Mutagenetix > Incidental Mutation

Incidental Mutation 'R0491:Fkbp4'

42465

Institutional Source

Beutler Lab

Gene Symbol

Fkbp4

Ensembl Gene

ENSMUSG00000030357

Gene Name

FK506 binding protein 4

Synonyms

FKBP-52, FKBP52

MMRRC Submission

038689-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.833) question?

Stock #

R0491 (G1)

Quality Score

186

Status

Validated

Chromosome

Chromosomal Location

128407066-128415619 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 128412705 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Threonine at position 75 (I75T)

Ref Sequence

ENSEMBL: ENSMUSP00000119930 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000032508] [ENSMUST00000150387] [ENSMUST00000151796]

AlphaFold

P30416

Predicted Effect

probably damaging
Transcript: ENSMUST00000032508
AA Change: I122T

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000032508
Gene: ENSMUSG00000030357
AA Change: I122T

Domain	Start	End	E-Value	Type
Pfam:FKBP_C	43	135	2.6e-33	PFAM
Pfam:FKBP_C	160	250	1.3e-14	PFAM
TPR	270	303	4.44e1	SMART
TPR	319	352	1.76e-5	SMART
TPR	353	386	2e-4	SMART
low complexity region	419	431	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000139448

SMART Domains

Protein: ENSMUSP00000114939
Gene: ENSMUSG00000030357

Domain	Start	End	E-Value	Type
Pfam:FKBP_C	43	135	3.8e-33	PFAM
Pfam:FKBP_C	160	250	2.5e-14	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000144745

Predicted Effect

probably damaging
Transcript: ENSMUST00000150387
AA Change: I75T

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000119930
Gene: ENSMUSG00000030357
AA Change: I75T

Domain	Start	End	E-Value	Type
Pfam:FKBP_C	1	88	7.8e-31	PFAM
Pfam:FKBP_C	113	203	4.7e-13	PFAM
Blast:TPR	223	256	3e-14	BLAST

Predicted Effect

probably damaging
Transcript: ENSMUST00000151796
AA Change: I75T

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000122087
Gene: ENSMUSG00000030357
AA Change: I75T

Domain	Start	End	E-Value	Type
Pfam:FKBP_C	1	88	3.7e-31	PFAM
Pfam:FKBP_C	113	187	3.2e-8	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000204081

