Incidental Mutation 'P0014:Lrrc8c'
ID 7617
Institutional Source Beutler Lab
Gene Symbol Lrrc8c
Ensembl Gene ENSMUSG00000054720
Gene Name leucine rich repeat containing 8 family, member C
Synonyms E430036I04Rik
MMRRC Submission 038267-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # P0014 (G1)
Quality Score
Status Validated
Chromosome 5
Chromosomal Location 105667254-105760884 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 105755110 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Alanine at position 295 (V295A)
Ref Sequence ENSEMBL: ENSMUSP00000066015 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000067924] [ENSMUST00000153754]
AlphaFold Q8R502
Predicted Effect probably benign
Transcript: ENSMUST00000067924
AA Change: V295A

PolyPhen 2 Score 0.060 (Sensitivity: 0.94; Specificity: 0.84)
SMART Domains Protein: ENSMUSP00000066015
Gene: ENSMUSG00000054720
AA Change: V295A

DomainStartEndE-ValueType
Pfam:Pannexin_like 1 338 5.7e-152 PFAM
low complexity region 398 407 N/A INTRINSIC
LRR 588 611 3.97e0 SMART
LRR 613 635 1.81e2 SMART
LRR 636 658 2.2e1 SMART
LRR_TYP 659 682 1.45e-2 SMART
LRR 684 703 3.56e2 SMART
LRR 705 728 2.92e1 SMART
LRR 751 774 1.09e1 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000153754
SMART Domains Protein: ENSMUSP00000114899
Gene: ENSMUSG00000054720

DomainStartEndE-ValueType
Pfam:DUF3733 1 65 4.8e-35 PFAM
low complexity region 78 93 N/A INTRINSIC
Pfam:DUF3733 99 158 1.7e-26 PFAM
Meta Mutation Damage Score 0.0754 question?
Coding Region Coverage
  • 1x: 85.4%
  • 3x: 80.7%
  • 10x: 66.7%
  • 20x: 50.4%
Validation Efficiency 95% (100/105)
MGI Phenotype PHENOTYPE: Mice homozygous for a knock-out allele exhibit a reduction in body weight, white adipose tissue weight, and insulin resistance on a high-fat diet, indicating protection from diet-induced obesity and insulin resistance. [provided by MGI curators]
Allele List at MGI

All alleles(1) : Gene trapped(1)

