Mutagenetix > Incidental Mutation

Incidental Mutation 'R7334:Nr3c1'

569401

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

045371-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7334 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

39543598-39652474 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 39620090 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Phenylalanine to Leucine at position 66 (F66L)

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: F66L

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000025300
Gene: ENSMUSG00000024431
AA Change: F66L

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: F66L

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000095199
Gene: ENSMUSG00000024431
AA Change: F66L

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: F66L

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000111229
Gene: ENSMUSG00000024431
AA Change: F66L

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: F66L

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000111233
Gene: ENSMUSG00000024431
AA Change: F66L

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
AA Change: F66L

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000119630
Gene: ENSMUSG00000024431
AA Change: F66L

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: F66L

PolyPhen 2 Score 0.030 (Sensitivity: 0.95; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000120082
Gene: ENSMUSG00000024431
AA Change: F66L

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

Meta Mutation Damage Score

0.0868

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.1%

Validation Efficiency

99% (75/76)

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: 74 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aadacl2fm3	T	A	3: 59,776,380 (GRCm39)	C184S	probably damaging	Het
Acadm	G	T	3: 153,644,698 (GRCm39)	S9*	probably null	Het
Acot10	C	T	15: 20,665,629 (GRCm39)	V371I	possibly damaging	Het
Adam8	T	C	7: 139,568,903 (GRCm39)	E199G	probably damaging	Het
Aldh18a1	A	T	19: 40,539,696 (GRCm39)	W762R	probably damaging	Het
Aldh1a1	T	A	19: 20,599,075 (GRCm39)	V162E	probably damaging	Het
Alms1	A	G	6: 85,618,432 (GRCm39)	D2357G	probably damaging	Het
Arfgef1	G	T	1: 10,254,685 (GRCm39)	Q718K	probably damaging	Het
Arid5b	A	C	10: 68,079,007 (GRCm39)	V110G	possibly damaging	Het
Bpifb3	T	A	2: 153,761,654 (GRCm39)	D34E	probably damaging	Het
Cacfd1	C	T	2: 26,905,558 (GRCm39)	A85V	possibly damaging	Het
Cep57l1	C	A	10: 41,597,596 (GRCm39)	S345I	probably benign	Het
Cibar2	T	C	8: 120,901,589 (GRCm39)	T39A	probably damaging	Het
Clca3b	G	A	3: 144,542,417 (GRCm39)	R462*	probably null	Het
Cyp26c1	G	A	19: 37,677,323 (GRCm39)	V251I	probably benign	Het
Dip2a	A	G	10: 76,110,080 (GRCm39)	S1179P	possibly damaging	Het
Dnal1	T	C	12: 84,173,780 (GRCm39)	L27P	probably damaging	Het
Dock7	A	G	4: 98,864,180 (GRCm39)	V1288A	unknown	Het
Elmod1	A	T	9: 53,841,508 (GRCm39)		probably null	Het
Epb41l5	T	G	1: 119,551,679 (GRCm39)	K102T	probably damaging	Het
Fermt3	T	C	19: 6,980,406 (GRCm39)	I358V	probably benign	Het
Frmd3	A	G	4: 74,079,955 (GRCm39)	I316V	probably benign	Het
Fryl	T	C	5: 73,204,839 (GRCm39)		probably null	Het
Gm4131	T	A	14: 62,702,356 (GRCm39)	H204L	possibly damaging	Het
Hmcn2	G	A	2: 31,325,806 (GRCm39)	G4278R	probably damaging	Het
