Mutagenetix > Incidental Mutation

Incidental Mutation 'PIT4696001:Lepr'

556777

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

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

PIT4696001 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

101717404-101815352 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 101779983 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Serine to Alanine at position 690 (S690A)

Ref Sequence

ENSEMBL: ENSMUSP00000037385 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000037552] [ENSMUST00000102777] [ENSMUST00000106921]

AlphaFold

P48356

Predicted Effect

probably benign
Transcript: ENSMUST00000037552
AA Change: S690A

PolyPhen 2 Score 0.102 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000037385
Gene: ENSMUSG00000057722
AA Change: S690A

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: ENSMUST00000102777
AA Change: S690A

PolyPhen 2 Score 0.047 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000099838
Gene: ENSMUSG00000057722
AA Change: S690A

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

probably benign
Transcript: ENSMUST00000106921
AA Change: S690A

PolyPhen 2 Score 0.163 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000102534
Gene: ENSMUSG00000057722
AA Change: S690A

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: 93.5%
3x: 91.0%
10x: 86.2%
20x: 75.9%

Validation Efficiency

100% (57/57)

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: 58 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acsm3	G	A	7: 119,784,986 (GRCm38)		probably null	Het
Adam20	T	A	8: 40,794,948 (GRCm38)	Y32N	probably benign	Het
Adm	T	C	7: 110,628,289 (GRCm38)	V4A	probably benign	Het
Anpep	G	A	7: 79,839,464 (GRCm38)	T320I	possibly damaging	Het
Atp8b1	T	C	18: 64,539,270 (GRCm38)	S1008G	possibly damaging	Het
B9d1	T	A	11: 61,505,243 (GRCm38)	M12K	possibly damaging	Het
Cad	T	C	5: 31,072,094 (GRCm38)	L1435P	probably damaging	Het
Cat	T	C	2: 103,471,812 (GRCm38)	D180G	probably damaging	Het
Cntln	C	T	4: 84,974,000 (GRCm38)	T374M	probably damaging	Het
Cyp2a5	G	A	7: 26,840,979 (GRCm38)	R339Q	probably benign	Het
Defa22	T	C	8: 21,162,336 (GRCm38)	L6P	probably damaging	Het
Dr1	T	A	5: 108,269,738 (GRCm38)	I50K	probably damaging	Het
Eln	C	T	5: 134,737,178 (GRCm38)	G57E	unknown	Het
Fat4	T	C	3: 38,889,004 (GRCm38)	I682T	probably benign	Het
Fat4	C	A	3: 38,982,357 (GRCm38)	A3386E	probably damaging	Het
Fcgr3	T	A	1: 171,057,750 (GRCm38)	Y102F	probably damaging	Het
Gm5930	A	T	14: 44,336,536 (GRCm38)	L115M	probably damaging	Het
Herc1	T	A	9: 66,479,009 (GRCm38)	V3748D	probably damaging	Het
Ino80d	A	G	1: 63,085,986 (GRCm38)	S106P	probably benign	Het
Kcns3	C	T	12: 11,092,748 (GRCm38)		probably benign	Het
Kndc1	T	A	7: 139,932,917 (GRCm38)	L1527Q	probably damaging	Het
Lrfn5	T	C	12: 61,843,557 (GRCm38)	F544S	probably damaging	Het
Mapkap1	C	A	2: 34,619,849 (GRCm38)	H450Q	probably damaging	Het
Mdm1	A	G	10: 118,158,540 (GRCm38)	T485A	probably benign	Het
Megf10	T	C	18: 57,277,688 (GRCm38)	C690R	probably damaging	Het
Myo7a	A	G	7: 98,063,599 (GRCm38)	M1723T	probably benign	Het
Nrip3	A	T	7: 109,765,507 (GRCm38)	C137*	probably null	Het
Olfr153	T	A	2: 87,532,780 (GRCm38)	I249N	probably damaging	Het
Pde4a	T	A	9: 21,211,001 (GRCm38)	M731K	probably benign	Het
Pebp1	A	G	5: 117,283,462 (GRCm38)	L117P	probably damaging	Het
Phc2	T	C	4: 128,705,202 (GRCm38)	Y51H	probably damaging	Het
Ppp2r5b	A	G	19: 6,234,683 (GRCm38)	F50S	probably benign	Het
Prpf4b	A	G	13: 34,899,842 (GRCm38)	S865G	probably benign	Het
Ptpn5	C	T	7: 47,088,606 (GRCm38)	V243M	probably benign	Het
Rora	T	C	9: 69,364,559 (GRCm38)	L273P	possibly damaging	Het
Rtp4	T	A	16: 23,613,454 (GRCm38)	S245R	probably benign	Het
Scgb2b20	C	T	7: 33,364,560 (GRCm38)	G95D	probably benign	Het
Sec24b	A	G	3: 129,994,391 (GRCm38)	V820A	probably benign	Het
Sim2	A	G	16: 94,094,309 (GRCm38)	D62G	possibly damaging	Het
Slc17a4	A	T	13: 23,900,514 (GRCm38)	V429D	probably benign	Het
Sp2	T	C	11: 96,961,973 (GRCm38)	T42A	probably damaging	Het
Spata3	G	A	1: 86,024,447 (GRCm38)	R141Q	unknown	Het
Sptbn2	A	T	19: 4,745,577 (GRCm38)	E1658D	probably benign	Het
Tcaf1	T	C	6: 42,678,539 (GRCm38)	H501R	probably benign	Het
Tec	G	A	5: 72,773,835 (GRCm38)	T262M	possibly damaging	Het
Timm9	A	T	12: 71,125,531 (GRCm38)	N22K	possibly damaging	Het
Tln1	C	T	4: 43,542,701 (GRCm38)		probably null	Het
Tmbim4	A	G	10: 120,217,624 (GRCm38)	I109M	probably benign	Het
Tmc7	T	C	7: 118,564,343 (GRCm38)	K110E	probably benign	Het
Tmem107	C	T	11: 69,072,573 (GRCm38)	P136L	probably benign	Het
Ttc21b	T	C	2: 66,231,219 (GRCm38)		probably null	Het
Ubd	A	C	17: 37,195,444 (GRCm38)	T74P	probably damaging	Het
Vps11	A	G	9: 44,358,189 (GRCm38)	V255A	possibly damaging	Het
Vsnl1	T	C	12: 11,326,447 (GRCm38)	T146A	probably benign	Het
Wdr38	G	T	2: 38,999,972 (GRCm38)		probably null	Het
Yes1	T	A	5: 32,684,625 (GRCm38)	S498T	possibly damaging	Het
Zc3h13	G	A	14: 75,331,883 (GRCm38)	R1390H	probably damaging	Het
Zscan4b	A	G	7: 10,902,022 (GRCm38)	V126A	possibly 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
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
R5377:Lepr	UTSW	4	101,815,019 (GRCm38)	missense	possibly damaging	0.71
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'- TTTAGCACTGGACTGGGCAG -3'
(R):5'- AAGGCTTCTGCACAGACCAC -3'

Sequencing Primer
(F):5'- AGTTCCTGGCCTGGTCTAAC -3'
(R):5'- TAAATAAGTTGACTGGGAGGGTC -3'

Posted On

2019-06-07