Incidental Mutation 'R1398:Lepr'
ID 160220
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 039460-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R1398 (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 101649216 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Glutamic Acid at position 872 (D872E)
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: D872E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000037385
Gene: ENSMUSG00000057722
AA Change: D872E

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: D872E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000099838
Gene: ENSMUSG00000057722
AA Change: D872E

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: D872E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000102534
Gene: ENSMUSG00000057722
AA Change: D872E

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: ENSMUST00000151733
Meta Mutation Damage Score 0.1595 question?
Coding Region Coverage
  • 1x: 99.0%
  • 3x: 98.1%
  • 10x: 95.6%
  • 20x: 90.7%
Validation Efficiency 96% (75/78)
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: 74 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca17 T C 17: 24,547,511 (GRCm39) K288E probably damaging Het
Aldh3a2 T C 11: 61,147,562 (GRCm39) probably null Het
Anks1b A G 10: 89,885,891 (GRCm39) T196A probably damaging Het
Anks6 T A 4: 47,044,926 (GRCm39) T327S possibly damaging Het
Bdh2 T C 3: 135,001,057 (GRCm39) probably benign Het
C4b T A 17: 34,949,693 (GRCm39) probably benign Het
Cacna2d1 G A 5: 16,562,764 (GRCm39) V847I possibly damaging Het
Cadps G T 14: 12,449,822 (GRCm38) T1129K probably damaging Het
Cdc45 A G 16: 18,600,721 (GRCm39) probably benign Het
Cep63 A T 9: 102,480,285 (GRCm39) probably benign Het
Chil4 T A 3: 106,126,825 (GRCm39) probably null Het
Cnot11 A G 1: 39,584,261 (GRCm39) R478G probably damaging Het
Cyp2c67 A G 19: 39,627,069 (GRCm39) S254P probably damaging Het
Dnah11 T A 12: 118,020,841 (GRCm39) K87* probably null Het
Dpy19l2 T A 9: 24,492,559 (GRCm39) probably benign Het
Dsc1 A T 18: 20,221,393 (GRCm39) I694N probably damaging Het
Ehd4 A T 2: 119,958,081 (GRCm39) I168K probably benign Het
Eif4e A T 3: 138,252,136 (GRCm39) N25Y probably damaging Het
Elapor2 A G 5: 9,430,297 (GRCm39) Y69C probably damaging Het
Eme2 G A 17: 25,111,892 (GRCm39) S263F probably damaging Het
Fgfrl1 T A 5: 108,854,147 (GRCm39) probably benign Het
Fhip2a T A 19: 57,361,358 (GRCm39) probably benign Het
Gm3159 T A 14: 4,398,586 (GRCm38) Y92* probably null Het
Gm4922 T A 10: 18,659,496 (GRCm39) S409C possibly damaging Het
Gmcl1 G A 6: 86,691,244 (GRCm39) probably benign Het
Grsf1 A G 5: 88,813,706 (GRCm39) Y231H probably benign Het
Heatr4 T A 12: 84,014,395 (GRCm39) H614L possibly damaging Het
Hoxa13 C G 6: 52,260,647 (GRCm38) probably benign Het
Hoxa13 G C 6: 52,260,648 (GRCm38) probably benign Het
Isg20l2 C A 3: 87,846,061 (GRCm39) L325I probably benign Het
Kalrn A G 16: 34,033,190 (GRCm39) Y879H probably damaging Het
Kcnk10 C A 12: 98,402,485 (GRCm39) W318L probably damaging Het
Kctd1 T C 18: 15,195,654 (GRCm39) E323G possibly damaging Het
Kif4 G T X: 99,732,703 (GRCm39) A492S probably benign Het
Krtap4-1 T C 11: 99,518,558 (GRCm39) T151A unknown Het
Ldlr A T 9: 21,650,838 (GRCm39) Q449L probably benign Het
Lgals12 C T 19: 7,581,322 (GRCm39) probably benign Het
Lrig3 C T 10: 125,838,957 (GRCm39) P488L probably benign Het
Lrrc4b A C 7: 44,111,876 (GRCm39) I583L probably benign Het
Lyst T C 13: 13,915,121 (GRCm39) S3272P possibly damaging Het
Marchf2 T C 17: 33,915,096 (GRCm39) H166R probably damaging Het
Mtbp C A 15: 55,440,933 (GRCm39) Y373* probably null Het
Myh2 C T 11: 67,076,113 (GRCm39) H767Y probably benign Het
Ncam1 G A 9: 49,428,889 (GRCm39) probably benign Het
Neb T A 2: 52,179,658 (GRCm39) N1282Y probably damaging Het
Nectin3 A G 16: 46,269,119 (GRCm39) Y428H possibly damaging Het
Nrros A T 16: 31,961,962 (GRCm39) I649N probably damaging Het
Nvl A T 1: 180,924,691 (GRCm39) probably benign Het
Or5p70 T A 7: 107,994,708 (GRCm39) V127E probably damaging Het
Pms1 A T 1: 53,246,435 (GRCm39) V368E possibly damaging Het
Polq T A 16: 36,882,857 (GRCm39) S1674T possibly damaging Het
Ppp1r21 T C 17: 88,850,307 (GRCm39) V31A probably damaging Het
Rev3l T A 10: 39,697,579 (GRCm39) V692E probably benign Het
Robo4 T C 9: 37,319,372 (GRCm39) probably null Het
Rps6kc1 T C 1: 190,532,212 (GRCm39) I597V probably damaging Het
Rtel1 T A 2: 180,977,658 (GRCm39) probably null Het
Scn9a A G 2: 66,314,930 (GRCm39) M1587T probably benign Het
Sec31b T A 19: 44,512,104 (GRCm39) I597F probably benign Het
Skint5 T C 4: 113,636,268 (GRCm39) N650S unknown Het
Slc22a28 G T 19: 8,107,566 (GRCm39) S167* probably null Het
Slfn1 T A 11: 83,011,968 (GRCm39) M28K probably damaging Het
Smc6 T C 12: 11,321,880 (GRCm39) probably benign Het
Sox8 T C 17: 25,786,857 (GRCm39) H282R probably benign Het
Spata31e2 G T 1: 26,724,422 (GRCm39) Q253K possibly damaging Het
Syngr3 C A 17: 24,905,414 (GRCm39) V161L probably benign Het
Trak1 C T 9: 121,283,425 (GRCm39) S397F probably damaging Het
Uso1 C T 5: 92,329,327 (GRCm39) A405V probably benign Het
Uvrag G T 7: 98,715,027 (GRCm39) Y190* probably null Het
Vps13d A T 4: 144,826,553 (GRCm39) L1726Q probably null Het
Vwf A T 6: 125,580,420 (GRCm39) Q556L probably benign Het
Wdr70 T A 15: 8,065,325 (GRCm39) M246L probably benign Het
Yipf3 T C 17: 46,562,372 (GRCm39) F285S probably damaging Het
Zdhhc13 G A 7: 48,476,621 (GRCm39) G579R probably damaging Het
Zdhhc18 G C 4: 133,354,608 (GRCm39) F125L 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
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
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'- AAATGTGGGTTTGGCCCTACTGAC -3'
(R):5'- TTTAAATGCTGCAAGTGGCACCTTC -3'

Sequencing Primer
(F):5'- TACTGACCTGATCCAGCCG -3'
(R):5'- TGCATCCTGAAGTCAGACTG -3'
Posted On 2014-03-14