Mutagenetix > Incidental Mutation

Incidental Mutation 'R7073:Nr3c1'

549072

Institutional Source

Beutler Lab

Gene Symbol

Nr3c1

Ensembl Gene

ENSMUSG00000024431

Gene Name

nuclear receptor subfamily 3, group C, member 1

Synonyms

glucocorticoid receptor, Grl1, Grl-1, GR

MMRRC Submission

045169-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7073 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

39543598-39652474 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 39619449 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glutamic Acid at position 279 (D279E)

Ref Sequence

ENSEMBL: ENSMUSP00000095199 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000025300] [ENSMUST00000097592] [ENSMUST00000115567] [ENSMUST00000115571] [ENSMUST00000124115] [ENSMUST00000131885] [ENSMUST00000150483] [ENSMUST00000152853]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000025300
AA Change: D279E

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000025300
Gene: ENSMUSG00000024431
AA Change: D279E

Domain	Start	End	E-Value	Type
Pfam:GCR	27	418	1.4e-166	PFAM
ZnF_C4	434	505	7.6e-36	SMART
HOLI	580	744	8.8e-32	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000097592
AA Change: D279E

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000095199
Gene: ENSMUSG00000024431
AA Change: D279E

Domain	Start	End	E-Value	Type
Pfam:GCR	27	86	9.2e-16	PFAM
Pfam:GCR	75	418	1.4e-161	PFAM
ZnF_C4	434	506	8.6e-35	SMART
HOLI	581	745	8.8e-32	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000115567
AA Change: D279E

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000111229
Gene: ENSMUSG00000024431
AA Change: D279E

Domain	Start	End	E-Value	Type
Pfam:GCR	27	418	1.4e-166	PFAM
ZnF_C4	434	505	7.6e-36	SMART
HOLI	580	744	8.8e-32	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000115571
AA Change: D279E

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000111233
Gene: ENSMUSG00000024431
AA Change: D279E

Domain	Start	End	E-Value	Type
Pfam:GCR	27	418	1.4e-166	PFAM
ZnF_C4	434	505	7.6e-36	SMART
HOLI	580	744	8.8e-32	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000124115

SMART Domains

Protein: ENSMUSP00000119630
Gene: ENSMUSG00000024431

Domain	Start	End	E-Value	Type
Pfam:GCR	27	130	1e-27	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000131885

Predicted Effect

probably benign
Transcript: ENSMUST00000150483

Predicted Effect

probably benign
Transcript: ENSMUST00000152853
AA Change: D279E

PolyPhen 2 Score 0.028 (Sensitivity: 0.95; Specificity: 0.81)

SMART Domains

Protein: ENSMUSP00000120082
Gene: ENSMUSG00000024431
AA Change: D279E

Domain	Start	End	E-Value	Type
Pfam:GCR	27	418	5.7e-167	PFAM
ZnF_C4	434	488	5.65e-12	SMART

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.0%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes glucocorticoid receptor, which can function both as a transcription factor that binds to glucocorticoid response elements in the promoters of glucocorticoid responsive genes to activate their transcription, and as a regulator of other transcription factors. This receptor is typically found in the cytoplasm, but upon ligand binding, is transported into the nucleus. It is involved in inflammatory responses, cellular proliferation, and differentiation in target tissues. Mutations in this gene are associated with generalized glucocorticoid resistance. Alternative splicing of this gene results in transcript variants encoding either the same or different isoforms. Additional isoforms resulting from the use of alternate in-frame translation initiation sites have also been described, and shown to be functional, displaying diverse cytoplasm-to-nucleus trafficking patterns and distinct transcriptional activities (PMID:15866175). [provided by RefSeq, Feb 2011]
PHENOTYPE: Homozygous null mutants die at birth of respiratory failure with underdeveloped lungs, enlarged adrenals, elevated serum corticosterone and ACTH, and failed adrenaline synthesis. Mice with a point mutation have impaired gluconeogenesis and erythropoiesis. [provided by MGI curators]

