Incidental Mutation 'R5175:Lrrc8a'
ID 399094
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 042755-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R5175 (G1)
Quality Score 225
Status Not validated
Chromosome 2
Chromosomal Location 30127781-30153802 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 30145524 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Cysteine to Arginine at position 113 (C113R)
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: C113R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000092690
Gene: ENSMUSG00000007476
AA Change: C113R

DomainStartEndE-ValueType
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: C113R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000109284
Gene: ENSMUSG00000007476
AA Change: C113R

DomainStartEndE-ValueType
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: C113R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000139038
Gene: ENSMUSG00000099041
AA Change: C113R

DomainStartEndE-ValueType
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
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.7%
  • 10x: 97.4%
  • 20x: 95.7%
Validation Efficiency
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: 66 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Actr2 A C 11: 20,030,114 (GRCm39) M215R probably benign Het
Ago2 A T 15: 72,996,067 (GRCm39) I354K possibly damaging Het
Angel2 T A 1: 190,673,081 (GRCm39) C72* probably null Het
Ank2 T A 3: 126,797,673 (GRCm39) H679L probably damaging Het
Anks1 A T 17: 28,261,562 (GRCm39) Q694L probably damaging Het
Aox3 C T 1: 58,211,487 (GRCm39) P1015S probably benign Het
Arhgap35 C A 7: 16,296,524 (GRCm39) R847L probably damaging Het
Bag4 C A 8: 26,258,379 (GRCm39) C316F probably damaging Het
Camkv T A 9: 107,824,581 (GRCm39) I258N probably damaging Het
Cpt1c G A 7: 44,620,781 (GRCm39) A28V probably damaging Het
Cyp2j13 A T 4: 95,956,452 (GRCm39) M219K possibly damaging Het
Dclk1 G T 3: 55,154,648 (GRCm39) R26L possibly damaging Het
Diras2 A T 13: 52,662,007 (GRCm39) I100N probably damaging Het
Dnah5 T A 15: 28,448,550 (GRCm39) N4204K probably damaging Het
Dnase1l3 T A 14: 7,987,386 (GRCm38) K55* probably null Het
Dusp6 A G 10: 99,099,864 (GRCm39) D104G possibly damaging Het
Eif5b A G 1: 38,084,468 (GRCm39) T819A probably damaging Het
Elfn2 A T 15: 78,558,073 (GRCm39) L158H probably damaging Het
Erp44 T C 4: 48,196,823 (GRCm39) T367A probably benign Het
Fasn A T 11: 120,707,195 (GRCm39) D843E probably benign Het
Fbxw25 T C 9: 109,493,631 (GRCm39) Y20C probably damaging Het
Fer1l6 G A 15: 58,422,126 (GRCm39) G108E probably damaging Het
Fndc7 C T 3: 108,776,482 (GRCm39) V520I probably benign Het
Gm17019 A G 5: 15,082,817 (GRCm39) W46R possibly damaging Het
Gorab G T 1: 163,214,214 (GRCm39) Q239K probably damaging Het
Gsdma2 A G 11: 98,543,438 (GRCm39) T76A probably benign Het
Hnrnpll A C 17: 80,341,499 (GRCm39) C513W possibly damaging Het
Ifrd2 T C 9: 107,467,824 (GRCm39) L170P probably damaging Het
Itgb4 C T 11: 115,874,983 (GRCm39) R447W probably benign Het
Kcnma1 A G 14: 23,386,106 (GRCm39) probably null Het
Kcnn3 T C 3: 89,516,746 (GRCm39) F385S probably damaging Het
Kif18a T G 2: 109,133,323 (GRCm39) probably null Het
Llgl2 A G 11: 115,741,547 (GRCm39) K559R probably damaging Het
Mgat5 A G 1: 127,387,649 (GRCm39) N535S probably damaging Het
Myh15 T G 16: 48,889,789 (GRCm39) W127G possibly damaging Het
Npsr1 A G 9: 24,046,111 (GRCm39) R77G probably benign Het
Nub1 T A 5: 24,907,446 (GRCm39) S376R probably benign Het
Or14c44 T C 7: 86,062,254 (GRCm39) V228A probably benign Het
Or4d10c G A 19: 12,065,926 (GRCm39) P77S probably damaging Het
Or4k47 A T 2: 111,451,771 (GRCm39) I216N possibly damaging Het
Or5al6 T C 2: 85,976,301 (GRCm39) Y259C probably damaging Het
Or9i2 G A 19: 13,815,680 (GRCm39) P286S probably damaging Het
Pcdh9 A G 14: 94,125,879 (GRCm39) L97P probably damaging Het
Pkn2 A G 3: 142,504,684 (GRCm39) Y831H probably damaging Het
Plcz1 T G 6: 139,985,389 (GRCm39) I51L possibly damaging Het
Plekhg1 T C 10: 3,915,516 (GRCm39) probably benign Het
Prdm9 A T 17: 15,777,713 (GRCm39) S124T probably benign Het
Prkag1 A C 15: 98,713,596 (GRCm39) V33G possibly damaging Het
Rab25 T A 3: 88,450,728 (GRCm39) Y57F possibly damaging Het
Rb1cc1 A G 1: 6,318,545 (GRCm39) I638V probably benign Het
Rest C A 5: 77,416,219 (GRCm39) D144E probably damaging Het
Rpa2 A G 4: 132,505,151 (GRCm39) D260G probably damaging Het
Sf3b3 A G 8: 111,560,467 (GRCm39) V425A probably benign Het
Sidt2 A T 9: 45,863,086 (GRCm39) M15K probably damaging Het
Slc22a17 A G 14: 55,144,748 (GRCm39) L555P probably damaging Het
Smoc2 A G 17: 14,595,719 (GRCm39) D282G possibly damaging Het
Sorcs3 G A 19: 48,748,284 (GRCm39) probably null Het
Spmap2l C T 5: 77,164,317 (GRCm39) P107S probably benign Het
Srcin1 A G 11: 97,464,703 (GRCm39) W15R probably damaging Het
Stra6l A G 4: 45,870,860 (GRCm39) T259A probably benign Het
Ube3a T C 7: 58,938,465 (GRCm39) F741S probably damaging Het
Vasp C A 7: 18,998,594 (GRCm39) M54I probably benign Het
Vmn1r174 A T 7: 23,454,153 (GRCm39) H273L probably benign Het
Vmn2r50 T A 7: 9,771,644 (GRCm39) I686F probably damaging Het
Vmn2r76 T C 7: 85,877,915 (GRCm39) E494G probably benign Het
Zfp788 A G 7: 41,298,753 (GRCm39) E443G probably damaging Het
Other mutations in Lrrc8a
AlleleSourceChrCoordTypePredicted EffectPPH 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
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'- CTACCTTGTAAGTGGGTCACC -3'
(R):5'- TCATCTTGCTGAAGGCTGGC -3'

Sequencing Primer
(F):5'- TGGGTCACCAAAGACTCCTG -3'
(R):5'- CTGGCTTGGGGTCACTCTC -3'
Posted On 2016-07-06