Other mutations in this stock
Total: 19 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcb4 A G 5: 9,000,083 (GRCm39) Y1017C probably benign Het
Acly T C 11: 100,375,430 (GRCm39) I787V probably benign Het
Aldob T C 4: 49,538,153 (GRCm39) Q325R probably benign Het
Armh4 C T 14: 49,989,116 (GRCm39) E618K probably damaging Het
Capns2 A G 8: 93,628,842 (GRCm39) T244A probably damaging Het
Clec16a C T 16: 10,378,020 (GRCm39) probably benign Het
Creb3 A G 4: 43,563,265 (GRCm39) T121A possibly damaging Het
Ddah1 A G 3: 145,558,913 (GRCm39) D160G probably benign Het
Dhx57 A T 17: 80,582,620 (GRCm39) H328Q probably benign Het
Dmxl2 A C 9: 54,309,048 (GRCm39) L1901R probably damaging Het
Dnah5 T A 15: 28,403,619 (GRCm39) L3448Q probably damaging Het
Gcdh A G 8: 85,615,154 (GRCm39) probably null Het
Nek1 A T 8: 61,524,781 (GRCm39) probably benign Het
Pkp2 C T 16: 16,058,386 (GRCm39) P356L probably benign Het
Sipa1l3 T C 7: 29,082,640 (GRCm39) T752A probably damaging Het
Slc38a2 C A 15: 96,588,042 (GRCm39) W494L probably damaging Het
Ttn T C 2: 76,628,814 (GRCm39) D12734G probably damaging Het
Uggt2 A G 14: 119,281,950 (GRCm39) S742P probably damaging Het
Vwa3b C T 1: 37,212,995 (GRCm39) probably benign Het
Other mutations in Lrrc8c
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00538:Lrrc8c APN 5 105,755,076 (GRCm39) missense probably damaging 0.99
IGL00736:Lrrc8c APN 5 105,754,980 (GRCm39) missense probably damaging 1.00
IGL00822:Lrrc8c APN 5 105,756,174 (GRCm39) missense probably benign 0.04
IGL02009:Lrrc8c APN 5 105,755,257 (GRCm39) missense probably damaging 1.00
IGL02156:Lrrc8c APN 5 105,755,359 (GRCm39) missense probably damaging 1.00
IGL02266:Lrrc8c APN 5 105,756,114 (GRCm39) missense probably benign 0.30
IGL02268:Lrrc8c APN 5 105,755,764 (GRCm39) missense probably damaging 1.00
IGL02487:Lrrc8c APN 5 105,754,457 (GRCm39) missense probably benign
IGL02536:Lrrc8c APN 5 105,755,038 (GRCm39) missense probably benign 0.00
IGL02672:Lrrc8c APN 5 105,755,224 (GRCm39) missense possibly damaging 0.85
IGL02860:Lrrc8c APN 5 105,727,481 (GRCm39) splice site probably benign
IGL03395:Lrrc8c APN 5 105,754,495 (GRCm39) missense probably benign
Hand_grenade UTSW 5 105,754,954 (GRCm39) missense probably damaging 1.00
Horseshoe UTSW 5 105,755,488 (GRCm39) missense probably damaging 1.00
PIT4504001:Lrrc8c UTSW 5 105,756,403 (GRCm39) missense probably benign
PIT4651001:Lrrc8c UTSW 5 105,756,189 (GRCm39) missense probably benign 0.04
R0196:Lrrc8c UTSW 5 105,754,636 (GRCm39) missense probably benign 0.18
R0454:Lrrc8c UTSW 5 105,754,965 (GRCm39) missense probably damaging 1.00
R0565:Lrrc8c UTSW 5 105,754,894 (GRCm39) missense probably damaging 0.98
R0673:Lrrc8c UTSW 5 105,755,544 (GRCm39) missense probably damaging 0.99
R0722:Lrrc8c UTSW 5 105,727,414 (GRCm39) missense probably damaging 1.00
R0815:Lrrc8c UTSW 5 105,756,400 (GRCm39) missense probably damaging 1.00
R1177:Lrrc8c UTSW 5 105,754,702 (GRCm39) missense probably benign 0.40
R1411:Lrrc8c UTSW 5 105,756,045 (GRCm39) missense probably damaging 0.96
R1486:Lrrc8c UTSW 5 105,755,395 (GRCm39) missense probably damaging 1.00
R1551:Lrrc8c UTSW 5 105,756,090 (GRCm39) missense probably damaging 1.00
R1662:Lrrc8c UTSW 5 105,754,623 (GRCm39) missense probably benign 0.22
R1714:Lrrc8c UTSW 5 105,755,157 (GRCm39) missense possibly damaging 0.93
R1770:Lrrc8c UTSW 5 105,754,603 (GRCm39) missense probably damaging 1.00
R2104:Lrrc8c UTSW 5 105,755,224 (GRCm39) missense possibly damaging 0.85
R2139:Lrrc8c UTSW 5 105,754,558 (GRCm39) missense probably damaging 1.00
R4425:Lrrc8c UTSW 5 105,755,755 (GRCm39) missense probably benign 0.22
R4670:Lrrc8c UTSW 5 105,756,240 (GRCm39) missense probably benign
R4897:Lrrc8c UTSW 5 105,755,955 (GRCm39) missense probably benign 0.01
R4968:Lrrc8c UTSW 5 105,754,993 (GRCm39) missense probably damaging 1.00
R5114:Lrrc8c UTSW 5 105,755,349 (GRCm39) missense probably damaging 1.00
R5580:Lrrc8c UTSW 5 105,755,553 (GRCm39) missense probably benign 0.00
R5804:Lrrc8c UTSW 5 105,727,423 (GRCm39) missense possibly damaging 0.88
R5918:Lrrc8c UTSW 5 105,756,117 (GRCm39) missense possibly damaging 0.68
R6293:Lrrc8c UTSW 5 105,754,612 (GRCm39) missense probably damaging 1.00
R6303:Lrrc8c UTSW 5 105,756,475 (GRCm39) missense probably benign 0.31
R6304:Lrrc8c UTSW 5 105,756,475 (GRCm39) missense probably benign 0.31
R7271:Lrrc8c UTSW 5 105,755,853 (GRCm39) missense probably benign 0.02
R7341:Lrrc8c UTSW 5 105,755,133 (GRCm39) missense probably damaging 1.00
R7380:Lrrc8c UTSW 5 105,755,701 (GRCm39) missense possibly damaging 0.71
R7630:Lrrc8c UTSW 5 105,755,568 (GRCm39) missense probably damaging 0.99
R7789:Lrrc8c UTSW 5 105,755,066 (GRCm39) missense probably damaging 1.00
R8128:Lrrc8c UTSW 5 105,755,488 (GRCm39) missense probably damaging 1.00
R8229:Lrrc8c UTSW 5 105,754,402 (GRCm39) missense probably benign 0.00
R8247:Lrrc8c UTSW 5 105,756,310 (GRCm39) missense probably damaging 1.00
R8248:Lrrc8c UTSW 5 105,755,733 (GRCm39) missense probably benign
R8890:Lrrc8c UTSW 5 105,754,954 (GRCm39) missense probably damaging 1.00
R9254:Lrrc8c UTSW 5 105,756,356 (GRCm39) nonsense probably null
R9379:Lrrc8c UTSW 5 105,756,356 (GRCm39) nonsense probably null
R9416:Lrrc8c UTSW 5 105,756,163 (GRCm39) missense possibly damaging 0.95
Protein Function and Prediction

Leucine-rich repeat (LRR)-containing protein 8c [Lrrc8c; alternatively factor for adipocyte differentiation 158 (Fad158)] is in the LRR family of proteins that mediate protein-protein interactions in several physiological processes.  LRR8C has been identified as essential for B cell development (1).  Also, LRR8C expression is essential during early adipocyte differentiation via an interaction with PPAR-gamma (2).  Lrr8c is considered to be essential in the development of obesity and insulin resistance caused by high-fat diet (3).

Expression/Localization

Examination of LRRC8C by semiquantitative PCR found that it is expressed in all tissues except skeletal muscle; highest expression was found in the heart, brain, placenta, and lung (1).  Expression was observed in both T and B cells (1).  In contrast, another study, using Northern blot of human tissues, found moderate expression of LRRC8C in the heart, lung, and peripheral blood leukocytes; high expression was observed in skeletal muscle (2). This study observed LRRC8C expression was localized to the endoplasmic reticulum (2).

Background

Gene disruption prevents the body weight gain and insulin resistance induced by a high-fat diet (in vitro) (3). Lrrc8c-deficient mice had significantly lower body weights and fat mass than wild-type animals when give a high-fat diet; the animals did not have changes in body weight on a normal diet (3).

References
Posted On 2012-10-05
Science Writer Anne Murray