Incidental Mutation 'R1054:Lepr'
ID 94172
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 039144-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R1054 (G1)
Quality Score 225
Status Not validated
Chromosome 4
Chromosomal Location 101574601-101672549 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 101639793 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Threonine at position 753 (I753T)
Ref Sequence ENSEMBL: ENSMUSP00000102534 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000037552] [ENSMUST00000102777] [ENSMUST00000106921]
AlphaFold P48356
Predicted Effect probably damaging
Transcript: ENSMUST00000037552
AA Change: I753T

PolyPhen 2 Score 0.967 (Sensitivity: 0.77; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000037385
Gene: ENSMUSG00000057722
AA Change: I753T

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 damaging
Transcript: ENSMUST00000102777
AA Change: I753T

PolyPhen 2 Score 0.967 (Sensitivity: 0.77; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000099838
Gene: ENSMUSG00000057722
AA Change: I753T

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 damaging
Transcript: ENSMUST00000106921
AA Change: I753T

PolyPhen 2 Score 0.967 (Sensitivity: 0.77; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000102534
Gene: ENSMUSG00000057722
AA Change: I753T

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 noncoding transcript
Transcript: ENSMUST00000128948
Predicted Effect noncoding transcript
Transcript: ENSMUST00000156402
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.4%
  • 10x: 96.7%
  • 20x: 93.9%
Validation Efficiency
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: 46 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Arhgap39 T C 15: 76,635,759 (GRCm39) T159A probably benign Het
Arhgef38 T C 3: 132,822,226 (GRCm39) Y763C probably damaging Het
Arv1 T A 8: 125,458,611 (GRCm39) F245Y probably benign Het
Ccdc175 A G 12: 72,225,318 (GRCm39) I113T possibly damaging Het
Cdc42bpb A T 12: 111,279,787 (GRCm39) M932K probably benign Het
Cdh15 T C 8: 123,591,076 (GRCm39) F442L possibly damaging Het
Col28a1 C T 6: 8,175,534 (GRCm39) D105N probably damaging Het
Cpne4 A G 9: 104,899,600 (GRCm39) T428A probably benign Het
Cramp1 T A 17: 25,202,151 (GRCm39) I444F probably damaging Het
Dhx32 T A 7: 133,327,001 (GRCm39) K360M probably damaging Het
Dna2 T A 10: 62,799,602 (GRCm39) C669S possibly damaging Het
Dusp8 ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGTTGCTGCTGCTGCTGC ACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGTTGCTGCTGCTGCTGC 7: 141,635,804 (GRCm39) probably benign Het
Eif3f G A 7: 108,537,024 (GRCm39) probably null Het
Elmod1 T C 9: 53,820,058 (GRCm39) D310G probably benign Het
Fn1 A G 1: 71,625,373 (GRCm39) *2272Q probably null Het
Gnat1 A G 9: 107,554,638 (GRCm39) S76P probably damaging Het
Gtf2f2 T C 14: 76,232,885 (GRCm39) T94A probably benign Het
Hacd4 A T 4: 88,341,264 (GRCm39) W152R probably damaging Het
Kcnh8 A G 17: 53,110,512 (GRCm39) Y241C probably damaging Het
Med12l C T 3: 59,156,072 (GRCm39) H1162Y probably damaging Het
Med25 C T 7: 44,529,804 (GRCm39) A485T probably benign Het
Mup5 A T 4: 61,750,871 (GRCm39) S145R probably benign Het
Myo1g A G 11: 6,468,987 (GRCm39) V105A probably damaging Het
Npc2 A G 12: 84,807,492 (GRCm39) probably null Het
Or52h1 A G 7: 103,829,498 (GRCm39) I39T probably benign Het
Or6p1 A G 1: 174,258,419 (GRCm39) T142A probably benign Het
Otulinl T C 15: 27,664,635 (GRCm39) R79G probably damaging Het
Pdzd2 A G 15: 12,371,725 (GRCm39) S2557P probably damaging Het
Pop1 T C 15: 34,509,955 (GRCm39) V353A probably benign Het
Pou3f2 A G 4: 22,487,536 (GRCm39) V199A possibly damaging Het
Pramel18 A G 4: 101,766,361 (GRCm39) E15G probably benign Het
Ptprm A T 17: 67,349,313 (GRCm39) N43K probably damaging Het
Qrsl1 C T 10: 43,758,077 (GRCm39) D339N probably damaging Het
Rpl13-ps3 C A 14: 59,131,394 (GRCm39) noncoding transcript Het
Sdk2 C T 11: 113,729,472 (GRCm39) silent Het
Sdr16c6 A G 4: 4,069,908 (GRCm39) V144A probably damaging Het
Spata31d1b C A 13: 59,865,332 (GRCm39) H827N probably damaging Het
Spata31e4 T C 13: 50,856,432 (GRCm39) V690A probably benign Het
Taf4b T A 18: 14,954,530 (GRCm39) H535Q probably benign Het
Timmdc1 A G 16: 38,342,790 (GRCm39) V36A probably benign Het
Tmem74b C T 2: 151,548,339 (GRCm39) A22V probably benign Het
Txnrd3 T A 6: 89,627,543 (GRCm39) Y65* probably null Het
Vmn1r200 T A 13: 22,579,624 (GRCm39) S133R probably damaging Het
Vwf G A 6: 125,567,190 (GRCm39) C311Y probably damaging Het
Wipf2 G A 11: 98,787,141 (GRCm39) R390H possibly damaging Het
Zfp282 T A 6: 47,881,533 (GRCm39) S407T probably benign 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
R0498:Lepr UTSW 4 101,602,889 (GRCm39) missense probably benign 0.01
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
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'- GTGTCACTCACCAATGGGAGAGAAG -3'
(R):5'- GCAAACATTCTGACCAGGCAAGAAG -3'

Sequencing Primer
(F):5'- ATCAGAGTGTGGTTAACAGACTTG -3'
(R):5'- CAGAATTGCCAGTCTACAGTGTC -3'
Posted On 2014-01-05