Mutagenetix > Incidental Mutation

Incidental Mutation 'R5377:Lepr'

425603

Institutional Source

Beutler Lab

Gene Symbol

Lepr

Ensembl Gene

ENSMUSG00000057722

Gene Name

leptin receptor

Synonyms

obl, Leprb, Obr, obese-like, OB-RGRP, Modb1, leptin receptor gene-related protein, LEPROT

MMRRC Submission

042845-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R5377 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

101717404-101815352 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 101815019 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 1080 (V1080A)

Ref Sequence

ENSEMBL: ENSMUSP00000037385 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000037552] [ENSMUST00000106921]

AlphaFold

P48356

Predicted Effect

possibly damaging
Transcript: ENSMUST00000037552
AA Change: V1080A

PolyPhen 2 Score 0.714 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000037385
Gene: ENSMUSG00000057722
AA Change: V1080A

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
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

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.4%
20x: 95.5%

Validation Efficiency

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: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A2m	G	T	6: 121,645,253 (GRCm38)	V372F	probably benign	Het
Adcy10	G	A	1: 165,519,895 (GRCm38)	C393Y	probably damaging	Het
Adgrg7	A	C	16: 56,730,306 (GRCm38)	I681S	possibly damaging	Het
Akap8l	T	C	17: 32,321,511 (GRCm38)		probably benign	Het
Akr1a1	A	T	4: 116,639,895 (GRCm38)	V156E	probably damaging	Het
Alk	T	G	17: 71,895,739 (GRCm38)	D1167A	probably damaging	Het
Ankrd11	T	C	8: 122,893,714 (GRCm38)		probably null	Het
Aspm	T	A	1: 139,457,483 (GRCm38)	N288K	probably damaging	Het
Aspm	A	G	1: 139,470,395 (GRCm38)		probably null	Het
Asxl2	G	A	12: 3,474,618 (GRCm38)		probably null	Het
Atp6v0a1	A	G	11: 101,055,587 (GRCm38)	H802R	probably damaging	Het
B4galnt1	A	G	10: 127,171,822 (GRCm38)	T531A	possibly damaging	Het
Ccdc114	C	T	7: 45,942,082 (GRCm38)	R257*	probably null	Het
Cecr2	A	G	6: 120,756,569 (GRCm38)	N506D	possibly damaging	Het
Crebrf	T	C	17: 26,759,865 (GRCm38)	V509A	probably damaging	Het
Cyp4f40	A	T	17: 32,675,616 (GRCm38)	I413F	probably null	Het
Defb12	C	A	8: 19,114,326 (GRCm38)		probably null	Het
Dnah2	T	C	11: 69,421,848 (GRCm38)	E4297G	probably damaging	Het
Dpysl5	A	T	5: 30,791,513 (GRCm38)	N371Y	probably damaging	Het
Eef1d	G	T	15: 75,903,189 (GRCm38)	T207N	probably benign	Het
Esrrb	C	T	12: 86,519,009 (GRCm38)	Q416*	probably null	Het
Exd2	T	C	12: 80,489,448 (GRCm38)	L284P	probably damaging	Het
Fat3	T	A	9: 16,376,443 (GRCm38)	I595F	probably benign	Het
Gm9920	A	G	15: 55,108,975 (GRCm38)		probably benign	Het
Hephl1	T	C	9: 15,069,788 (GRCm38)	K783E	probably damaging	Het
Irs2	A	G	8: 11,005,277 (GRCm38)	S1052P	probably benign	Het
Kctd18	T	C	1: 57,963,093 (GRCm38)	I192V	probably benign	Het
Lama3	A	G	18: 12,453,746 (GRCm38)	D722G	probably damaging	Het
Lpin1	C	T	12: 16,563,655 (GRCm38)	G504S	probably damaging	Het
Lrit2	A	C	14: 37,069,183 (GRCm38)	Q273P	possibly damaging	Het
Mgea5	A	T	19: 45,758,022 (GRCm38)	Y779*	probably null	Het
Mlkl	T	A	8: 111,327,937 (GRCm38)	E189D	probably benign	Het
Mttp	C	T	3: 138,105,029 (GRCm38)	R608H	probably benign	Het
Nav2	T	C	7: 49,589,160 (GRCm38)	V2011A	probably benign	Het
Nos2	A	T	11: 78,957,491 (GRCm38)	I1075F	probably benign	Het
Npat	A	G	9: 53,550,036 (GRCm38)		probably null	Het
Nucks1	T	C	1: 131,919,033 (GRCm38)	F16L	probably damaging	Het
Nus1	T	C	10: 52,429,213 (GRCm38)	S150P	possibly damaging	Het
Olfr1230	G	T	2: 89,297,162 (GRCm38)	T36K	probably damaging	Het
Olfr881	A	T	9: 37,992,612 (GRCm38)	Y40F	probably benign	Het
Pclo	A	G	5: 14,681,353 (GRCm38)	T3290A	unknown	Het
Pign	A	T	1: 105,657,812 (GRCm38)	F4Y	probably benign	Het
Rfx4	A	G	10: 84,860,542 (GRCm38)	N233D	possibly damaging	Het
Rpgrip1	A	T	14: 52,160,195 (GRCm38)	M1325L	possibly damaging	Het
Rufy4	T	C	1: 74,147,663 (GRCm38)	C537R	probably damaging	Het
Scaf11	T	A	15: 96,417,120 (GRCm38)	H1227L	possibly damaging	Het
Sec31b	G	T	19: 44,518,637 (GRCm38)	P840T	probably damaging	Het
Slc16a9	T	A	10: 70,283,128 (GRCm38)	L426I	probably damaging	Het
Slc17a2	T	C	13: 23,812,592 (GRCm38)	S27P	probably damaging	Het
Slc22a30	G	A	19: 8,344,393 (GRCm38)	Q436*	probably null	Het
Tacc1	A	G	8: 25,182,283 (GRCm38)	S310P	possibly damaging	Het
Tmem245	G	A	4: 56,947,084 (GRCm38)	R110C	probably damaging	Het
Trip12	T	C	1: 84,757,431 (GRCm38)	Y953C	probably damaging	Het
Trpm7	C	A	2: 126,842,855 (GRCm38)		probably null	Het
Ush2a	G	A	1: 188,912,123 (GRCm38)	V4561I	probably benign	Het
Vmn1r192	C	T	13: 22,187,631 (GRCm38)	V140I	probably benign	Het
Vmn2r66	A	T	7: 85,006,818 (GRCm38)	I330N	probably damaging	Het
Vmn2r99	T	C	17: 19,379,269 (GRCm38)	V405A	probably damaging	Het
Wdhd1	A	C	14: 47,272,221 (GRCm38)	V172G	probably benign	Het
Zfhx3	C	T	8: 108,951,185 (GRCm38)	R2956C	possibly damaging	Het
Zfp446	T	C	7: 12,982,251 (GRCm38)	L283P	possibly damaging	Het
Zfp82	T	C	7: 30,057,166 (GRCm38)	K164E	probably damaging	Het

