Incidental Mutation 'R5253:Lep'
ID 399192
Institutional Source Beutler Lab
Gene Symbol Lep
Ensembl Gene ENSMUSG00000059201
Gene Name leptin
Synonyms
MMRRC Submission 042824-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R5253 (G1)
Quality Score 225
Status Validated
Chromosome 6
Chromosomal Location 29060220-29073875 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 29070862 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Phenylalanine to Tyrosine at position 62 (F62Y)
Ref Sequence ENSEMBL: ENSMUSP00000130087 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000069789] [ENSMUST00000169505]
AlphaFold P41160
Predicted Effect probably damaging
Transcript: ENSMUST00000069789
AA Change: F62Y

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000067046
Gene: ENSMUSG00000059201
AA Change: F62Y

DomainStartEndE-ValueType
signal peptide 1 21 N/A INTRINSIC
Pfam:Leptin 23 167 5.8e-71 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000169505
AA Change: F62Y

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000130087
Gene: ENSMUSG00000059201
AA Change: F62Y

DomainStartEndE-ValueType
signal peptide 1 21 N/A INTRINSIC
Pfam:Leptin 22 98 5.9e-50 PFAM
Meta Mutation Damage Score 0.4536 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.5%
  • 10x: 97.0%
  • 20x: 94.8%
Validation Efficiency 99% (72/73)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein that is secreted by white adipocytes, and which plays a major role in the regulation of body weight. This protein, which acts through the leptin receptor, functions as part of a signaling pathway that can inhibit food intake and/or regulate energy expenditure to maintain constancy of the adipose mass. This protein also has several endocrine functions, and is involved in the regulation of immune and inflammatory responses, hematopoiesis, angiogenesis and wound healing. Mutations in this gene and/or its regulatory regions cause severe obesity, and morbid obesity with hypogonadism. This gene has also been linked to type 2 diabetes mellitus development. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygotes are obese, hyperphagic, have low activity, high metabolic efficiency, impaired thermogenesis, infertility and short lifespan in addition to varying other abnormalities. Strain background affects severity and course of diabetes. Heterozygotes survive fasting longer than control mice. [provided by MGI curators]
Allele List at MGI

All alleles(6) : Targeted(3) Spontaneous(2) Chemically induced(1)

