Incidental Mutation 'R1585:Lep'
ID 177427
Institutional Source Beutler Lab
Gene Symbol Lep
Ensembl Gene ENSMUSG00000059201
Gene Name leptin
Synonyms
MMRRC Submission 039622-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R1585 (G1)
Quality Score 225
Status Validated
Chromosome 6
Chromosomal Location 29060220-29073875 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to A at 29069089 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Histidine to Asparagine at position 47 (H47N)
Ref Sequence ENSEMBL: ENSMUSP00000130087 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000069789] [ENSMUST00000169505]
AlphaFold P41160
Predicted Effect probably benign
Transcript: ENSMUST00000069789
AA Change: H47N

PolyPhen 2 Score 0.272 (Sensitivity: 0.91; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000067046
Gene: ENSMUSG00000059201
AA Change: H47N

DomainStartEndE-ValueType
signal peptide 1 21 N/A INTRINSIC
Pfam:Leptin 23 167 5.8e-71 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000169505
AA Change: H47N

PolyPhen 2 Score 0.952 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000130087
Gene: ENSMUSG00000059201
AA Change: H47N

DomainStartEndE-ValueType
signal peptide 1 21 N/A INTRINSIC
Pfam:Leptin 22 98 5.9e-50 PFAM
Meta Mutation Damage Score 0.7275 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.1%
  • 10x: 95.7%
  • 20x: 91.2%
Validation Efficiency 95% (81/85)
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: 72 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2310057J18Rik T A 10: 28,858,518 (GRCm39) I50F possibly damaging Het
4930505A04Rik T C 11: 30,377,175 (GRCm39) probably benign Het
Aadat A T 8: 60,979,714 (GRCm39) D192V possibly damaging Het
Akap12 A G 10: 4,303,640 (GRCm39) D150G probably benign Het
Amigo3 A T 9: 107,931,231 (GRCm39) N218I probably damaging Het
Ankmy1 A G 1: 92,827,373 (GRCm39) S60P probably benign Het
Apol7e G A 15: 77,602,029 (GRCm39) S209N probably damaging Het
AW551984 A T 9: 39,510,632 (GRCm39) Y234* probably null Het
Bcam A T 7: 19,494,111 (GRCm39) D393E probably damaging Het
Card9 A G 2: 26,244,398 (GRCm39) L444P probably benign Het
Ccar1 T C 10: 62,586,780 (GRCm39) E886G unknown Het
Ccnb2 A T 9: 70,317,559 (GRCm39) probably null Het
Cd276 T C 9: 58,442,838 (GRCm39) S206G probably damaging Het
Cds1 T A 5: 101,965,828 (GRCm39) probably benign Het
Cfap96 G A 8: 46,409,515 (GRCm39) S268L probably benign Het
Chuk T C 19: 44,065,812 (GRCm39) S661G possibly damaging Het
Col17a1 T C 19: 47,639,276 (GRCm39) N1090D probably benign Het
Col3a1 A T 1: 45,367,026 (GRCm39) probably null Het
Crispld1 G T 1: 17,821,024 (GRCm39) V355F possibly damaging Het
Cspg4 A T 9: 56,806,151 (GRCm39) R2321W probably damaging Het
Dner T C 1: 84,563,177 (GRCm39) T61A probably benign Het
Dnmt3a A T 12: 3,951,660 (GRCm39) Y679F probably damaging Het
Dzip3 A T 16: 48,798,241 (GRCm39) probably benign Het
Eif3l T C 15: 78,968,381 (GRCm39) S217P possibly damaging Het
Fbxo42 T A 4: 140,925,417 (GRCm39) probably benign Het
Fhod1 A T 8: 106,063,957 (GRCm39) probably benign Het
