Mutagenetix > Incidental Mutation

Incidental Mutation 'R4635:Nr1h2'

349438

Institutional Source

Beutler Lab

Gene Symbol

Nr1h2

Ensembl Gene

ENSMUSG00000060601

Gene Name

nuclear receptor subfamily 1, group H, member 2

Synonyms

Unr2, LXRB, RIP15, LXRbeta

MMRRC Submission

041899-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.632) question?

Stock #

R4635 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

44199040-44203375 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to C at 44201961 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Alanine at position 42 (S42A)

Ref Sequence

ENSEMBL: ENSMUSP00000146517 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000049343] [ENSMUST00000073488] [ENSMUST00000107910] [ENSMUST00000107911] [ENSMUST00000107912] [ENSMUST00000128600] [ENSMUST00000167197] [ENSMUST00000208366] [ENSMUST00000207737] [ENSMUST00000142298] [ENSMUST00000145956] [ENSMUST00000151793] [ENSMUST00000209017]

AlphaFold

Q60644

Predicted Effect

probably benign
Transcript: ENSMUST00000049343

SMART Domains

Protein: ENSMUSP00000039776
Gene: ENSMUSG00000038644

Domain	Start	End	E-Value	Type
coiled coil region	34	58	N/A	INTRINSIC
Blast:POLBc	65	108	1e-7	BLAST
low complexity region	212	225	N/A	INTRINSIC
Blast:POLBc	227	279	1e-19	BLAST
POLBc	306	763	2.53e-161	SMART
Blast:POLBc	790	837	1e-18	BLAST
Pfam:zf-C4pol	1010	1080	5.1e-22	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000073488
AA Change: S42A

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000073188
Gene: ENSMUSG00000060601
AA Change: S42A

Domain	Start	End	E-Value	Type
low complexity region	17	28	N/A	INTRINSIC
low complexity region	55	66	N/A	INTRINSIC
ZnF_C4	75	148	5.81e-32	SMART
low complexity region	153	188	N/A	INTRINSIC
low complexity region	190	202	N/A	INTRINSIC
HOLI	258	417	2.08e-42	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000107910
AA Change: S42A

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000103543
Gene: ENSMUSG00000060601
AA Change: S42A

Domain	Start	End	E-Value	Type
low complexity region	17	28	N/A	INTRINSIC
low complexity region	52	63	N/A	INTRINSIC
ZnF_C4	72	145	5.81e-32	SMART
low complexity region	150	185	N/A	INTRINSIC
low complexity region	187	199	N/A	INTRINSIC
HOLI	255	414	2.08e-42	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000107911
AA Change: S42A

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000103544
Gene: ENSMUSG00000060601
AA Change: S42A

Domain	Start	End	E-Value	Type
low complexity region	17	28	N/A	INTRINSIC
low complexity region	52	63	N/A	INTRINSIC
ZnF_C4	72	145	5.81e-32	SMART
low complexity region	150	185	N/A	INTRINSIC
low complexity region	187	199	N/A	INTRINSIC
HOLI	255	414	2.08e-42	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000107912
AA Change: S42A

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000103545
Gene: ENSMUSG00000060601
AA Change: S42A

Domain	Start	End	E-Value	Type
low complexity region	17	28	N/A	INTRINSIC
low complexity region	55	66	N/A	INTRINSIC
ZnF_C4	75	148	5.81e-32	SMART
low complexity region	153	188	N/A	INTRINSIC
low complexity region	190	202	N/A	INTRINSIC
HOLI	258	417	2.08e-42	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000123358

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000128354

Predicted Effect

probably benign
Transcript: ENSMUST00000128600
AA Change: S42A

PolyPhen 2 Score 0.271 (Sensitivity: 0.91; Specificity: 0.88)

Predicted Effect

probably benign
Transcript: ENSMUST00000167197
AA Change: S42A

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000126788
Gene: ENSMUSG00000060601
AA Change: S42A

Domain	Start	End	E-Value	Type
low complexity region	17	28	N/A	INTRINSIC
low complexity region	55	66	N/A	INTRINSIC
ZnF_C4	75	148	5.81e-32	SMART
low complexity region	153	188	N/A	INTRINSIC
low complexity region	190	202	N/A	INTRINSIC
HOLI	258	417	2.08e-42	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000132769

