Mutagenetix > Incidental Mutation

Incidental Mutation 'R5381:Rara'

478136

Institutional Source

Beutler Lab

Gene Symbol

Rara

Ensembl Gene

ENSMUSG00000037992

Gene Name

retinoic acid receptor, alpha

Synonyms

RARalpha1, RAR alpha 1

MMRRC Submission

042956-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5381 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

98818644-98865768 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 98862410 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Methionine at position 270 (I270M)

Ref Sequence

ENSEMBL: ENSMUSP00000129791 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000068133] [ENSMUST00000107473] [ENSMUST00000107474] [ENSMUST00000107475] [ENSMUST00000164748]

AlphaFold

P11416

Predicted Effect

possibly damaging
Transcript: ENSMUST00000068133
AA Change: I270M

PolyPhen 2 Score 0.925 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000069744
Gene: ENSMUSG00000037992
AA Change: I270M

Domain	Start	End	E-Value	Type
low complexity region	19	30	N/A	INTRINSIC
low complexity region	65	80	N/A	INTRINSIC
ZnF_C4	85	156	7.53e-40	SMART
HOLI	230	388	1.22e-34	SMART
low complexity region	425	436	N/A	INTRINSIC
low complexity region	439	462	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000107473
AA Change: I267M

PolyPhen 2 Score 0.301 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000103097
Gene: ENSMUSG00000037992
AA Change: I267M

Domain	Start	End	E-Value	Type
low complexity region	54	77	N/A	INTRINSIC
ZnF_C4	82	153	7.53e-40	SMART
HOLI	227	385	1.22e-34	SMART
low complexity region	422	433	N/A	INTRINSIC
low complexity region	436	459	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000107474
AA Change: I270M

PolyPhen 2 Score 0.925 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000103098
Gene: ENSMUSG00000037992
AA Change: I270M

Domain	Start	End	E-Value	Type
low complexity region	19	30	N/A	INTRINSIC
low complexity region	65	80	N/A	INTRINSIC
ZnF_C4	85	156	7.53e-40	SMART
HOLI	230	388	1.22e-34	SMART
low complexity region	425	436	N/A	INTRINSIC
low complexity region	439	462	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000107475
AA Change: I270M

PolyPhen 2 Score 0.925 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000103099
Gene: ENSMUSG00000037992
AA Change: I270M

Domain	Start	End	E-Value	Type
low complexity region	19	30	N/A	INTRINSIC
low complexity region	65	80	N/A	INTRINSIC
ZnF_C4	85	156	7.53e-40	SMART
HOLI	230	388	1.22e-34	SMART
low complexity region	425	436	N/A	INTRINSIC
low complexity region	439	462	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000164748
AA Change: I270M

PolyPhen 2 Score 0.925 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000129791
Gene: ENSMUSG00000037992
AA Change: I270M

Domain	Start	End	E-Value	Type
low complexity region	19	30	N/A	INTRINSIC
low complexity region	65	80	N/A	INTRINSIC
ZnF_C4	85	156	7.53e-40	SMART
HOLI	230	388	1.22e-34	SMART
low complexity region	425	436	N/A	INTRINSIC
low complexity region	439	462	N/A	INTRINSIC