Other mutations in Lepr

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00089:Lepr	APN	4	101,815,035 (GRCm38)	missense	probably benign
IGL01111:Lepr	APN	4	101,814,655 (GRCm38)	missense	possibly damaging	0.77
IGL01324:Lepr	APN	4	101,768,068 (GRCm38)	missense	probably benign	0.23
IGL01372:Lepr	APN	4	101,735,577 (GRCm38)	missense	possibly damaging	0.67
IGL01626:Lepr	APN	4	101,733,534 (GRCm38)	missense	probably benign	0.10
IGL01733:Lepr	APN	4	101,765,082 (GRCm38)	missense	probably benign	0.00
IGL01815:Lepr	APN	4	101,814,790 (GRCm38)	missense	possibly damaging	0.49
IGL01899:Lepr	APN	4	101,779,987 (GRCm38)	missense	possibly damaging	0.86
IGL02138:Lepr	APN	4	101,768,067 (GRCm38)	missense	probably damaging	0.98
IGL02161:Lepr	APN	4	101,745,678 (GRCm38)	missense	probably damaging	0.97
IGL02653:Lepr	APN	4	101,764,944 (GRCm38)	missense	probably benign	0.44
IGL02735:Lepr	APN	4	101,782,638 (GRCm38)	missense	probably damaging	1.00
IGL03035:Lepr	APN	4	101,764,980 (GRCm38)	missense	probably damaging	1.00
IGL03083:Lepr	APN	4	101,814,679 (GRCm38)	nonsense	probably null
IGL03160:Lepr	APN	4	101,764,906 (GRCm38)	missense	probably damaging	1.00
aufsetzigen	UTSW	4	101,752,175 (GRCm38)	missense	probably damaging	1.00
beastly	UTSW	4	101,814,591 (GRCm38)	missense	probably benign
business_class	UTSW	4	101,764,872 (GRCm38)	missense	probably damaging	1.00
cherub	UTSW	4	101,768,062 (GRCm38)	missense	probably benign	0.25
clodhopper	UTSW	4	101,765,290 (GRCm38)	splice site	probably null
donner	UTSW	4	101,815,201 (GRCm38)	missense	probably damaging	1.00
fluffy	UTSW	4	101,792,023 (GRCm38)	missense	probably damaging	1.00
giant	UTSW	4	101,765,152 (GRCm38)	critical splice donor site	probably null
gordo	UTSW	4	101,765,305 (GRCm38)	missense	probably damaging	0.97
Immunoglutton	UTSW	4	101,765,301 (GRCm38)	splice site	probably benign
Jumbo_shrimp	UTSW	4	101,764,954 (GRCm38)	nonsense	probably null
lowleaning	UTSW	4	101,814,391 (GRCm38)	splice site	probably null
odd	UTSW	4	101,728,074 (GRCm38)	splice site	probably benign
paleo	UTSW	4	101,745,645 (GRCm38)	missense	possibly damaging	0.94
R0140_Lepr_245	UTSW	4	101,768,067 (GRCm38)	missense	probably damaging	1.00
well-upholstered	UTSW	4	101,772,958 (GRCm38)	synonymous	probably benign
worldly	UTSW	4	101,768,228 (GRCm38)	missense	possibly damaging	0.96
PIT4651001:Lepr	UTSW	4	101,791,997 (GRCm38)	missense	probably damaging	1.00
PIT4696001:Lepr	UTSW	4	101,779,983 (GRCm38)	missense	probably benign	0.10
R0140:Lepr	UTSW	4	101,768,067 (GRCm38)	missense	probably damaging	1.00
R0197:Lepr	UTSW	4	101,752,152 (GRCm38)	missense	possibly damaging	0.64
R0279:Lepr	UTSW	4	101,750,344 (GRCm38)	missense	probably benign	0.05
