Incidental Mutation 'R0498:Lepr'
ID 40593
Institutional Source Beutler Lab
Gene Symbol Lepr
Ensembl Gene ENSMUSG00000057722
Gene Name leptin receptor
Synonyms leptin receptor gene-related protein, obl, Obr, Leprb, obese-like, Modb1, LEPROT, OB-RGRP
MMRRC Submission 038694-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R0498 (G1)
Quality Score 225
Status Validated
Chromosome 4
Chromosomal Location 101574601-101672549 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 101602889 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Methionine to Leucine at position 226 (M226L)
Ref Sequence ENSEMBL: ENSMUSP00000102534 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000037552] [ENSMUST00000102777] [ENSMUST00000106921]
AlphaFold P48356
Predicted Effect probably benign
Transcript: ENSMUST00000037552
AA Change: M226L

PolyPhen 2 Score 0.014 (Sensitivity: 0.96; Specificity: 0.79)
SMART Domains Protein: ENSMUSP00000037385
Gene: ENSMUSG00000057722
AA Change: M226L

DomainStartEndE-ValueType
transmembrane domain 7 29 N/A INTRINSIC
FN3 236 315 1.5e-5 SMART
Pfam:Lep_receptor_Ig 328 418 6.3e-23 PFAM
FN3 535 618 4.93e-1 SMART
FN3 641 721 3.25e1 SMART
FN3 736 818 2.35e0 SMART
transmembrane domain 838 860 N/A INTRINSIC
low complexity region 908 921 N/A INTRINSIC
low complexity region 1050 1065 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000102777
AA Change: M226L

PolyPhen 2 Score 0.014 (Sensitivity: 0.96; Specificity: 0.79)
SMART Domains Protein: ENSMUSP00000099838
Gene: ENSMUSG00000057722
AA Change: M226L

DomainStartEndE-ValueType
transmembrane domain 7 29 N/A INTRINSIC
FN3 236 315 1.5e-5 SMART
Pfam:Lep_receptor_Ig 329 420 2.6e-29 PFAM
FN3 535 618 4.93e-1 SMART
FN3 641 721 3.25e1 SMART
FN3 736 818 2.35e0 SMART
transmembrane domain 838 860 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000106921
AA Change: M226L

PolyPhen 2 Score 0.014 (Sensitivity: 0.96; Specificity: 0.79)
SMART Domains Protein: ENSMUSP00000102534
Gene: ENSMUSG00000057722
AA Change: M226L

DomainStartEndE-ValueType
transmembrane domain 7 29 N/A INTRINSIC
FN3 236 315 1.5e-5 SMART
Pfam:Lep_receptor_Ig 329 420 2.6e-29 PFAM
FN3 535 618 4.93e-1 SMART
FN3 641 721 3.25e1 SMART
FN3 736 818 2.35e0 SMART
transmembrane domain 838 860 N/A INTRINSIC
Meta Mutation Damage Score 0.0889 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 96.9%
  • 20x: 94.4%
Validation Efficiency 100% (68/68)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the gp130 family of cytokine receptors that are known to stimulate gene transcription via activation of cytosolic STAT proteins. This protein is a receptor for leptin (an adipocyte-specific hormone that regulates body weight), and is involved in the regulation of fat metabolism, as well as in a novel hematopoietic pathway that is required for normal lymphopoiesis. Mutations in this gene have been associated with obesity and pituitary dysfunction. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. It is noteworthy that this gene and LEPROT gene (GeneID:54741) share the same promoter and the first 2 exons, however, encode distinct proteins (PMID:9207021).[provided by RefSeq, Nov 2010]