Meta Mutation Damage Score

0.1795

Coding Region Coverage

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

Validation Efficiency

100% (74/74)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene represents a nuclear retinoic acid receptor. The encoded protein, retinoic acid receptor alpha, regulates transcription in a ligand-dependent manner. This gene has been implicated in regulation of development, differentiation, apoptosis, granulopoeisis, and transcription of clock genes. Translocations between this locus and several other loci have been associated with acute promyelocytic leukemia. Alternatively spliced transcript variants have been found for this locus.[provided by RefSeq, Sep 2010]
PHENOTYPE: Homozygotes for targeted null mutations show high neonatal mortality due to maternal cannibalization, failure to thrive, and excess mortality during the postnatal period. Male survivors exhibit testicular degeneration. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 67 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700086D15Rik	G	T	11: 65,044,137 (GRCm39)	S19*	probably null	Het
4930432E11Rik	A	T	7: 29,262,393 (GRCm39)		noncoding transcript	Het
Acvr1c	T	C	2: 58,177,747 (GRCm39)	T241A	probably damaging	Het
Ankmy1	T	C	1: 92,804,284 (GRCm39)	T900A	probably benign	Het
Anp32a	A	C	9: 62,279,459 (GRCm39)	E107A	probably damaging	Het
Arhgef40	T	C	14: 52,229,306 (GRCm39)	I623T	probably damaging	Het
Camsap3	T	A	8: 3,653,812 (GRCm39)	I483N	probably damaging	Het
Card9	G	A	2: 26,248,895 (GRCm39)	L85F	probably damaging	Het
Cbfa2t2	T	G	2: 154,365,849 (GRCm39)	V353G	probably damaging	Het
Ccdc166	A	T	15: 75,852,701 (GRCm39)	L422*	probably null	Het
Ccdc198	T	C	14: 49,470,364 (GRCm39)	D185G	probably damaging	Het
Ccdc73	A	T	2: 104,820,270 (GRCm39)	N416Y	probably damaging	Het
Celsr2	A	T	3: 108,310,073 (GRCm39)	D1552E	probably damaging	Het
Ces1b	A	T	8: 93,791,647 (GRCm39)	N317K	probably benign	Het
Col6a3	T	C	1: 90,703,334 (GRCm39)	R2471G	unknown	Het
Crocc	C	T	4: 140,756,622 (GRCm39)	R1165H	possibly damaging	Het
Csmd3	T	A	15: 47,604,611 (GRCm39)	Y1955F	probably benign	Het
Ctbp1	A	T	5: 33,407,034 (GRCm39)	D232E	probably benign	Het
Cuedc1	T	A	11: 88,078,812 (GRCm39)		probably null	Het
Dctd	C	T	8: 48,590,449 (GRCm39)		probably benign	Het
Dusp6	G	A	10: 99,102,129 (GRCm39)	V226I	possibly damaging	Het
Gpr152	A	G	19: 4,192,516 (GRCm39)	E19G	probably damaging	Het
Ighv16-1	T	C	12: 114,032,593 (GRCm39)	T70A	probably benign	Het
Igkv4-80	A	C	6: 68,993,649 (GRCm39)	S81A	probably benign	Het
Il12b	C	A	11: 44,298,699 (GRCm39)	D51E	possibly damaging	Het
Il9r	T	G	11: 32,140,715 (GRCm39)	D435A	probably benign	Het
Jakmip2	T	C	18: 43,715,025 (GRCm39)	D167G	probably damaging	Het
Klrd1	A	G	6: 129,572,397 (GRCm39)	D63G	possibly damaging	Het
Lactb	A	G	9: 66,863,297 (GRCm39)	L439P	probably damaging	Het
Laptm5	T	C	4: 130,660,969 (GRCm39)		probably benign	Het
Lgals1	A	G	15: 78,814,223 (GRCm39)	D96G	probably benign	Het
Lrp8	A	T	4: 107,726,307 (GRCm39)	H871L	probably damaging	Het
Mfap4	A	T	11: 61,378,756 (GRCm39)	I235F	probably benign	Het
Muc6	G	A	7: 141,217,836 (GRCm39)	T2279I	possibly damaging	Het
Nlrp4b	T	A	7: 10,449,172 (GRCm39)	Y91*	probably null	Het
Osbp2	A	G	11: 3,655,593 (GRCm39)	Y383H	probably benign	Het
Otx1	C	A	11: 21,947,037 (GRCm39)	A91S	probably damaging	Het
Palb2	G	T	7: 121,727,636 (GRCm39)	T78K	probably benign	Het
Panx2	G	T	15: 88,944,433 (GRCm39)	V53L	probably damaging	Het
Pip4p1	T	C	14: 51,166,495 (GRCm39)	E161G	probably benign	Het
Pitx1	T	C	13: 55,973,892 (GRCm39)	Y313C	probably damaging	Het
Pjvk	A	G	2: 76,481,904 (GRCm39)		probably null	Het
Pnldc1	T	G	17: 13,109,283 (GRCm39)	K439T	probably benign	Het
Ppp4r4	A	C	12: 103,559,357 (GRCm39)	T513P	probably benign	Het
Pram1	A	T	17: 33,860,600 (GRCm39)	Q389L	probably damaging	Het
Prg4	T	C	1: 150,330,204 (GRCm39)		probably benign	Het
Prkch	C	A	12: 73,738,366 (GRCm39)	R158S	probably damaging	Het
Ptpn7	A	T	1: 135,070,906 (GRCm39)	M332L	probably damaging	Het
Rad51c	A	T	11: 87,288,459 (GRCm39)	D241E	probably benign	Het
Ryr2	T	A	13: 11,571,544 (GRCm39)	D4898V	probably damaging	Het
Sec31b	C	T	19: 44,522,810 (GRCm39)	G218S	probably damaging	Het
Slc9a1	T	A	4: 133,149,382 (GRCm39)	L736Q	probably damaging	Het
Slco2a1	A	T	9: 102,945,213 (GRCm39)	D196V	probably damaging	Het
Sp3	C	A	2: 72,800,910 (GRCm39)	A368S	probably benign	Het
Stk24	A	T	14: 121,531,645 (GRCm39)	L337Q	possibly damaging	Het
Tbc1d13	A	G	2: 30,027,379 (GRCm39)	T96A	probably benign	Het
Tm2d3	G	A	7: 65,351,420 (GRCm39)	G225S	probably damaging	Het
Urb2	T	C	8: 124,756,651 (GRCm39)	V786A	probably benign	Het
Usp32	C	T	11: 84,949,953 (GRCm39)		probably benign	Het
Usp54	C	T	14: 20,636,144 (GRCm39)	G300D	probably damaging	Het
Vmn1r124	T	A	7: 20,994,323 (GRCm39)	N74Y	probably damaging	Het
Vmn1r77	T	A	7: 11,775,952 (GRCm39)	C175S	probably damaging	Het
Vmn2r62	G	T	7: 42,437,219 (GRCm39)	Q422K	probably benign	Het
Vmn2r76	A	G	7: 85,874,496 (GRCm39)	F827S	probably damaging	Het
Vps52	A	G	17: 34,177,275 (GRCm39)	S106G	possibly damaging	Het
Zdhhc1	CGGGGG	CGGGGGG	8: 106,210,376 (GRCm39)		probably null	Het
Zic2	A	G	14: 122,713,227 (GRCm39)	N47S	probably damaging	Het