Predicted Effect

probably benign
Transcript: ENSMUST00000208366
AA Change: S42A

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

Predicted Effect

silent
Transcript: ENSMUST00000207737

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000207550

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000136611

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000141901

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000138746

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000137674

Predicted Effect

probably benign
Transcript: ENSMUST00000208322

Predicted Effect

probably benign
Transcript: ENSMUST00000142298

Predicted Effect

probably benign
Transcript: ENSMUST00000145956

SMART Domains

Protein: ENSMUSP00000117844
Gene: ENSMUSG00000038644

Domain	Start	End	E-Value	Type
coiled coil region	34	58	N/A	INTRINSIC
Blast:POLBc	65	108	2e-8	BLAST
PDB:3IAY\|A	76	151	7e-8	PDB
SCOP:d1tgoa1	117	153	3e-10	SMART
Blast:POLBc	130	153	7e-7	BLAST

Predicted Effect

probably benign
Transcript: ENSMUST00000151793

SMART Domains

Protein: ENSMUSP00000117157
Gene: ENSMUSG00000038644

Domain	Start	End	E-Value	Type
coiled coil region	34	58	N/A	INTRINSIC
Blast:POLBc	66	108	1e-7	BLAST
low complexity region	212	225	N/A	INTRINSIC
Blast:POLBc	227	279	1e-19	BLAST
POLBc	306	763	7.8e-164	SMART
Blast:POLBc	790	837	1e-18	BLAST
low complexity region	914	938	N/A	INTRINSIC
low complexity region	959	980	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000209017

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.2%
20x: 95.1%

Validation Efficiency

98% (39/40)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The liver X receptors, LXRA (NR1H3; MIM 602423) and LXRB, form a subfamily of the nuclear receptor superfamily and are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. The inducible LXRA is highly expressed in liver, adrenal gland, intestine, adipose tissue, macrophages, lung, and kidney, whereas LXRB is ubiquitously expressed. Ligand-activated LXRs form obligate heterodimers with retinoid X receptors (RXRs; see MIM 180245) and regulate expression of target genes containing LXR response elements (summary by Korf et al., 2009 [PubMed 19436111]).[supplied by OMIM, Jan 2010]
PHENOTYPE: Homozygous null mutations cause altered lipid, cholesterol and glucose metabolism and may lead to elevated cartilage matrix catabolism and PGE2 production, lipid-laden uterus myocytes and Sertoli cells, impaired uterus contractility and parturition, and higher susceptibility to bacterial infection. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 35 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb1a	A	T	5: 8,764,927 (GRCm39)	K639I	probably benign	Het
Amer3	C	A	1: 34,626,958 (GRCm39)	T399K	probably damaging	Het
Arfgef3	T	C	10: 18,510,603 (GRCm39)	Y786C	probably damaging	Het
Arhgef26	A	G	3: 62,247,861 (GRCm39)	Y315C	probably damaging	Het
Ccdc121	G	A	5: 31,645,435 (GRCm39)	R396Q	probably benign	Het
Chchd6	T	C	6: 89,444,448 (GRCm39)	E178G	probably damaging	Het
Chd3	TGCTGCCGCTGCCGC	TGCTGCCGCTGCCGCTGCCGC	11: 69,253,013 (GRCm39)		probably benign	Het
Daam1	T	A	12: 72,005,518 (GRCm39)		probably null	Het
Ddx60	A	G	8: 62,490,101 (GRCm39)	E1690G	probably benign	Het
Eme2	G	T	17: 25,113,882 (GRCm39)	P48T	probably benign	Het
Ferd3l	T	C	12: 33,978,835 (GRCm39)	M116T	probably damaging	Het
Gm13141	GGTTTCTTGATGCCA	G	4: 147,612,561 (GRCm39)		noncoding transcript	Het
Gtf2i	T	C	5: 134,274,028 (GRCm39)	N727D	probably damaging	Het
Hao1	T	A	2: 134,365,072 (GRCm39)	N185I	probably damaging	Het
Kifap3	C	T	1: 163,642,004 (GRCm39)	T195I	probably damaging	Het
Mag	A	G	7: 30,606,348 (GRCm39)	F363S	probably damaging	Het
Mef2a	A	G	7: 66,890,175 (GRCm39)	I135T	possibly damaging	Het
Muc4	T	C	16: 32,753,802 (GRCm38)	I1226T	probably benign	Het
Nphs1	T	C	7: 30,167,432 (GRCm39)	F787L	probably benign	Het
Odad4	C	T	11: 100,442,333 (GRCm39)	Q164*	probably null	Het
Or10ag2	T	A	2: 87,249,043 (GRCm39)	M217K	probably benign	Het
Or4a76	A	C	2: 89,460,516 (GRCm39)	I242S	possibly damaging	Het
Or51aa2	T	C	7: 103,188,355 (GRCm39)	I29V	probably benign	Het
Or5ak23	T	A	2: 85,245,208 (GRCm39)	N5I	probably damaging	Het
Rab38	T	C	7: 88,099,854 (GRCm39)	V123A	probably damaging	Het
Scd1	T	C	19: 44,395,024 (GRCm39)	Y67C	probably damaging	Het
Scn5a	T	C	9: 119,358,051 (GRCm39)	N730S	possibly damaging	Het
Shc2	C	T	10: 79,462,120 (GRCm39)	C341Y	probably benign	Het
Tfdp2	T	A	9: 96,179,727 (GRCm39)	N113K	probably damaging	Het
Tmc3	A	G	7: 83,234,290 (GRCm39)		probably benign	Het
Top6bl	A	G	19: 4,748,524 (GRCm39)		probably benign	Het
Tox	A	T	4: 6,990,501 (GRCm39)		probably benign	Het
Tspoap1	A	G	11: 87,668,683 (GRCm39)	K1319E	probably benign	Het
Vit	G	A	17: 78,881,641 (GRCm39)	V135I	probably benign	Het
Vwa5b1	T	G	4: 138,338,150 (GRCm39)	S71R	possibly damaging	Het

