Mutagenetix > Incidental Mutation

Incidental Mutation 'R0197:Lepr'

23486

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

038456-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R0197 (G1)

Quality Score

192

Status

Validated

Chromosome

Chromosomal Location

101574601-101672549 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 101609349 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Valine at position 312 (D312V)

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: D312V

PolyPhen 2 Score 0.638 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000037385
Gene: ENSMUSG00000057722
AA Change: D312V

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

possibly damaging
Transcript: ENSMUST00000102777
AA Change: D312V

PolyPhen 2 Score 0.638 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000099838
Gene: ENSMUSG00000057722
AA Change: D312V

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000106921
AA Change: D312V

PolyPhen 2 Score 0.638 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000102534
Gene: ENSMUSG00000057722
AA Change: D312V

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

Meta Mutation Damage Score

0.1549

Coding Region Coverage

1x: 98.6%
3x: 97.3%
10x: 92.5%
20x: 75.9%

Validation Efficiency

97% (121/125)

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: 68 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1110002E22Rik	T	C	3: 137,775,632 (GRCm39)	L1607P	probably damaging	Het
1700016H13Rik	T	C	5: 103,796,687 (GRCm39)	*118W	probably null	Het
Abcc2	A	T	19: 43,815,053 (GRCm39)	R1147*	probably null	Het
Acsbg3	A	T	17: 57,190,835 (GRCm39)	N468Y	probably benign	Het
Agap2	A	G	10: 126,927,571 (GRCm39)	T1131A	possibly damaging	Het
Aldh9a1	A	G	1: 167,189,416 (GRCm39)	D388G	probably damaging	Het
Ap3d1	G	T	10: 80,565,876 (GRCm39)	A97E	probably damaging	Het
Arhgef10	T	A	8: 15,012,636 (GRCm39)	V320E	probably damaging	Het
Baiap2l1	C	A	5: 144,202,820 (GRCm39)	V498L	probably damaging	Het
Bltp2	A	C	11: 78,160,530 (GRCm39)		probably benign	Het
Cdh2	T	C	18: 16,762,633 (GRCm39)	N437S	probably benign	Het
Cert1	T	A	13: 96,685,795 (GRCm39)	Y63N	probably benign	Het
Cfap119	T	C	7: 127,184,034 (GRCm39)	E261G	probably damaging	Het
Cfap20dc	C	T	14: 8,518,695 (GRCm38)	G254R	probably damaging	Het
Chd1	C	A	17: 15,945,693 (GRCm39)	N72K	probably benign	Het
Cstf2t	A	T	19: 31,062,026 (GRCm39)	M521L	probably benign	Het
Dlx5	T	C	6: 6,881,619 (GRCm39)	K90E	possibly damaging	Het
Dmp1	A	G	5: 104,355,496 (GRCm39)	E32G	possibly damaging	Het
Espnl	T	G	1: 91,272,211 (GRCm39)	Y524D	probably damaging	Het
Fam20c	T	C	5: 138,741,479 (GRCm39)	L30P	probably damaging	Het
Fat1	G	T	8: 45,479,590 (GRCm39)	A2879S	probably benign	Het
Gabrg1	A	T	5: 70,931,732 (GRCm39)	V337D	probably damaging	Het
Gart	C	A	16: 91,420,291 (GRCm39)	D851Y	possibly damaging	Het
Gcc1	T	C	6: 28,420,615 (GRCm39)	H234R	probably damaging	Het
Gemin6	T	A	17: 80,535,524 (GRCm39)	H161Q	probably damaging	Het