Other mutations in Rara

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00951:Rara	APN	11	98,858,992 (GRCm39)	missense	probably benign	0.00
IGL01155:Rara	APN	11	98,859,010 (GRCm39)	missense	possibly damaging	0.92
IGL02141:Rara	APN	11	98,858,907 (GRCm39)	missense	probably damaging	1.00
IGL03194:Rara	APN	11	98,862,490 (GRCm39)	missense	possibly damaging	0.96
annie	UTSW	11	98,864,452 (GRCm39)	missense	unknown
kane	UTSW	11	98,862,595 (GRCm39)	missense	probably damaging	1.00
Orphan	UTSW	11	98,860,989 (GRCm39)	missense	probably damaging	1.00
warbucks	UTSW	11	98,861,395 (GRCm39)	missense	probably damaging	1.00
PIT4486001:Rara	UTSW	11	98,864,321 (GRCm39)	missense	possibly damaging	0.88
R0626:Rara	UTSW	11	98,862,406 (GRCm39)	critical splice acceptor site	probably null
R1973:Rara	UTSW	11	98,862,496 (GRCm39)	missense	possibly damaging	0.91
R3975:Rara	UTSW	11	98,861,395 (GRCm39)	missense	probably damaging	1.00
R4357:Rara	UTSW	11	98,858,937 (GRCm39)	missense	probably damaging	0.98
R5102:Rara	UTSW	11	98,857,185 (GRCm39)	missense	possibly damaging	0.80
R5147:Rara	UTSW	11	98,841,550 (GRCm39)	missense	probably benign	0.35
R5570:Rara	UTSW	11	98,863,478 (GRCm39)	missense	probably damaging	1.00
R5861:Rara	UTSW	11	98,858,987 (GRCm39)	nonsense	probably null
R6273:Rara	UTSW	11	98,861,048 (GRCm39)	missense	probably benign	0.00
R6404:Rara	UTSW	11	98,851,839 (GRCm39)	missense	probably benign	0.16
R8906:Rara	UTSW	11	98,860,989 (GRCm39)	missense	probably damaging	1.00
R8921:Rara	UTSW	11	98,864,452 (GRCm39)	missense	unknown
R8978:Rara	UTSW	11	98,862,595 (GRCm39)	missense	probably damaging	1.00
R9224:Rara	UTSW	11	98,857,236 (GRCm39)	frame shift	probably null
R9476:Rara	UTSW	11	98,860,983 (GRCm39)	missense	probably benign	0.02
R9510:Rara	UTSW	11	98,860,983 (GRCm39)	missense	probably benign	0.02

Predicted Primers

PCR Primer
(F):5'- CTCTATACGAAGGCAGCGTG -3'
(R):5'- CAGTCTCAGCATCGTCCATC -3'

Sequencing Primer
(F):5'- TACAATTAGACTCAGTTCAGTCCC -3'
(R):5'- AGCATCGTCCATCTCCAGG -3'

Posted On

2017-05-26