Incidental Mutation 'R6427:Lepr'
ID 518355
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 044566-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R6427 (G1)
Quality Score 225.009
Status Validated
Chromosome 4
Chromosomal Location 101574601-101672549 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 101631454 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glutamic Acid to Lysine at position 655 (E655K)
Ref Sequence ENSEMBL: ENSMUSP00000102534 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000037552] [ENSMUST00000102777] [ENSMUST00000106921]
AlphaFold P48356
Predicted Effect possibly damaging
Transcript: ENSMUST00000037552
AA Change: E655K

PolyPhen 2 Score 0.471 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000037385
Gene: ENSMUSG00000057722
AA Change: E655K

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 possibly damaging
Transcript: ENSMUST00000102777
AA Change: E655K

PolyPhen 2 Score 0.471 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000099838
Gene: ENSMUSG00000057722
AA Change: E655K

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 possibly damaging
Transcript: ENSMUST00000106921
AA Change: E655K

PolyPhen 2 Score 0.471 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000102534
Gene: ENSMUSG00000057722
AA Change: E655K

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
Meta Mutation Damage Score 0.1138 question?
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.6%
  • 10x: 97.8%
  • 20x: 93.1%
Validation Efficiency 93% (39/42)
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: 40 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abat C T 16: 8,420,300 (GRCm39) probably benign Het
Ankmy2 A G 12: 36,237,710 (GRCm39) S270G possibly damaging Het
Anxa2 T A 9: 69,383,431 (GRCm39) probably null Het
Arid1a G T 4: 133,408,835 (GRCm39) P1891T unknown Het
Atn1 G T 6: 124,723,139 (GRCm39) probably benign Het
Atp8b3 A T 10: 80,356,157 (GRCm39) probably null Het
Cab39l A C 14: 59,743,719 (GRCm39) K94N possibly damaging Het
Cacna2d2 G T 9: 107,392,641 (GRCm39) M528I possibly damaging Het
Ccnc T A 4: 21,747,578 (GRCm39) probably null Het
Cfap251 T C 5: 123,464,596 (GRCm39) L1268P probably damaging Het
Clasp2 C T 9: 113,721,512 (GRCm39) T774I probably damaging Het
Cngb1 C T 8: 96,024,387 (GRCm39) probably benign Het
Cpt1a T A 19: 3,412,156 (GRCm39) F209L probably damaging Het
Cyp2j7 C A 4: 96,115,904 (GRCm39) D181Y probably damaging Het
Daam2 C T 17: 49,776,404 (GRCm39) E828K probably damaging Het
Ddr1 C A 17: 35,998,114 (GRCm39) R477L probably benign Het
Ech1 A G 7: 28,525,310 (GRCm39) T22A probably benign Het
Fbln5 T C 12: 101,728,081 (GRCm39) D294G possibly damaging Het
Fkbp15 T C 4: 62,241,439 (GRCm39) I569V probably benign Het
Hmcn1 G T 1: 150,573,227 (GRCm39) R2141S possibly damaging Het
Kat6b T C 14: 21,567,480 (GRCm39) S180P probably benign Het
Mro T A 18: 74,005,104 (GRCm39) L69Q probably damaging Het
Nipbl A T 15: 8,381,049 (GRCm39) L581H probably benign Het
Nkiras2 C T 11: 100,515,861 (GRCm39) R63W probably damaging Het
Nlrp4e T A 7: 23,020,058 (GRCm39) S182T possibly damaging Het
Obi1 T C 14: 104,717,662 (GRCm39) K237R possibly damaging Het
Or52b4i A T 7: 102,191,895 (GRCm39) I251F probably benign Het
Otud4 T C 8: 80,395,126 (GRCm39) S553P probably benign Het
Pcdha4 T C 18: 37,086,786 (GRCm39) I323T probably benign Het
Polr1b G T 2: 128,965,181 (GRCm39) A756S probably damaging Het
Prex2 A T 1: 11,252,255 (GRCm39) Y1100F probably damaging Het
Serpinb6a A T 13: 34,102,242 (GRCm39) S328T probably damaging Het
Srsf11 C T 3: 157,728,981 (GRCm39) probably benign Het
Stxbp5 T C 10: 9,774,998 (GRCm39) T52A probably damaging Het
Taf3 A T 2: 9,956,164 (GRCm39) F515I probably damaging Het
Unc13b A G 4: 43,176,966 (GRCm39) probably benign Het
Vmn2r106 C T 17: 20,488,725 (GRCm39) C558Y probably damaging Het
Vps51 T C 19: 6,120,947 (GRCm39) Y322C possibly damaging Het
Zfp735 G A 11: 73,581,140 (GRCm39) C59Y possibly damaging Het
Zfp759 A G 13: 67,287,162 (GRCm39) probably null 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
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
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'- TATTGCTGGATCCTCCGGTAG -3'
(R):5'- CTGACAATGTCGATACTCCAGATAGTC -3'

Sequencing Primer
(F):5'- GTCCAATTTTCTGAGGAACCG -3'
(R):5'- GATACTCCAGATAGTCAGCTCTG -3'
Posted On 2018-05-24