R0487:Lepr	UTSW	4	101,768,093 (GRCm38)	nonsense	probably null
R0498:Lepr	UTSW	4	101,745,692 (GRCm38)	missense	probably benign	0.01
R0506:Lepr	UTSW	4	101,773,010 (GRCm38)	splice site	probably benign
R0512:Lepr	UTSW	4	101,814,704 (GRCm38)	missense	possibly damaging	0.87
R0512:Lepr	UTSW	4	101,792,019 (GRCm38)	missense	probably damaging	1.00
R0726:Lepr	UTSW	4	101,764,934 (GRCm38)	missense	probably benign	0.01
R1054:Lepr	UTSW	4	101,782,596 (GRCm38)	missense	probably damaging	0.97
R1109:Lepr	UTSW	4	101,771,355 (GRCm38)	missense	probably damaging	1.00
R1398:Lepr	UTSW	4	101,792,019 (GRCm38)	missense	probably damaging	1.00
R1464:Lepr	UTSW	4	101,735,681 (GRCm38)	missense	probably benign	0.08
R1464:Lepr	UTSW	4	101,735,681 (GRCm38)	missense	probably benign	0.08
R1519:Lepr	UTSW	4	101,789,344 (GRCm38)	missense	probably damaging	0.97
R1602:Lepr	UTSW	4	101,745,645 (GRCm38)	missense	possibly damaging	0.94
R1830:Lepr	UTSW	4	101,735,677 (GRCm38)	missense	probably damaging	1.00
R1850:Lepr	UTSW	4	101,733,423 (GRCm38)	missense	possibly damaging	0.67
R1918:Lepr	UTSW	4	101,772,836 (GRCm38)	missense	probably benign	0.08
R1928:Lepr	UTSW	4	101,782,730 (GRCm38)	splice site	probably benign
R2099:Lepr	UTSW	4	101,772,988 (GRCm38)	missense	probably damaging	1.00
R2102:Lepr	UTSW	4	101,772,981 (GRCm38)	missense	possibly damaging	0.95
R2175:Lepr	UTSW	4	101,765,379 (GRCm38)	missense	probably benign	0.01
R2254:Lepr	UTSW	4	101,815,112 (GRCm38)	missense	probably benign	0.26
R2396:Lepr	UTSW	4	101,733,528 (GRCm38)	missense	probably benign	0.19
R2508:Lepr	UTSW	4	101,790,896 (GRCm38)	missense	probably damaging	0.98
R2571:Lepr	UTSW	4	101,768,172 (GRCm38)	missense	possibly damaging	0.96
R3790:Lepr	UTSW	4	101,790,914 (GRCm38)	splice site	probably benign
R3882:Lepr	UTSW	4	101,815,265 (GRCm38)	missense	probably damaging	1.00
R3933:Lepr	UTSW	4	101,765,301 (GRCm38)	splice site	probably benign
R4211:Lepr	UTSW	4	101,733,414 (GRCm38)	missense	probably benign	0.19
R4343:Lepr	UTSW	4	101,765,152 (GRCm38)	critical splice donor site	probably null
R4345:Lepr	UTSW	4	101,765,152 (GRCm38)	critical splice donor site	probably null
R4544:Lepr	UTSW	4	101,768,228 (GRCm38)	missense	possibly damaging	0.96
R4546:Lepr	UTSW	4	101,814,641 (GRCm38)	missense	probably benign	0.35
R4724:Lepr	UTSW	4	101,765,365 (GRCm38)	nonsense	probably null
R4797:Lepr	UTSW	4	101,780,047 (GRCm38)	missense	possibly damaging	0.90
R4860:Lepr	UTSW	4	101,789,337 (GRCm38)	missense	probably benign	0.14
R4860:Lepr	UTSW	4	101,789,337 (GRCm38)	missense	probably benign	0.14
R4929:Lepr	UTSW	4	101,815,117 (GRCm38)	missense	probably benign	0.00
R4939:Lepr	UTSW	4	101,733,438 (GRCm38)	missense	possibly damaging	0.78
R5520:Lepr	UTSW	4	101,745,537 (GRCm38)	missense	probably benign	0.00
