	R1614L	probably damaging	Het
Capn3	T	C	2: 120,488,065 (GRCm38)		probably benign	Het
Ccdc180	A	G	4: 45,923,534 (GRCm38)	D1105G	probably damaging	Het
Ccdc33	G	T	9: 58,058,392 (GRCm38)	P364Q	probably damaging	Het
Ccdc36	A	T	9: 108,428,440 (GRCm38)	M11K	possibly damaging	Het
Clstn3	A	G	6: 124,431,740 (GRCm38)		probably benign	Het
Cntrl	A	T	2: 35,151,732 (GRCm38)	Y619F	possibly damaging	Het
Col12a1	A	T	9: 79,630,741 (GRCm38)	Y2514*	probably null	Het
Cpt1b	T	C	15: 89,419,959 (GRCm38)	H503R	probably benign	Het
Crb1	T	A	1: 139,323,335 (GRCm38)	T293S	possibly damaging	Het
D130043K22Rik	C	T	13: 24,858,045 (GRCm38)	T319I	possibly damaging	Het
Dzip1l	G	A	9: 99,660,998 (GRCm38)	R502Q	probably benign	Het
Efcab5	G	A	11: 77,140,923 (GRCm38)	R42W	probably damaging	Het
Efcab5	A	G	11: 77,129,876 (GRCm38)	M673T	probably damaging	Het
F2rl3	A	G	8: 72,762,798 (GRCm38)	T218A	probably benign	Het
Fam135a	C	T	1: 24,067,964 (GRCm38)	R31H	probably damaging	Het
Fam84b	G	T	15: 60,823,674 (GRCm38)	Y74*	probably null	Het
Fcer2a	A	T	8: 3,689,811 (GRCm38)	N53K	possibly damaging	Het
Gm14085	T	A	2: 122,521,928 (GRCm38)	S389T	probably damaging	Het
Golgb1	A	C	16: 36,913,876 (GRCm38)	K1162Q	probably damaging	Het
Gpr137b	A	T	13: 13,367,575 (GRCm38)		probably benign	Het
Haspin	A	T	11: 73,136,487 (GRCm38)	L592Q	probably damaging	Het
Helq	A	G	5: 100,790,147 (GRCm38)	F478L	probably damaging	Het
Il17rb	T	A	14: 30,004,380 (GRCm38)	T84S	probably damaging	Het
Itga4	T	C	2: 79,321,493 (GRCm38)	L880P	probably damaging	Het
Itih5	A	G	2: 10,185,564 (GRCm38)	I61V	possibly damaging	Het
Ivl	G	A	3: 92,571,514 (GRCm38)	L415F	unknown	Het
Kif2a	A	G	13: 106,976,650 (GRCm38)		probably benign	Het
Kmt2d	T	C	15: 98,850,311 (GRCm38)		probably benign	Het
Lars2	A	G	9: 123,438,121 (GRCm38)		probably benign	Het
Lilrb4a	T	C	10: 51,491,581 (GRCm38)	V73A	probably benign	Het
Lrrk1	G	A	7: 66,296,263 (GRCm38)		probably benign	Het
Mc2r	A	T	18: 68,408,132 (GRCm38)	I30K	possibly damaging	Het
Mybbp1a	C	A	11: 72,450,107 (GRCm38)		probably null	Het
Napg	C	T	18: 62,986,963 (GRCm38)	R149C	probably damaging	Het
Ncam2	A	G	16: 81,517,629 (GRCm38)		probably benign	Het
Nlk	T	C	11: 78,571,475 (GRCm38)	I509V	probably benign	Het
Nlrp2	A	T	7: 5,328,109 (GRCm38)	N429K	probably benign	Het
Nlrp9b	A	G	7: 20,028,498 (GRCm38)	T247A	probably benign	Het
Noxo1	A	T	17: 24,700,162 (GRCm38)		probably null	Het
Olfr1212	T	A	2: 88,958,755 (GRCm38)	C96*	probably null	Het
Olfr139	A	G	11: 74,045,118 (GRCm38)	I52T	probably damaging	Het
Olfr353	A	T	2: 36,890,023 (GRCm38)	M275K	probably benign	Het
Olfr701	A	T	7: 106,818,697 (GRCm38)	I205L	probably benign	Het
Olfr734	C	A	14: 50,320,179 (GRCm38)	A219S	probably benign	Het