Other mutations in Nr1h2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02211:Nr1h2	APN	7	44,199,884 (GRCm39)	missense	probably damaging	1.00
IGL02327:Nr1h2	APN	7	44,200,924 (GRCm39)	unclassified	probably benign
bisogno	UTSW	7	44,199,437 (GRCm39)	missense	probably damaging	1.00
pickens	UTSW	7	44,199,746 (GRCm39)	missense	possibly damaging	0.65
quiero	UTSW	7	44,201,961 (GRCm39)	missense	probably benign	0.27
R0179:Nr1h2	UTSW	7	44,201,689 (GRCm39)	splice site	probably null
R0433:Nr1h2	UTSW	7	44,199,411 (GRCm39)	makesense	probably null
R0597:Nr1h2	UTSW	7	44,201,684 (GRCm39)	intron	probably benign
R2432:Nr1h2	UTSW	7	44,200,791 (GRCm39)	missense	possibly damaging	0.46
R4662:Nr1h2	UTSW	7	44,199,855 (GRCm39)	missense	probably damaging	1.00
R4675:Nr1h2	UTSW	7	44,201,979 (GRCm39)	missense	possibly damaging	0.66
R4782:Nr1h2	UTSW	7	44,199,923 (GRCm39)	missense	possibly damaging	0.93
R5064:Nr1h2	UTSW	7	44,201,073 (GRCm39)	missense	possibly damaging	0.82
R5191:Nr1h2	UTSW	7	44,199,840 (GRCm39)	missense	probably damaging	1.00
R6266:Nr1h2	UTSW	7	44,201,476 (GRCm39)	nonsense	probably null
R6933:Nr1h2	UTSW	7	44,199,437 (GRCm39)	missense	probably damaging	1.00
R7323:Nr1h2	UTSW	7	44,199,746 (GRCm39)	missense	possibly damaging	0.65
R7577:Nr1h2	UTSW	7	44,200,216 (GRCm39)	missense	probably damaging	1.00
R8099:Nr1h2	UTSW	7	44,199,746 (GRCm39)	missense	possibly damaging	0.65
R8431:Nr1h2	UTSW	7	44,199,767 (GRCm39)	missense	probably damaging	1.00
R8754:Nr1h2	UTSW	7	44,200,768 (GRCm39)	missense	probably damaging	0.98
R8962:Nr1h2	UTSW	7	44,201,463 (GRCm39)	missense	probably benign	0.01
R9079:Nr1h2	UTSW	7	44,199,430 (GRCm39)	missense	possibly damaging	0.94
Z1177:Nr1h2	UTSW	7	44,200,877 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CCAAGGGAAAGATCTGCAGGTC -3'
(R):5'- CTGCTTCGTGACCCACTATG -3'

Sequencing Primer
(F):5'- AAGATCTGCAGGTCGGCGG -3'
(R):5'- AAGTTCTCTGGACACTCCCGTG -3'

Posted On

2015-10-08