R5966:Lepr	UTSW	4	101,792,127 (GRCm38)	intron	probably benign
R6092:Lepr	UTSW	4	101,792,023 (GRCm38)	missense	probably damaging	1.00
R6130:Lepr	UTSW	4	101,765,372 (GRCm38)	missense	probably damaging	0.99
R6168:Lepr	UTSW	4	101,735,592 (GRCm38)	missense	probably damaging	0.99
R6232:Lepr	UTSW	4	101,814,391 (GRCm38)	splice site	probably null
R6380:Lepr	UTSW	4	101,764,954 (GRCm38)	nonsense	probably null
R6427:Lepr	UTSW	4	101,774,257 (GRCm38)	missense	possibly damaging	0.47
R6428:Lepr	UTSW	4	101,780,098 (GRCm38)	missense	probably damaging	1.00
R6641:Lepr	UTSW	4	101,765,305 (GRCm38)	missense	probably damaging	0.97
R6650:Lepr	UTSW	4	101,815,201 (GRCm38)	missense	probably damaging	1.00
R6859:Lepr	UTSW	4	101,765,290 (GRCm38)	splice site	probably null
R7023:Lepr	UTSW	4	101,789,287 (GRCm38)	missense	probably damaging	1.00
R7145:Lepr	UTSW	4	101,752,197 (GRCm38)	missense	probably benign	0.00
R7174:Lepr	UTSW	4	101,750,338 (GRCm38)	missense	probably benign	0.01
R7179:Lepr	UTSW	4	101,745,659 (GRCm38)	missense	probably benign	0.06
R7189:Lepr	UTSW	4	101,814,764 (GRCm38)	missense	probably benign	0.00
R7426:Lepr	UTSW	4	101,745,656 (GRCm38)	missense	probably benign	0.03
R7531:Lepr	UTSW	4	101,752,175 (GRCm38)	missense	probably damaging	1.00
R7620:Lepr	UTSW	4	101,752,073 (GRCm38)	missense	probably benign	0.41
R7804:Lepr	UTSW	4	101,782,586 (GRCm38)	missense	probably damaging	1.00
R8022:Lepr	UTSW	4	101,782,557 (GRCm38)	missense	probably benign	0.32
R8142:Lepr	UTSW	4	101,765,419 (GRCm38)	missense	possibly damaging	0.93
R8227:Lepr	UTSW	4	101,771,362 (GRCm38)	missense	probably damaging	0.99
R8426:Lepr	UTSW	4	101,814,644 (GRCm38)	missense	probably benign	0.12
R8447:Lepr	UTSW	4	101,814,491 (GRCm38)	missense	probably benign	0.08
R8531:Lepr	UTSW	4	101,765,415 (GRCm38)	missense	probably damaging	1.00
R8682:Lepr	UTSW	4	101,792,072 (GRCm38)	missense	probably benign	0.00
R8897:Lepr	UTSW	4	101,792,036 (GRCm38)	missense	probably damaging	0.98
R9096:Lepr	UTSW	4	101,774,221 (GRCm38)	missense	possibly damaging	0.95
R9177:Lepr	UTSW	4	101,745,601 (GRCm38)	nonsense	probably null
R9241:Lepr	UTSW	4	101,814,591 (GRCm38)	missense	probably benign
R9604:Lepr	UTSW	4	101,733,276 (GRCm38)	missense	probably benign	0.01
R9711:Lepr	UTSW	4	101,735,654 (GRCm38)	nonsense	probably null
X0026:Lepr	UTSW	4	101,733,327 (GRCm38)	missense	possibly damaging	0.47
Z1176:Lepr	UTSW	4	101,745,614 (GRCm38)	missense	probably damaging	0.99
Z1177:Lepr	UTSW	4	101,735,595 (GRCm38)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CCTGTCAGCAACTGCATCTC -3'
(R):5'- GGCATGTAAGGTACAAAGTTCTCAC -3'

Sequencing Primer
(F):5'- ACTGAGGCAGTCTTTCTCTAGCAG -3'
(R):5'- GGTACAAAGTTCTCACCAGAGGTC -3'

Posted On

2016-08-04