PHENOTYPE: Homozygous mutants are hyperphagic, low-activity, poorly cold-adapted, sterile and have enhanced fat conversion. They are obese, hyperinsulinemic and, on certain strains, severely hyperglycemic. Heterozygotes are normal but resistant to prolonged fasting. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 68 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930433I11Rik A T 7: 40,642,718 (GRCm39) D220V probably benign Het
Adgrf2 A G 17: 43,025,206 (GRCm39) probably benign Het
Aldh18a1 A G 19: 40,562,716 (GRCm39) V219A probably benign Het
Anapc10 A G 8: 80,501,610 (GRCm39) D126G probably benign Het
Ap1m2 T C 9: 21,207,129 (GRCm39) *426W probably null Het
Arhgap21 A G 2: 20,867,928 (GRCm39) I865T probably damaging Het
Armc8 A G 9: 99,379,345 (GRCm39) V527A probably damaging Het
Asic5 A T 3: 81,913,778 (GRCm39) probably benign Het
Baz2b A C 2: 59,732,340 (GRCm39) probably benign Het
Bpifa5 T C 2: 154,009,169 (GRCm39) V237A probably damaging Het
Brip1 T A 11: 86,088,745 (GRCm39) K52I possibly damaging Het
Cacna1g T C 11: 94,350,685 (GRCm39) I387V probably damaging Het
Cbr4 A G 8: 61,948,107 (GRCm39) I135V probably benign Het
Ccdc66 C T 14: 27,222,197 (GRCm39) probably null Het
Cubn G A 2: 13,449,078 (GRCm39) T999M probably damaging Het
Dnai3 G T 3: 145,787,119 (GRCm39) D305E possibly damaging Het
Dpp8 C T 9: 64,953,077 (GRCm39) probably benign Het
Dsg1b T C 18: 20,542,390 (GRCm39) S966P possibly damaging Het
Erp27 T C 6: 136,896,862 (GRCm39) probably benign Het
Fat4 A T 3: 39,034,786 (GRCm39) I2813L probably benign Het
Fhod1 G A 8: 106,056,488 (GRCm39) R1101C probably damaging Het
Hoxc9 T C 15: 102,892,359 (GRCm39) S191P probably damaging Het
Izumo4 T C 10: 80,540,030 (GRCm39) probably null Het
Kalrn C T 16: 33,875,261 (GRCm39) D104N possibly damaging Het
Kank4 A T 4: 98,667,873 (GRCm39) D191E probably benign Het
Kbtbd11 A G 8: 15,077,605 (GRCm39) E68G probably benign Het
Kdr C T 5: 76,119,798 (GRCm39) V654I probably benign Het
Klra1 A T 6: 130,349,782 (GRCm39) probably null Het
Kmt2e T A 5: 23,683,970 (GRCm39) Y373* probably null Het
Lrp1b T A 2: 41,348,417 (GRCm39) I800F probably benign Het
Lta4h T C 10: 93,307,833 (GRCm39) probably benign Het
Map3k7 T C 4: 31,974,814 (GRCm39) probably benign Het
Map4k4 G A 1: 40,029,338 (GRCm39) R371Q probably benign Het
Mgat4f A G 1: 134,318,610 (GRCm39) I461V possibly damaging Het
Mme A G 3: 63,253,487 (GRCm39) I444V probably damaging Het
Mms19 C T 19: 41,938,212 (GRCm39) R582Q possibly damaging Het
Mtss1 A G 15: 58,817,286 (GRCm39) S502P probably damaging Het
Myo3a G T 2: 22,467,441 (GRCm39) A232S possibly damaging Het
Nwd2 G T 5: 63,963,686 (GRCm39) W1090L probably damaging Het
Or4k15 A C 14: 50,364,750 (GRCm39) T239P probably damaging Het
Or8b12 G A 9: 37,657,550 (GRCm39) G40E probably damaging Het
Pcm1 G A 8: 41,746,806 (GRCm39) S1335N probably benign Het
Pdzph1 A G 17: 59,280,825 (GRCm39) F486L probably benign Het
Piezo2 T C 18: 63,235,245 (GRCm39) K552R possibly damaging Het
Plekhs1 T A 19: 56,469,536 (GRCm39) probably null Het
Pprc1 C T 19: 46,060,007 (GRCm39) Q1514* probably null Het
