Incidental Mutation 'R4546:Lepr'
ID 333760
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 041780-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R4546 (G1)
Quality Score 225
Status Validated
Chromosome 4
Chromosomal Location 101574601-101672549 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 101671838 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Asparagine at position 954 (I954N)
Ref Sequence ENSEMBL: ENSMUSP00000037385 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000037552] [ENSMUST00000106921]
AlphaFold P48356
Predicted Effect probably benign
Transcript: ENSMUST00000037552
AA Change: I954N

PolyPhen 2 Score 0.355 (Sensitivity: 0.90; Specificity: 0.89)
SMART Domains Protein: ENSMUSP00000037385
Gene: ENSMUSG00000057722
AA Change: I954N

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: ENSMUST00000106921
SMART Domains Protein: ENSMUSP00000102534
Gene: ENSMUSG00000057722

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 0.1579 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.5%
  • 10x: 96.8%
  • 20x: 94.0%
Validation Efficiency 97% (65/67)
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: 56 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
9930012K11Rik G A 14: 70,393,927 (GRCm39) S236L probably benign Het
Ahcyl C T 16: 45,974,330 (GRCm39) C349Y possibly damaging Het
Alg9 C T 9: 50,716,654 (GRCm39) T409M possibly damaging Het
Alpi T A 1: 87,026,839 (GRCm39) Y413F probably damaging Het
Asmt T C X: 169,110,230 (GRCm39) probably null Het
Atf7 A G 15: 102,442,762 (GRCm39) V449A probably benign Het
Bnc2 A G 4: 84,210,213 (GRCm39) F744L probably benign Het
Ccnyl1 G T 1: 64,762,735 (GRCm39) M347I probably benign Het
Cdk13 T C 13: 17,941,159 (GRCm39) K21R probably damaging Het
Cenpf A C 1: 189,386,847 (GRCm39) L1811R probably damaging Het
Cfap91 C T 16: 38,155,885 (GRCm39) V113I probably benign Het
Cr2 A G 1: 194,853,349 (GRCm39) I43T possibly damaging Het
Cspg4 T A 9: 56,795,913 (GRCm39) L1216Q possibly damaging Het
Cylc2 A T 4: 51,229,840 (GRCm39) D394V unknown Het
Cylc2 C G 4: 51,229,651 (GRCm39) T331R unknown Het
Dcaf8 T C 1: 172,007,460 (GRCm39) probably benign Het
Dlec1 A T 9: 118,957,146 (GRCm39) I796F probably damaging Het
Dnah12 A T 14: 26,494,971 (GRCm39) Q1343L probably damaging Het
Dnajc21 T C 15: 10,447,183 (GRCm39) R522G probably benign Het
F2rl3 C T 8: 73,489,211 (GRCm39) A146V probably benign Het
Fastkd1 C T 2: 69,542,655 (GRCm39) E51K probably damaging Het
Glrb T C 3: 80,786,993 (GRCm39) S57G probably damaging Het
Gm5507 T A 18: 54,117,409 (GRCm39) noncoding transcript Het
Golga4 A G 9: 118,385,913 (GRCm39) K22E probably damaging Het
Hdac1-ps A T 17: 78,800,388 (GRCm39) T460S probably benign Het
Ift122 T A 6: 115,867,549 (GRCm39) L433Q probably damaging Het
Il21r A G 7: 125,228,071 (GRCm39) R181G probably damaging Het
Il5ra G T 6: 106,715,459 (GRCm39) S125* probably null Het
Kdm7a T C 6: 39,152,406 (GRCm39) R97G probably benign Het
Lims1 T C 10: 58,254,612 (GRCm39) probably benign Het
Mest T C 6: 30,740,679 (GRCm39) W13R probably damaging Het
Mfn2 A G 4: 147,971,909 (GRCm39) V224A probably benign Het
Muc15 T C 2: 110,567,844 (GRCm39) S330P probably damaging Het
Ncapg T C 5: 45,828,554 (GRCm39) F102L probably damaging Het
Nkd2 T C 13: 73,971,475 (GRCm39) D187G probably benign Het
Nphp1 C T 2: 127,607,939 (GRCm39) probably null Het
Or10ag59 T C 2: 87,405,530 (GRCm39) F34S probably benign Het
Or1e19 T C 11: 73,316,012 (GRCm39) N266D probably benign Het
Or2a12 C T 6: 42,904,348 (GRCm39) S61L probably damaging Het
Osbpl6 T C 2: 76,414,836 (GRCm39) V409A possibly damaging Het
Pdhx A T 2: 102,903,742 (GRCm39) L18Q probably null Het
Pear1 C T 3: 87,661,968 (GRCm39) G469D probably damaging Het
Plec T C 15: 76,065,757 (GRCm39) T1506A probably benign Het
Plod3 T A 5: 137,017,801 (GRCm39) D192E possibly damaging Het
Rbks T C 5: 31,781,912 (GRCm39) N296S probably benign Het
Sema3c G A 5: 17,899,770 (GRCm39) V421I probably benign Het
Slc15a4 A G 5: 127,681,600 (GRCm39) probably null Het
Slc7a8 C G 14: 54,973,247 (GRCm39) G240A possibly damaging Het
Tmem200c A G 17: 69,149,166 (GRCm39) D583G probably benign Het
Trpm6 A G 19: 18,809,841 (GRCm39) Y1079C probably damaging Het
Ttn T C 2: 76,652,932 (GRCm39) probably null Het
Vcp T C 4: 42,988,813 (GRCm39) probably benign Het
Vmn2r78 T C 7: 86,603,811 (GRCm39) V663A probably damaging Het
Vmn2r9 T G 5: 108,995,551 (GRCm39) M366L probably benign Het
Wdr11 A G 7: 129,230,729 (GRCm39) E878G probably damaging Het
Zan C G 5: 137,382,096 (GRCm39) M5150I unknown 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
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
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'- CCAAGCATGCAGAATCAGTG -3'
(R):5'- AAATGTCTGGGCCTCTGTC -3'

Sequencing Primer
(F):5'- GCAGAATCAGTGATATTTGGTCCTC -3'
(R):5'- ACTGCCTCAGTGGGGAATGATTAC -3'
Posted On 2015-08-18