Oxr1	T	C	15: 41,820,062 (GRCm38)	S294P	probably damaging	Het
Pfpl	A	G	19: 12,429,237 (GRCm38)	Y284C	probably damaging	Het
Pi16	A	T	17: 29,326,943 (GRCm38)	T232S	probably benign	Het
Plcxd2	A	T	16: 46,009,707 (GRCm38)	N50K	probably benign	Het
Plekhn1	T	A	4: 156,228,246 (GRCm38)	N52Y	probably damaging	Het
Prl2c5	T	C	13: 13,183,049 (GRCm38)		probably benign	Het
Prrc2b	G	A	2: 32,219,654 (GRCm38)	V1080I	probably damaging	Het
Psg28	A	T	7: 18,430,396 (GRCm38)	N130K	probably benign	Het
Psme4	C	A	11: 30,811,980 (GRCm38)	T440K	probably damaging	Het
Ptcd2	T	C	13: 99,321,596 (GRCm38)	K296E	probably benign	Het
Ptprq	T	C	10: 107,542,735 (GRCm38)		probably null	Het
Rab5b	A	C	10: 128,686,746 (GRCm38)		probably null	Het
Rft1	T	A	14: 30,690,583 (GRCm38)	S534T	probably benign	Het
Rif1	GCCACCA	GCCA	2: 52,110,324 (GRCm38)		probably benign	Het
Rsu1	A	T	2: 13,170,135 (GRCm38)		probably benign	Het
Senp6	A	G	9: 80,136,747 (GRCm38)	M887V	probably benign	Het
Sgcz	T	A	8: 37,952,919 (GRCm38)	M60L	probably benign	Het
Siglec1	G	A	2: 131,083,941 (GRCm38)	Q282*	probably null	Het
Sipa1l2	T	C	8: 125,421,940 (GRCm38)	T1655A	probably damaging	Het
Slc43a3	G	A	2: 84,937,663 (GRCm38)		probably benign	Het
Snx29	T	C	16: 11,738,373 (GRCm38)	V756A	probably benign	Het
Spta1	T	A	1: 174,217,894 (GRCm38)	H1539Q	probably damaging	Het
Stk3	A	C	15: 35,099,469 (GRCm38)	S104A	probably damaging	Het
Stk38	C	A	17: 28,992,416 (GRCm38)		probably null	Het
Stx6	T	C	1: 155,174,163 (GRCm38)		probably benign	Het
Thbs4	G	A	13: 92,775,532 (GRCm38)	T230I	probably benign	Het
Thrsp	A	G	7: 97,417,502 (GRCm38)	M1T	probably null	Het
Tmem63b	A	T	17: 45,675,373 (GRCm38)		probably benign	Het
Top2a	A	G	11: 99,009,907 (GRCm38)		probably benign	Het
Tpd52l2	T	C	2: 181,502,059 (GRCm38)		probably null	Het
Trak1	A	G	9: 121,454,338 (GRCm38)	E390G	probably damaging	Het
Trappc3	T	A	4: 126,273,952 (GRCm38)	D101E	possibly damaging	Het
Trhr	A	G	15: 44,197,086 (GRCm38)	M1V	probably null	Het
Triobp	T	A	15: 78,973,676 (GRCm38)	I1159K	probably benign	Het
Unc45a	A	G	7: 80,326,297 (GRCm38)		probably benign	Het
Usb1	A	G	8: 95,333,457 (GRCm38)	D12G	probably damaging	Het
Ushbp1	C	T	8: 71,394,649 (GRCm38)	C113Y	possibly damaging	Het
Vim	A	G	2: 13,574,859 (GRCm38)	K143R	probably benign	Het
Vmn2r75	T	C	7: 86,148,307 (GRCm38)	K766R	probably benign	Het
Wdr92	T	C	11: 17,229,821 (GRCm38)	I274T	probably benign	Het
Xpo5	T	G	17: 46,241,507 (GRCm38)	C1089G	probably damaging	Het

Other mutations in Lrrc8a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00693:Lrrc8a	APN	2	30,255,315 (GRCm38)	missense	probably benign	0.32
IGL01161:Lrrc8a	APN	2	30,255,810 (GRCm38)	missense	probably damaging	1.00