Glt6d1	A	G	2: 25,684,082 (GRCm39)	I308T	probably benign	Het
Gm10320	T	C	13: 98,628,491 (GRCm39)	T7A	probably benign	Het
Gm10912	T	C	2: 103,896,875 (GRCm39)	S5P	probably benign	Het
Gmpr2	T	A	14: 55,910,192 (GRCm39)	D7E	possibly damaging	Het
Hc	A	G	2: 34,874,762 (GRCm39)	Y1620H	probably damaging	Het
Hoxa3	T	C	6: 52,147,123 (GRCm39)		probably benign	Het
Ift140	A	G	17: 25,309,907 (GRCm39)	T1105A	probably benign	Het
Kdr	G	T	5: 76,129,082 (GRCm39)	T188N	possibly damaging	Het
Mcm3	A	G	1: 20,880,329 (GRCm39)	V501A	probably damaging	Het
Mcur1	T	C	13: 43,699,216 (GRCm39)	Y267C	probably damaging	Het
Med13	T	A	11: 86,197,864 (GRCm39)	T736S	probably benign	Het
Med13l	T	C	5: 118,809,067 (GRCm39)		probably benign	Het
Mroh2a	G	C	1: 88,173,764 (GRCm39)	A871P	probably damaging	Het
Ndrg2	T	A	14: 52,144,460 (GRCm39)		probably benign	Het
Oas3	G	A	5: 120,894,210 (GRCm39)	R39C	probably damaging	Het
Onecut2	T	A	18: 64,474,543 (GRCm39)	S365T	possibly damaging	Het
Or13c25	G	A	4: 52,910,849 (GRCm39)	T315M	probably benign	Het
Or4c10	A	G	2: 89,760,545 (GRCm39)	T131A	probably benign	Het
Or4k48	C	T	2: 111,476,136 (GRCm39)	V69I	probably benign	Het
Or51e1	T	A	7: 102,359,202 (GRCm39)	H245Q	probably damaging	Het
Pds5b	C	A	5: 150,677,896 (GRCm39)	Q505K	probably benign	Het
Pramel22	C	T	4: 143,383,010 (GRCm39)	E70K	possibly damaging	Het
Rfx2	T	C	17: 57,110,722 (GRCm39)	Y88C	probably damaging	Het
Rpl6	T	C	5: 121,346,541 (GRCm39)	V214A	probably benign	Het
Samd3	T	A	10: 26,147,752 (GRCm39)	C476S	possibly damaging	Het
Sfi1	TCGC	TC	11: 3,096,254 (GRCm39)		probably null	Het
Shank1	C	T	7: 44,001,718 (GRCm39)	R1146W	unknown	Het
Smcr8	T	C	11: 60,668,941 (GRCm39)	Y30H	probably damaging	Het
Smpd4	T	A	16: 17,459,461 (GRCm39)		probably null	Het
Strip1	C	A	3: 107,521,929 (GRCm39)	D750Y	probably damaging	Het
Svep1	T	C	4: 58,070,851 (GRCm39)	K2312E	possibly damaging	Het
Taf1c	A	T	8: 120,326,722 (GRCm39)	I438N	probably damaging	Het
Tnfaip1	A	T	11: 78,420,840 (GRCm39)		probably benign	Het
Unc45b	T	A	11: 82,831,031 (GRCm39)	L797Q	possibly damaging	Het
Usp24	T	A	4: 106,264,330 (GRCm39)	W1754R	probably damaging	Het
Utp20	G	A	10: 88,613,378 (GRCm39)	P1301L	probably benign	Het
Vmn2r115	T	A	17: 23,578,755 (GRCm39)	S743T	probably damaging	Het
Vps41	T	G	13: 19,038,833 (GRCm39)		probably null	Het
Vps72	G	T	3: 95,029,894 (GRCm39)	L304F	probably damaging	Het
Wiz	A	T	17: 32,575,415 (GRCm39)	I907N	probably damaging	Het
Zfp521	T	C	18: 13,978,119 (GRCm39)	T765A	probably benign	Het
Zfp616	A	T	11: 73,976,500 (GRCm39)	H923L	probably damaging	Het
Zp2	A	T	7: 119,742,799 (GRCm39)		probably benign	Het

Other mutations in Lepr

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
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
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'- GGTCACATTTGTTGCTCGATCTGC -3'
(R):5'- TGTAACTGCACACAGGCACTCC -3'

Sequencing Primer
(F):5'- CAGTTCATCTGTAAGATGATAGCTC -3'
(R):5'- aggaagaatgtcagcccaaag -3'

Posted On

2013-04-16