Other mutations in this stock
Total: 65 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700001J11Rik T C 9: 39,962,746 (GRCm39) noncoding transcript Het
Actrt2 A C 4: 154,752,026 (GRCm39) S37A possibly damaging Het
Adcy7 T C 8: 89,040,742 (GRCm39) I327T probably damaging Het
Ankrd13b A G 11: 77,364,061 (GRCm39) probably benign Het
Arap1 A C 7: 101,037,851 (GRCm39) I237L probably benign Het
Arhgap17 A T 7: 122,902,971 (GRCm39) Y359N probably benign Het
Atad1 A G 19: 32,651,702 (GRCm39) M343T probably benign Het
Cacna1b A T 2: 24,609,964 (GRCm39) I392N probably damaging Het
Cacna1c A G 6: 118,574,930 (GRCm39) S1914P probably benign Het
Cd300a G T 11: 114,785,577 (GRCm39) R174L probably benign Het
Dip2a G A 10: 76,135,831 (GRCm39) P356L probably damaging Het
Dsg1c T C 18: 20,405,436 (GRCm39) L283P probably damaging Het
Dusp1 T C 17: 26,727,191 (GRCm39) N36S probably benign Het
Dync2i2 T A 2: 29,922,375 (GRCm39) probably benign Het
Ercc3 C A 18: 32,402,917 (GRCm39) P776Q probably damaging Het
Etv1 A G 12: 38,902,248 (GRCm39) R260G possibly damaging Het
Fa2h C G 8: 112,075,869 (GRCm39) M251I probably benign Het
Fcsk T C 8: 111,610,499 (GRCm39) E968G possibly damaging Het
Flg2 A G 3: 93,108,119 (GRCm39) D49G probably damaging Het
Fras1 A G 5: 96,888,884 (GRCm39) E2810G probably damaging Het
Gabbr1 T C 17: 37,366,805 (GRCm39) F343S possibly damaging Het
Gdf2 A G 14: 33,667,264 (GRCm39) T329A probably benign Het
Hcn4 T A 9: 58,731,558 (GRCm39) I255N unknown Het
Hk3 T G 13: 55,158,824 (GRCm39) D485A probably damaging Het
Hook3 T C 8: 26,562,319 (GRCm39) T249A probably benign Het
Kcp C T 6: 29,498,519 (GRCm39) probably benign Het
Kifc2 G T 15: 76,550,481 (GRCm39) R515L possibly damaging Het
Kiss1r A G 10: 79,756,584 (GRCm39) Y142C probably damaging Het
Klk14 G A 7: 43,341,501 (GRCm39) C51Y probably damaging Het
Klrb1a T A 6: 128,596,126 (GRCm39) I72L probably benign Het
Lrtm1 A G 14: 28,743,801 (GRCm39) T90A probably benign Het
Mug1 A T 6: 121,865,872 (GRCm39) D1472V probably benign Het
Ncor2 G T 5: 125,103,994 (GRCm39) P1988Q probably benign Het
Nlrp4a C T 7: 26,149,917 (GRCm39) S508L probably benign Het
Obp2b T A 2: 25,627,155 (GRCm39) D29E probably benign Het
Or10ag2 G A 2: 87,249,012 (GRCm39) V207M possibly damaging Het
Or4c109 A G 2: 88,818,444 (GRCm39) L34P possibly damaging Het
Or4c119 A T 2: 88,986,801 (GRCm39) C239* probably null Het
Or4k15b T C 14: 50,272,745 (GRCm39) I38M possibly damaging Het
Or6c3b A G 10: 129,527,601 (GRCm39) I103T probably damaging Het
Otof A G 5: 30,527,483 (GRCm39) S1985P probably damaging Het
Oxct2a A T 4: 123,216,886 (GRCm39) V165E probably damaging Het
Pcdhgb7 T C 18: 37,886,150 (GRCm39) V440A possibly damaging Het
Pelp1 C A 11: 70,292,487 (GRCm39) G211C probably damaging Het
Phox2a A G 7: 101,471,312 (GRCm39) H268R probably benign Het
Pik3c2g T C 6: 139,841,983 (GRCm39) probably null Het
Pramel1 T A 4: 143,125,156 (GRCm39) M360K probably benign Het
Rbm6 C T 9: 107,729,856 (GRCm39) R132K probably damaging Het
Slc22a30 G A 19: 8,321,757 (GRCm39) Q436* probably null Het
Slc45a1 T C 4: 150,722,727 (GRCm39) T386A probably damaging Het
Smad2 A G 18: 76,421,124 (GRCm39) Y151C probably damaging Het
Sptbn2 G A 19: 4,800,110 (GRCm39) G2188D probably benign Het
Sugt1 G A 14: 79,840,341 (GRCm39) probably null Het
Tctn3 T C 19: 40,595,685 (GRCm39) S367G probably benign Het
Tead1 G T 7: 112,460,752 (GRCm39) D219Y probably damaging Het
Tenm2 G T 11: 35,938,028 (GRCm39) Y1548* probably null Het
Tenm3 T A 8: 48,682,233 (GRCm39) I2466F possibly damaging Het
Tent4b C A 8: 88,926,651 (GRCm39) H20Q possibly damaging Het
Tgm2 G A 2: 157,971,358 (GRCm39) P294S probably damaging Het
Tns2 T C 15: 102,019,888 (GRCm39) S585P probably damaging Het
Ttc41 A G 10: 86,566,806 (GRCm39) K491E probably benign Het
Ttn G A 2: 76,621,895 (GRCm39) T15549I probably damaging Het
Vmn1r157 T C 7: 22,461,183 (GRCm39) L21P probably damaging Het
Vmn2r81 A G 10: 79,083,820 (GRCm39) M65V probably benign Het
Zcchc14 T C 8: 122,345,433 (GRCm39) probably benign Het
Other mutations in Lep
AlleleSourceChrCoordTypePredicted EffectPPH Score
potbelly UTSW 6 29,068,971 (GRCm39) nonsense probably null
potbelly2 UTSW 6 29,069,089 (GRCm39) missense possibly damaging 0.95
R0009:Lep UTSW 6 29,068,971 (GRCm39) nonsense probably null
R1190:Lep UTSW 6 29,071,173 (GRCm39) nonsense probably null
R1545:Lep UTSW 6 29,070,831 (GRCm39) missense probably damaging 1.00
R1585:Lep UTSW 6 29,069,089 (GRCm39) missense possibly damaging 0.95
R9113:Lep UTSW 6 29,071,093 (GRCm39) missense probably damaging 0.98
R9757:Lep UTSW 6 29,069,083 (GRCm39) missense probably benign 0.07
Z1176:Lep UTSW 6 29,070,969 (GRCm39) missense possibly damaging 0.50
Z1177:Lep UTSW 6 29,071,096 (GRCm39) missense probably damaging 1.00
Z1177:Lep UTSW 6 29,071,095 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- GCTCGGAATGAACAGAAAGTCC -3'
(R):5'- TAGAGTGAGGCTTCCAGGAC -3'

Sequencing Primer
(F):5'- TGGCTCCCAGTCAGCTGATG -3'
(R):5'- TTCTGCAGGCCACTGGTC -3'
Posted On 2016-07-06