Ralgapa1 T C 12: 55,736,576 (GRCm39) T1831A possibly damaging Het
Rnpep G T 1: 135,193,090 (GRCm39) D455E probably damaging Het
Rpgrip1 T A 14: 52,368,771 (GRCm39) probably benign Het
Saxo1 A T 4: 86,397,133 (GRCm39) M135K possibly damaging Het
Serpina12 T C 12: 104,002,048 (GRCm39) T223A probably damaging Het
Serpinb3a A G 1: 106,974,880 (GRCm39) F218L probably damaging Het
Serpinb9f T G 13: 33,509,990 (GRCm39) probably benign Het
Spata33 A G 8: 123,948,662 (GRCm39) D98G probably benign Het
Stard13 T A 5: 150,975,942 (GRCm39) Y742F probably damaging Het
Tecta A G 9: 42,288,910 (GRCm39) Y552H probably damaging Het
Tie1 A T 4: 118,336,358 (GRCm39) probably benign Het
Tmem161a A G 8: 70,633,623 (GRCm39) T254A probably benign Het
Tmem30a G T 9: 79,681,376 (GRCm39) Y264* probably null Het
Tmem87a A T 2: 120,224,946 (GRCm39) I105K probably benign Het
Tnrc6b A T 15: 80,742,920 (GRCm39) D51V probably damaging Het
Trgc3 T A 13: 19,445,262 (GRCm39) M70K probably damaging Het
Trpc4 T C 3: 54,198,632 (GRCm39) F519L probably damaging Het
Ttn T C 2: 76,539,925 (GRCm39) T26027A probably damaging Het
Vmn1r198 A C 13: 22,539,144 (GRCm39) H121P probably damaging Het
Vps33a A G 5: 123,709,024 (GRCm39) F64L probably benign Het
Zfp1008 T C 13: 62,755,201 (GRCm39) N39S probably damaging Het
Zfp994 A T 17: 22,419,882 (GRCm39) C356S probably damaging Het
Other mutations in Lepr
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00089:Lepr APN 4 101,672,232 (GRCm39) missense probably benign
IGL01111:Lepr APN 4 101,671,852 (GRCm39) missense possibly damaging 0.77
IGL01324:Lepr APN 4 101,625,265 (GRCm39) missense probably benign 0.23
IGL01372:Lepr APN 4 101,592,774 (GRCm39) missense possibly damaging 0.67
IGL01626:Lepr APN 4 101,590,731 (GRCm39) missense probably benign 0.10
IGL01733:Lepr APN 4 101,622,279 (GRCm39) missense probably benign 0.00
IGL01815:Lepr APN 4 101,671,987 (GRCm39) missense possibly damaging 0.49
IGL01899:Lepr APN 4 101,637,184 (GRCm39) missense possibly damaging 0.86
IGL02138:Lepr APN 4 101,625,264 (GRCm39) missense probably damaging 0.98
IGL02161:Lepr APN 4 101,602,875 (GRCm39) missense probably damaging 0.97
IGL02653:Lepr APN 4 101,622,141 (GRCm39) missense probably benign 0.44
IGL02735:Lepr APN 4 101,639,835 (GRCm39) missense probably damaging 1.00
IGL03035:Lepr APN 4 101,622,177 (GRCm39) missense probably damaging 1.00
IGL03083:Lepr APN 4 101,671,876 (GRCm39) nonsense probably null
IGL03160:Lepr APN 4 101,622,103 (GRCm39) missense probably damaging 1.00
aufsetzigen UTSW 4 101,609,372 (GRCm39) missense probably damaging 1.00
beastly UTSW 4 101,671,788 (GRCm39) missense probably benign
business_class UTSW 4 101,622,069 (GRCm39) missense probably damaging 1.00
cherub UTSW 4 101,625,259 (GRCm39) missense probably benign 0.25
clodhopper UTSW 4 101,622,487 (GRCm39) splice site probably null
donner UTSW 4 101,672,398 (GRCm39) missense probably damaging 1.00
fluffy UTSW 4 101,649,220 (GRCm39) missense probably damaging 1.00
giant UTSW 4 101,622,349 (GRCm39) critical splice donor site probably null
gordo UTSW 4 101,622,502 (GRCm39) missense probably damaging 0.97