Allele List at MGI

All alleles(12) : Targeted, knock-out(3) Targeted, other(8) Gene trapped(1)

Other mutations in this stock

Total: 80 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adgrv1	T	G	13: 81,709,593 (GRCm39)	E1133D	probably damaging	Het
Ankrd13b	A	T	11: 77,363,335 (GRCm39)	D505E	probably benign	Het
Ano1	C	T	7: 144,192,289 (GRCm39)	E361K	probably damaging	Het
Arap3	T	A	18: 38,107,495 (GRCm39)	K1341*	probably null	Het
Arhgef17	A	C	7: 100,579,198 (GRCm39)	Y583*	probably null	Het
Ash1l	G	A	3: 88,892,647 (GRCm39)	E1509K	probably damaging	Het
B430305J03Rik	T	G	3: 61,271,681 (GRCm39)	R21S	unknown	Het
Bbof1	A	G	12: 84,473,609 (GRCm39)	E313G	probably damaging	Het
Catsperb	C	T	12: 101,475,497 (GRCm39)	T347I	probably benign	Het
Ccdc24	G	T	4: 117,729,201 (GRCm39)	A92D	probably damaging	Het
Ccdc63	T	C	5: 122,249,073 (GRCm39)	T419A	probably benign	Het
Ccdc7a	C	T	8: 129,618,866 (GRCm39)	V893I	possibly damaging	Het
Ccdc88b	G	T	19: 6,831,330 (GRCm39)	D537E	probably benign	Het
Cd276	T	C	9: 58,444,615 (GRCm39)	S119G	probably damaging	Het
Cdkn3	T	C	14: 47,004,647 (GRCm39)	Y70H	possibly damaging	Het
Cdo1	G	A	18: 46,861,266 (GRCm39)		probably benign	Het
Cdr2	A	T	7: 120,581,247 (GRCm39)	F10Y	probably damaging	Het
Cep290	A	T	10: 100,374,865 (GRCm39)	K1370N	possibly damaging	Het
Crb1	T	A	1: 139,176,049 (GRCm39)	I645F	probably damaging	Het
Cul7	T	C	17: 46,969,657 (GRCm39)	W975R	probably damaging	Het
Ddx39b	A	C	17: 35,471,826 (GRCm39)	E324A	probably benign	Het
Diaph1	T	G	18: 38,022,867 (GRCm39)		probably null	Het
Dnah2	G	A	11: 69,321,318 (GRCm39)	R3917*	probably null	Het
Dnph1	T	A	17: 46,807,815 (GRCm39)	L27Q	probably damaging	Het
Duox2	A	G	2: 122,119,788 (GRCm39)	F880S	probably damaging	Het
Ell2	C	A	13: 75,910,006 (GRCm39)	L119M	probably damaging	Het
Enpep	A	T	3: 129,106,319 (GRCm39)	Y302*	probably null	Het
Ergic2	G	T	6: 148,096,707 (GRCm39)	H186Q	probably damaging	Het
Fam83b	T	C	9: 76,453,031 (GRCm39)	D12G	probably benign	Het
Fbxw16	A	T	9: 109,270,123 (GRCm39)	V206D	probably damaging	Het
Fhod1	A	T	8: 106,063,771 (GRCm39)	V278D	unknown	Het
Gba2	G	C	4: 43,573,753 (GRCm39)	Q180E	probably damaging	Het
Grhl3	G	A	4: 135,300,723 (GRCm39)	L5F	probably benign	Het
H2-T15	A	T	17: 36,369,235 (GRCm39)	C7S	unknown	Het
Ifit1bl1	C	T	19: 34,576,667 (GRCm39)		probably null	Het
Ift57	A	G	16: 49,584,230 (GRCm39)	T413A	probably benign	Het
Itga2	A	G	13: 114,996,149 (GRCm39)	F714S	probably damaging	Het
Jmy	A	G	13: 93,577,841 (GRCm39)	S776P	probably benign	Het
Kbtbd8	G	A	6: 95,098,814 (GRCm39)	A108T	probably damaging	Het