Hmcn2	A	G	2: 31,343,147 (GRCm39)	S4558G	possibly damaging	Het
Igkv1-132	A	G	6: 67,737,108 (GRCm39)	T25A	probably benign	Het
Kcp	T	C	6: 29,485,511 (GRCm39)	E1161G	probably damaging	Het
Macf1	A	T	4: 123,293,235 (GRCm39)	I5371K	probably damaging	Het
Malrd1	T	A	2: 16,011,529 (GRCm39)	C1670S	probably damaging	Het
Mfsd13a	T	A	19: 46,356,809 (GRCm39)	V270E	probably damaging	Het
Mroh1	A	G	15: 76,311,838 (GRCm39)	I524V	probably benign	Het
Mta1	T	C	12: 113,090,418 (GRCm39)	S175P	possibly damaging	Het
Myo7a	C	T	7: 97,728,573 (GRCm39)	R800H	probably benign	Het
Ncald	T	A	15: 37,397,524 (GRCm39)	Y52F	probably damaging	Het
Nherf1	C	T	11: 115,054,593 (GRCm39)	A81V	possibly damaging	Het
Nomo1	T	C	7: 45,732,692 (GRCm39)	S1152P	probably damaging	Het
Nrf1	T	C	6: 30,118,970 (GRCm39)	L363S	probably benign	Het
Or4n4	C	A	14: 50,519,036 (GRCm39)	V225F	probably benign	Het
Or8b12b	A	T	9: 37,684,293 (GRCm39)	I113F	probably damaging	Het
Osbpl3	A	G	6: 50,321,886 (GRCm39)	M300T	possibly damaging	Het
Parpbp	T	A	10: 87,947,617 (GRCm39)	N339I	probably damaging	Het
Pdlim5	A	T	3: 141,950,678 (GRCm39)	H578Q	probably damaging	Het
Pear1	T	C	3: 87,657,532 (GRCm39)	N1009S	probably damaging	Het
Pnpla8	A	G	12: 44,358,286 (GRCm39)	I745M	probably damaging	Het
Pom121l12	C	A	11: 14,549,681 (GRCm39)	T129K	probably damaging	Het
Ppp1r14a	T	C	7: 28,992,687 (GRCm39)	S130P	probably damaging	Het
Prss12	A	C	3: 123,280,780 (GRCm39)	L488F	probably benign	Het
Psd3	C	T	8: 68,361,357 (GRCm39)	V559I	possibly damaging	Het
Rrh	T	C	3: 129,602,631 (GRCm39)	T364A	probably benign	Het
Shcbp1	A	T	8: 4,791,876 (GRCm39)	M479K	probably damaging	Het
Shcbp1	A	C	8: 4,804,310 (GRCm39)	F200C	probably damaging	Het
Slx1b	G	T	7: 126,291,699 (GRCm39)	R122S	probably damaging	Het
Spata31f1e	G	A	4: 42,793,856 (GRCm39)	T92I	possibly damaging	Het
Spidr	A	G	16: 15,932,689 (GRCm39)		probably null	Het
St18	G	A	1: 6,872,783 (GRCm39)	D173N	probably benign	Het
Stambpl1	T	C	19: 34,204,048 (GRCm39)	I46T	probably damaging	Het
Syne1	C	T	10: 5,007,886 (GRCm39)	D113N	probably damaging	Het
Tg	G	A	15: 66,597,121 (GRCm39)	V1741I	probably benign	Het
Thsd7b	T	A	1: 130,123,012 (GRCm39)	W1544R	probably benign	Het
Tiam2	G	A	17: 3,553,283 (GRCm39)	R1120H	possibly damaging	Het
Tinag	A	T	9: 76,908,931 (GRCm39)	C337S	probably damaging	Het
Tm4sf1	G	C	3: 57,200,510 (GRCm39)	A64G	probably damaging	Het
Tmprss6	A	G	15: 78,328,017 (GRCm39)	Y572H	unknown	Het
Tnfrsf11a	G	A	1: 105,754,854 (GRCm39)	A309T	possibly damaging	Het
Txndc11	A	G	16: 10,946,425 (GRCm39)	Y129H	probably damaging	Het
Ube3b	T	C	5: 114,553,742 (GRCm39)	F974S	possibly damaging	Het
Utrn	C	A	10: 12,603,753 (GRCm39)		probably null	Het
Vmn1r58	T	A	7: 5,414,066 (GRCm39)	M55L	probably benign	Het
Vnn1	T	A	10: 23,776,658 (GRCm39)	S336R	probably benign	Het
Wwc2	T	C	8: 48,322,829 (GRCm39)	Y424C	unknown	Het
Zfp507	T	C	7: 35,475,505 (GRCm39)	I903V	probably damaging	Het
Zfp551	C	T	7: 12,150,681 (GRCm39)	G243R	probably damaging	Het
Zfp60	T	A	7: 27,448,444 (GRCm39)	C371S	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
R7073:Nr3c1	UTSW	18	39,619,449 (GRCm39)	missense	probably benign	0.00
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
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'- CCGAAAGTCTGTTTCCCCAG -3'
(R):5'- GGACTCCAAAGAATCCTTAGCTC -3'

Sequencing Primer
(F):5'- AAGCTGGCCCTGCTGTG -3'
(R):5'- TTAGCTCCCCCTGGTAGAGAC -3'

Posted On

2019-09-13