Immunoglutton UTSW 4 101,622,498 (GRCm39) splice site probably benign
Jumbo_shrimp UTSW 4 101,622,151 (GRCm39) nonsense probably null
lowleaning UTSW 4 101,671,588 (GRCm39) splice site probably null
odd UTSW 4 101,585,271 (GRCm39) splice site probably benign
paleo UTSW 4 101,602,842 (GRCm39) missense possibly damaging 0.94
R0140_Lepr_245 UTSW 4 101,625,264 (GRCm39) missense probably damaging 1.00
well-upholstered UTSW 4 101,630,155 (GRCm39) synonymous probably benign
worldly UTSW 4 101,625,425 (GRCm39) missense possibly damaging 0.96
PIT4651001:Lepr UTSW 4 101,649,194 (GRCm39) missense probably damaging 1.00
PIT4696001:Lepr UTSW 4 101,637,180 (GRCm39) missense probably benign 0.10
R0140:Lepr UTSW 4 101,625,264 (GRCm39) missense probably damaging 1.00
R0197:Lepr UTSW 4 101,609,349 (GRCm39) missense possibly damaging 0.64
R0279:Lepr UTSW 4 101,607,541 (GRCm39) missense probably benign 0.05
R0487:Lepr UTSW 4 101,625,290 (GRCm39) nonsense probably null
R0506:Lepr UTSW 4 101,630,207 (GRCm39) splice site probably benign
R0512:Lepr UTSW 4 101,671,901 (GRCm39) missense possibly damaging 0.87
R0512:Lepr UTSW 4 101,649,216 (GRCm39) missense probably damaging 1.00
R0726:Lepr UTSW 4 101,622,131 (GRCm39) missense probably benign 0.01
R1054:Lepr UTSW 4 101,639,793 (GRCm39) missense probably damaging 0.97
R1109:Lepr UTSW 4 101,628,552 (GRCm39) missense probably damaging 1.00
R1398:Lepr UTSW 4 101,649,216 (GRCm39) missense probably damaging 1.00
R1464:Lepr UTSW 4 101,592,878 (GRCm39) missense probably benign 0.08
R1464:Lepr UTSW 4 101,592,878 (GRCm39) missense probably benign 0.08
R1519:Lepr UTSW 4 101,646,541 (GRCm39) missense probably damaging 0.97
R1602:Lepr UTSW 4 101,602,842 (GRCm39) missense possibly damaging 0.94
R1830:Lepr UTSW 4 101,592,874 (GRCm39) missense probably damaging 1.00
R1850:Lepr UTSW 4 101,590,620 (GRCm39) missense possibly damaging 0.67
R1918:Lepr UTSW 4 101,630,033 (GRCm39) missense probably benign 0.08
R1928:Lepr UTSW 4 101,639,927 (GRCm39) splice site probably benign
R2099:Lepr UTSW 4 101,630,185 (GRCm39) missense probably damaging 1.00
R2102:Lepr UTSW 4 101,630,178 (GRCm39) missense possibly damaging 0.95
R2175:Lepr UTSW 4 101,622,576 (GRCm39) missense probably benign 0.01
R2254:Lepr UTSW 4 101,672,309 (GRCm39) missense probably benign 0.26
R2396:Lepr UTSW 4 101,590,725 (GRCm39) missense probably benign 0.19
R2508:Lepr UTSW 4 101,648,093 (GRCm39) missense probably damaging 0.98
R2571:Lepr UTSW 4 101,625,369 (GRCm39) missense possibly damaging 0.96
R3790:Lepr UTSW 4 101,648,111 (GRCm39) splice site probably benign
R3882:Lepr UTSW 4 101,672,462 (GRCm39) missense probably damaging 1.00
R3933:Lepr UTSW 4 101,622,498 (GRCm39) splice site probably benign
R4211:Lepr UTSW 4 101,590,611 (GRCm39) missense probably benign 0.19
R4343:Lepr UTSW 4 101,622,349 (GRCm39) critical splice donor site probably null
R4345:Lepr UTSW 4 101,622,349 (GRCm39) critical splice donor site probably null
R4544:Lepr UTSW 4 101,625,425 (GRCm39) missense possibly damaging 0.96
R4546:Lepr UTSW 4 101,671,838 (GRCm39) missense probably benign 0.35
R4724:Lepr UTSW 4 101,622,562 (GRCm39) nonsense probably null