Fzd1 T A 5: 4,806,278 (GRCm39) I435F probably damaging Het
Gapvd1 C T 2: 34,602,207 (GRCm39) V647I possibly damaging Het
Gm14496 T C 2: 181,638,002 (GRCm39) S359P possibly damaging Het
Gm5218 C A 15: 81,383,741 (GRCm39) noncoding transcript Het
Hnrnph3 A G 10: 62,851,579 (GRCm39) probably null Het
Hsd17b12 G T 2: 93,864,321 (GRCm39) T262K probably damaging Het
Igsf10 G C 3: 59,237,838 (GRCm39) P781R probably damaging Het
Il11ra1 T A 4: 41,768,207 (GRCm39) S373T probably damaging Het
Kdm3b A G 18: 34,942,345 (GRCm39) D612G probably damaging Het
Ldb1 T C 19: 46,022,903 (GRCm39) T261A probably damaging Het
Lrrtm2 A T 18: 35,346,428 (GRCm39) S291R possibly damaging Het
Ncor2 T C 5: 125,162,062 (GRCm39) Q404R unknown Het
Nlrp4d T C 7: 10,116,437 (GRCm39) H148R probably benign Het
Nlrp9a T A 7: 26,258,093 (GRCm39) D570E probably benign Het
Nphp3 G A 9: 103,886,413 (GRCm39) V202I probably damaging Het
Nptn T A 9: 58,548,073 (GRCm39) N159K probably benign Het
Or4a69 T A 2: 89,313,315 (GRCm39) T55S probably benign Het
Or4a72 A T 2: 89,405,746 (GRCm39) V108D possibly damaging Het
Or51f2 G A 7: 102,526,980 (GRCm39) V218I probably benign Het
Or52a24 A T 7: 103,381,585 (GRCm39) T151S possibly damaging Het
Or8b53 A T 9: 38,667,716 (GRCm39) H244L probably damaging Het
Pcolce T A 5: 137,608,769 (GRCm39) R13* probably null Het
Pdgfra A G 5: 75,353,264 (GRCm39) Y1018C probably damaging Het
Prima1 A G 12: 103,201,854 (GRCm39) S74P probably damaging Het
Prl7c1 A G 13: 27,962,838 (GRCm39) L55P probably damaging Het
Rasef A G 4: 73,658,574 (GRCm39) V513A probably damaging Het
Rgs1 T C 1: 144,121,227 (GRCm39) probably null Het
Rlf T C 4: 121,005,488 (GRCm39) E1164G probably benign Het
Rnf213 A T 11: 119,354,171 (GRCm39) N4016I probably damaging Het
Sae1 C T 7: 16,064,537 (GRCm39) probably null Het
Serping1 A T 2: 84,601,848 (GRCm39) D207E probably benign Het
Setd2 T A 9: 110,380,464 (GRCm39) D33E unknown Het
Simc1 T C 13: 54,673,071 (GRCm39) M473T probably benign Het
Slc30a6 T A 17: 74,725,610 (GRCm39) probably benign Het
Slc4a5 T C 6: 83,242,669 (GRCm39) L346P probably damaging Het
Spef2 T A 15: 9,596,660 (GRCm39) Q1473L probably damaging Het
St3gal3 G T 4: 117,817,204 (GRCm39) A44D possibly damaging Het
Sv2b G T 7: 74,797,425 (GRCm39) T323K probably damaging Het
Sycp2 T A 2: 177,993,461 (GRCm39) N1228I possibly damaging Het
Thbs2 T A 17: 14,910,030 (GRCm39) M190L probably benign Het
Tnrc6a G A 7: 122,776,098 (GRCm39) V1190I probably benign Het
Utrn A T 10: 12,312,029 (GRCm39) I673K possibly damaging Het
Vmn2r114 C T 17: 23,510,675 (GRCm39) V602M probably damaging Het
Wdr7 A T 18: 64,057,989 (GRCm39) I1273L probably benign Het
Zfp618 T C 4: 63,051,175 (GRCm39) L652P probably damaging Het
Zfp804a G A 2: 81,884,095 (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
R5253:Lep UTSW 6 29,070,862 (GRCm39) missense probably damaging 1.00
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'- ATCCTATAGCAGGATGGCAGCAGG -3'
(R):5'- TTTCAGCAGGCAGCAGTGACAAG -3'

Sequencing Primer
(F):5'- CATATTGGGCTCTTGAAAAGTGTC -3'
(R):5'- AGTGACAAGAGCCATGACC -3'
Posted On 2014-04-24