Kpna6	G	A	4: 129,548,139 (GRCm39)	A230V	probably damaging	Het
Lrfn1	C	T	7: 28,159,397 (GRCm39)	L439F	possibly damaging	Het
Lrrc1	T	A	9: 77,375,847 (GRCm39)	I147F	probably benign	Het
Lrrc7	C	T	3: 157,832,884 (GRCm39)	G1425R	probably damaging	Het
Madd	T	A	2: 90,992,854 (GRCm39)	I1022F	probably damaging	Het
Map2k2	A	T	10: 80,942,017 (GRCm39)	T13S	probably benign	Het
Mdc1	G	A	17: 36,164,960 (GRCm39)	V1459I	probably benign	Het
Mdh1b	G	A	1: 63,760,719 (GRCm39)	T114M	probably damaging	Het
Mfsd2a	T	C	4: 122,845,088 (GRCm39)	I208V	possibly damaging	Het
Mmrn1	T	A	6: 60,965,411 (GRCm39)	D1147E	probably damaging	Het
Nbeal2	T	A	9: 110,455,177 (GRCm39)	I2574F	probably damaging	Het
Nr1d1	T	G	11: 98,662,892 (GRCm39)	S34R	probably damaging	Het
Nrde2	T	C	12: 100,098,747 (GRCm39)	D640G	probably benign	Het
Odf4	A	G	11: 68,817,514 (GRCm39)	L58P	probably damaging	Het
Or4k41	A	T	2: 111,279,631 (GRCm39)	I49F	probably benign	Het
Or4p22	A	T	2: 88,317,651 (GRCm39)	I192F	probably benign	Het
Otud6b	A	C	4: 14,811,743 (GRCm39)	M300R	probably damaging	Het
Pamr1	T	A	2: 102,471,280 (GRCm39)	D534E	probably benign	Het
Pcdh7	T	A	5: 57,878,299 (GRCm39)	V618E	probably benign	Het
Pcgf6	A	C	19: 47,031,226 (GRCm39)	N266K	possibly damaging	Het
Plcz1	A	T	6: 139,968,849 (GRCm39)	Y196*	probably null	Het
Plxna1	A	T	6: 89,334,311 (GRCm39)	L106Q	probably damaging	Het
Qrich2	G	A	11: 116,337,701 (GRCm39)	A184V	probably damaging	Het
Rimkla	A	G	4: 119,325,275 (GRCm39)	L378S	probably benign	Het
Rufy1	G	T	11: 50,295,290 (GRCm39)	H472Q	probably benign	Het
Samd7	T	A	3: 30,810,631 (GRCm39)	M216K	probably benign	Het
Samd9l	A	T	6: 3,375,856 (GRCm39)	Y468*	probably null	Het
Scn2a	T	G	2: 65,558,787 (GRCm39)	L1194R	probably benign	Het
Sgo2a	T	A	1: 58,056,944 (GRCm39)	S1043T	possibly damaging	Het
Slc6a17	G	T	3: 107,378,755 (GRCm39)	H642Q	probably benign	Het
Smox	C	T	2: 131,364,031 (GRCm39)	A45V	possibly damaging	Het
St6galnac3	T	A	3: 153,117,274 (GRCm39)	T150S	possibly damaging	Het
Strip2	T	A	6: 29,941,911 (GRCm39)	I627N	possibly damaging	Het
Sv2c	A	T	13: 96,224,758 (GRCm39)	C184S	probably damaging	Het
Tm7sf2	A	T	19: 6,116,527 (GRCm39)		probably null	Het
Ttc28	T	C	5: 111,371,282 (GRCm39)	I608T	possibly damaging	Het
Vmn1r183	T	G	7: 23,754,926 (GRCm39)	L243R	probably damaging	Het
Vmn1r68	T	C	7: 10,261,778 (GRCm39)	T107A	probably benign	Het
Vnn3	G	A	10: 23,740,311 (GRCm39)	G205R	probably damaging	Het
Zfp516	T	A	18: 83,006,325 (GRCm39)		probably null	Het
Zpbp2	A	G	11: 98,443,335 (GRCm39)	D56G	probably damaging	Het