R4797:Lepr UTSW 4 101,637,244 (GRCm39) missense possibly damaging 0.90
R4860:Lepr UTSW 4 101,646,534 (GRCm39) missense probably benign 0.14
R4860:Lepr UTSW 4 101,646,534 (GRCm39) missense probably benign 0.14
R4929:Lepr UTSW 4 101,672,314 (GRCm39) missense probably benign 0.00
R4939:Lepr UTSW 4 101,590,635 (GRCm39) missense possibly damaging 0.78
R5377:Lepr UTSW 4 101,672,216 (GRCm39) missense possibly damaging 0.71
R5520:Lepr UTSW 4 101,602,734 (GRCm39) missense probably benign 0.00
R5966:Lepr UTSW 4 101,649,324 (GRCm39) intron probably benign
R6092:Lepr UTSW 4 101,649,220 (GRCm39) missense probably damaging 1.00
R6130:Lepr UTSW 4 101,622,569 (GRCm39) missense probably damaging 0.99
R6168:Lepr UTSW 4 101,592,789 (GRCm39) missense probably damaging 0.99
R6232:Lepr UTSW 4 101,671,588 (GRCm39) splice site probably null
R6380:Lepr UTSW 4 101,622,151 (GRCm39) nonsense probably null
R6427:Lepr UTSW 4 101,631,454 (GRCm39) missense possibly damaging 0.47
R6428:Lepr UTSW 4 101,637,295 (GRCm39) missense probably damaging 1.00
R6641:Lepr UTSW 4 101,622,502 (GRCm39) missense probably damaging 0.97
R6650:Lepr UTSW 4 101,672,398 (GRCm39) missense probably damaging 1.00
R6859:Lepr UTSW 4 101,622,487 (GRCm39) splice site probably null
R7023:Lepr UTSW 4 101,646,484 (GRCm39) missense probably damaging 1.00
R7145:Lepr UTSW 4 101,609,394 (GRCm39) missense probably benign 0.00
R7174:Lepr UTSW 4 101,607,535 (GRCm39) missense probably benign 0.01
R7179:Lepr UTSW 4 101,602,856 (GRCm39) missense probably benign 0.06
R7189:Lepr UTSW 4 101,671,961 (GRCm39) missense probably benign 0.00
R7426:Lepr UTSW 4 101,602,853 (GRCm39) missense probably benign 0.03
R7531:Lepr UTSW 4 101,609,372 (GRCm39) missense probably damaging 1.00
R7620:Lepr UTSW 4 101,609,270 (GRCm39) missense probably benign 0.41
R7804:Lepr UTSW 4 101,639,783 (GRCm39) missense probably damaging 1.00
R8022:Lepr UTSW 4 101,639,754 (GRCm39) missense probably benign 0.32
R8142:Lepr UTSW 4 101,622,616 (GRCm39) missense possibly damaging 0.93
R8227:Lepr UTSW 4 101,628,559 (GRCm39) missense probably damaging 0.99
R8426:Lepr UTSW 4 101,671,841 (GRCm39) missense probably benign 0.12
R8447:Lepr UTSW 4 101,671,688 (GRCm39) missense probably benign 0.08
R8531:Lepr UTSW 4 101,622,612 (GRCm39) missense probably damaging 1.00
R8682:Lepr UTSW 4 101,649,269 (GRCm39) missense probably benign 0.00
R8897:Lepr UTSW 4 101,649,233 (GRCm39) missense probably damaging 0.98
R9096:Lepr UTSW 4 101,631,418 (GRCm39) missense possibly damaging 0.95
R9177:Lepr UTSW 4 101,602,798 (GRCm39) nonsense probably null
R9241:Lepr UTSW 4 101,671,788 (GRCm39) missense probably benign
R9604:Lepr UTSW 4 101,590,473 (GRCm39) missense probably benign 0.01
R9711:Lepr UTSW 4 101,592,851 (GRCm39) nonsense probably null
X0026:Lepr UTSW 4 101,590,524 (GRCm39) missense possibly damaging 0.47
Z1176:Lepr UTSW 4 101,602,811 (GRCm39) missense probably damaging 0.99
Z1177:Lepr UTSW 4 101,592,792 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- GTCATAGATGATTCGCCTCTGCCC -3'
(R):5'- TGACTCTGCTCAGTGCTACAGCTC -3'

Sequencing Primer
(F):5'- CTCTGCCCCCACTGAAAG -3'
(R):5'- ACCTTTCAACAGCTTTGCATG -3'
Posted On 2013-05-23