IGL01419:Lrrc8a	APN	2	30,257,099 (GRCm38)	missense	probably benign	0.09
IGL01757:Lrrc8a	APN	2	30,255,525 (GRCm38)	missense	possibly damaging	0.81
IGL02390:Lrrc8a	APN	2	30,256,701 (GRCm38)	missense	probably damaging	1.00
IGL02608:Lrrc8a	APN	2	30,256,299 (GRCm38)	missense	possibly damaging	0.91
IGL02938:Lrrc8a	APN	2	30,255,686 (GRCm38)	missense	probably damaging	1.00
IGL02960:Lrrc8a	APN	2	30,257,013 (GRCm38)	missense	probably damaging	1.00
IGL03139:Lrrc8a	APN	2	30,255,671 (GRCm38)	missense	probably damaging	1.00
IGL03166:Lrrc8a	APN	2	30,255,365 (GRCm38)	missense	probably benign
R0033:Lrrc8a	UTSW	2	30,255,345 (GRCm38)	missense	probably damaging	1.00
R0033:Lrrc8a	UTSW	2	30,255,345 (GRCm38)	missense	probably damaging	1.00
R0432:Lrrc8a	UTSW	2	30,257,067 (GRCm38)	missense	probably damaging	1.00
R0751:Lrrc8a	UTSW	2	30,256,350 (GRCm38)	missense	possibly damaging	0.82
R1924:Lrrc8a	UTSW	2	30,255,250 (GRCm38)	missense	probably damaging	1.00
R2029:Lrrc8a	UTSW	2	30,256,649 (GRCm38)	missense	probably damaging	1.00
R3852:Lrrc8a	UTSW	2	30,261,960 (GRCm38)	missense	probably benign	0.30
R4898:Lrrc8a	UTSW	2	30,257,202 (GRCm38)	missense	probably benign	0.00
R5175:Lrrc8a	UTSW	2	30,255,512 (GRCm38)	missense	probably damaging	1.00
R5616:Lrrc8a	UTSW	2	30,255,354 (GRCm38)	missense	probably benign	0.09
R5874:Lrrc8a	UTSW	2	30,257,136 (GRCm38)	missense	probably damaging	1.00
R6228:Lrrc8a	UTSW	2	30,256,553 (GRCm38)	missense	possibly damaging	0.82
R6406:Lrrc8a	UTSW	2	30,257,091 (GRCm38)	missense	possibly damaging	0.56
R6456:Lrrc8a	UTSW	2	30,255,474 (GRCm38)	missense	probably benign	0.14
R6833:Lrrc8a	UTSW	2	30,255,647 (GRCm38)	missense	possibly damaging	0.92
R6834:Lrrc8a	UTSW	2	30,255,647 (GRCm38)	missense	possibly damaging	0.92
R6945:Lrrc8a	UTSW	2	30,256,227 (GRCm38)	missense	probably damaging	1.00
R7675:Lrrc8a	UTSW	2	30,255,668 (GRCm38)	missense	probably damaging	1.00
R8500:Lrrc8a	UTSW	2	30,256,196 (GRCm38)	missense	possibly damaging	0.65
R8528:Lrrc8a	UTSW	2	30,255,545 (GRCm38)	missense	probably damaging	1.00
R8734:Lrrc8a	UTSW	2	30,256,607 (GRCm38)	missense	probably benign	0.12
R8879:Lrrc8a	UTSW	2	30,256,298 (GRCm38)	missense	probably benign	0.16
R9112:Lrrc8a	UTSW	2	30,255,770 (GRCm38)	missense	probably damaging	0.99
R9130:Lrrc8a	UTSW	2	30,257,030 (GRCm38)	missense	possibly damaging	0.82
R9456:Lrrc8a	UTSW	2	30,255,651 (GRCm38)	missense	probably damaging	1.00
Z1177:Lrrc8a	UTSW	2	30,256,313 (GRCm38)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- AGGTCCTGAAGCTGGAGCTGATAC -3'
(R):5'- CAGGTGCTGGAAGCTGATGATCTC -3'

Sequencing Primer
(F):5'- AGCTGATACCCGACGTGAC -3'
(R):5'- GGAAGCTGATGATCTCCTCAATG -3'

Posted On

2013-05-09