Other mutations in Nr3c1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00094:Nr3c1	APN	18	39,561,661 (GRCm39)	splice site	probably null
IGL00798:Nr3c1	APN	18	39,619,924 (GRCm39)	missense	probably damaging	1.00
IGL01527:Nr3c1	APN	18	39,619,690 (GRCm39)	missense	probably benign	0.00
IGL02088:Nr3c1	APN	18	39,557,444 (GRCm39)	missense	probably damaging	1.00
IGL02244:Nr3c1	APN	18	39,554,610 (GRCm39)	unclassified	probably benign
IGL03145:Nr3c1	APN	18	39,619,313 (GRCm39)	missense	probably damaging	1.00
IGL03236:Nr3c1	APN	18	39,619,444 (GRCm39)	missense	probably benign	0.00
3-1:Nr3c1	UTSW	18	39,619,092 (GRCm39)	missense	probably benign
R1296:Nr3c1	UTSW	18	39,620,051 (GRCm39)	nonsense	probably null
R2251:Nr3c1	UTSW	18	39,619,804 (GRCm39)	missense	probably benign	0.38
R2253:Nr3c1	UTSW	18	39,619,804 (GRCm39)	missense	probably benign	0.38
R2922:Nr3c1	UTSW	18	39,620,156 (GRCm39)	missense	possibly damaging	0.93
R4667:Nr3c1	UTSW	18	39,561,780 (GRCm39)	missense	probably benign	0.22
R4971:Nr3c1	UTSW	18	39,619,930 (GRCm39)	missense	probably damaging	1.00
R5106:Nr3c1	UTSW	18	39,619,654 (GRCm39)	missense	possibly damaging	0.80
R5732:Nr3c1	UTSW	18	39,548,752 (GRCm39)	missense	probably damaging	1.00
R5939:Nr3c1	UTSW	18	39,553,706 (GRCm39)	missense	probably benign	0.26
R5976:Nr3c1	UTSW	18	39,554,602 (GRCm39)	missense	probably damaging	1.00
R6091:Nr3c1	UTSW	18	39,620,011 (GRCm39)	small deletion	probably benign
R6666:Nr3c1	UTSW	18	39,620,200 (GRCm39)	missense	probably damaging	1.00
R7286:Nr3c1	UTSW	18	39,619,513 (GRCm39)	small insertion	probably benign
R7289:Nr3c1	UTSW	18	39,555,786 (GRCm39)	missense	probably benign	0.03
R7289:Nr3c1	UTSW	18	39,547,654 (GRCm39)	missense	probably benign	0.37
R7334:Nr3c1	UTSW	18	39,620,090 (GRCm39)	missense	probably benign	0.00
R8550:Nr3c1	UTSW	18	39,619,842 (GRCm39)	missense	possibly damaging	0.60
R8767:Nr3c1	UTSW	18	39,619,387 (GRCm39)	missense	probably damaging	0.99
X0019:Nr3c1	UTSW	18	39,620,195 (GRCm39)	missense	probably damaging	0.96
X0062:Nr3c1	UTSW	18	39,561,845 (GRCm39)	splice site	probably null

Predicted Primers

PCR Primer
(F):5'- TCACGCCATGAACAGAAATGG -3'
(R):5'- CCTTTGACATCTTGCAGGATTTGG -3'

Sequencing Primer
(F):5'- CCATGAACAGAAATGGCAGAC -3'
(R):5'- GAGTTTTCTGCCGGGTCCC -3'

Posted On

2019-05-15