Meta Mutation Damage Score

0.9427

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.8%
20x: 94.4%

Validation Efficiency

100% (65/65)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds to the immunosuppressants FK506 and rapamycin. It has high structural and functional similarity to FK506-binding protein 1A (FKBP1A), but unlike FKBP1A, this protein does not have immunosuppressant activity when complexed with FK506. It interacts with interferon regulatory factor-4 and plays an important role in immunoregulatory gene expression in B and T lymphocytes. This encoded protein is known to associate with phytanoyl-CoA alpha-hydroxylase. It can also associate with two heat shock proteins (hsp90 and hsp70) and thus may play a role in the intracellular trafficking of hetero-oligomeric forms of the steroid hormone receptors. This protein correlates strongly with adeno-associated virus type 2 vectors (AAV) resulting in a significant increase in AAV-mediated transgene expression in human cell lines. Thus this encoded protein is thought to have important implications for the optimal use of AAV vectors in human gene therapy. The human genome contains several non-transcribed pseudogenes similar to this gene. [provided by RefSeq, Sep 2008]
PHENOTYPE: Homozygous null males show reproductive tissue defects consistent with androgen insensitivity such as ambiguous external genitalia, dysgenic prostate, malformed seminal gland and cryptorchism. Males also exhibit hypospadia and infertility. Females are sterile due to failure of implantation. [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
Abca13	T	C	11: 9,248,235 (GRCm39)	F2661L	probably benign	Het
Acadsb	A	G	7: 131,031,836 (GRCm39)	D224G	probably benign	Het
Acsm1	A	G	7: 119,239,920 (GRCm39)	H288R	probably damaging	Het
Adamts2	A	G	11: 50,667,457 (GRCm39)	D465G	probably damaging	Het
Akap9	A	T	5: 4,022,851 (GRCm39)		probably benign	Het
Alms1	A	G	6: 85,679,582 (GRCm39)	T3240A	probably damaging	Het
Ap3d1	A	G	10: 80,555,075 (GRCm39)	W417R	probably damaging	Het
Arfgef1	C	A	1: 10,250,212 (GRCm39)		probably benign	Het
Atf6	A	G	1: 170,614,913 (GRCm39)		probably null	Het
Cacna1s	T	A	1: 136,016,746 (GRCm39)		probably benign	Het
Clcn1	T	C	6: 42,287,515 (GRCm39)	F740L	probably benign	Het
Clec12a	T	A	6: 129,341,016 (GRCm39)	D265E	probably benign	Het
Clic3	T	A	2: 25,347,797 (GRCm39)		probably benign	Het
Cntnap3	T	G	13: 64,909,859 (GRCm39)	T749P	probably benign	Het
Col11a2	T	A	17: 34,261,186 (GRCm39)	D45E	probably null	Het
Cplane1	T	A	15: 8,211,727 (GRCm39)	S356T	probably damaging	Het
Crxos	T	A	7: 15,632,460 (GRCm39)	S89T	probably benign	Het
Cxcr1	G	T	1: 74,231,468 (GRCm39)	P185T	possibly damaging	Het
Cyp20a1	T	A	1: 60,410,486 (GRCm39)	N262K	possibly damaging	Het
Dennd2b	T	A	7: 109,156,411 (GRCm39)	Q113L	probably benign	Het
Dpy19l2	T	C	9: 24,607,324 (GRCm39)	R46G	probably benign	Het
Dpysl2	A	T	14: 67,045,411 (GRCm39)	L454Q	probably damaging	Het
Dvl3	C	T	16: 20,346,173 (GRCm39)		probably benign	Het
Eppin	T	A	2: 164,431,332 (GRCm39)	E98V	possibly damaging	Het
Fancm	A	T	12: 65,152,835 (GRCm39)	H1097L	probably benign	Het
Fmn2	A	G	1: 174,409,525 (GRCm39)	H586R	unknown	Het
Gm973	C	T	1: 59,597,393 (GRCm39)		probably benign	Het
Haus6	A	C	4: 86,521,083 (GRCm39)	V185G	possibly damaging	Het
Herc2	T	A	7: 55,772,114 (GRCm39)	C1098S	possibly damaging	Het
Hic1	C	A	11: 75,057,136 (GRCm39)	L584F	possibly damaging	Het
Itgb1bp1	C	A	12: 21,326,896 (GRCm39)		probably benign	Het
Kbtbd2	G	A	6: 56,757,374 (GRCm39)	R121*	probably null	Het
Lgr4	C	T	2: 109,837,626 (GRCm39)		probably benign	Het
Lrrc55	T	C	2: 85,022,264 (GRCm39)	E309G	probably damaging	Het
Mertk	T	C	2: 128,635,027 (GRCm39)		probably null	Het
Micu3	A	G	8: 40,819,294 (GRCm39)		probably benign	Het
Mmp11	G	A	10: 75,762,592 (GRCm39)	A287V	probably benign	Het
Mpzl2	A	G	9: 44,954,039 (GRCm39)	Y47C	probably damaging	Het
Muc5b	A	C	7: 141,415,752 (GRCm39)	R2899S	probably benign	Het
Myo1b	A	G	1: 51,794,857 (GRCm39)	Y1078H	probably benign	Het
Naip1	A	T	13: 100,559,727 (GRCm39)	D1092E	probably benign	Het
Ncapd3	T	G	9: 26,969,179 (GRCm39)	V611G	probably damaging	Het
Ntpcr	C	T	8: 126,464,093 (GRCm39)	R73*	probably null	Het
Or4c120	A	T	2: 89,000,704 (GRCm39)	V284E	probably benign	Het
Or5b119	G	A	19: 13,456,857 (GRCm39)	A235V	probably damaging	Het
Osbp2	A	G	11: 3,664,709 (GRCm39)	F88S	probably damaging	Het
Pkn3	A	T	2: 29,979,889 (GRCm39)	T711S	probably damaging	Het
Plekhm1	T	C	11: 103,285,602 (GRCm39)	K278E	probably benign	Het
Ppp1r36	A	G	12: 76,486,065 (GRCm39)	T408A	probably benign	Het
Prss41	T	C	17: 24,061,477 (GRCm39)	T105A	possibly damaging	Het
Psme1	G	T	14: 55,817,378 (GRCm39)		probably benign	Het
Ptprq	A	T	10: 107,444,036 (GRCm39)	Y1523N	probably damaging	Het
Ric8b	A	G	10: 84,828,086 (GRCm39)	D470G	probably damaging	Het
Scarb1	A	G	5: 125,375,795 (GRCm39)		probably benign	Het
Slc25a54	G	A	3: 109,010,112 (GRCm39)	A204T	probably damaging	Het
Spink10	T	C	18: 62,793,036 (GRCm39)	C67R	probably damaging	Het
Tmtc1	A	T	6: 148,314,138 (GRCm39)		probably null	Het
Tprkb	A	G	6: 85,901,446 (GRCm39)	D28G	probably benign	Het
Ttll13	A	G	7: 79,910,098 (GRCm39)	H747R	probably benign	Het
Usp24	A	G	4: 106,259,302 (GRCm39)	S1608G	probably benign	Het
Utp20	A	T	10: 88,596,774 (GRCm39)	F2115L	probably damaging	Het
Vmn1r200	A	T	13: 22,579,361 (GRCm39)	I46L	probably benign	Het
Zdhhc8	A	T	16: 18,046,254 (GRCm39)	M103K	probably damaging	Het
Zfp595	C	T	13: 67,465,369 (GRCm39)	G298E	probably damaging	Het
Zfp738	T	G	13: 67,818,140 (GRCm39)	H617P	possibly damaging	Het
Zfp9	A	T	6: 118,442,163 (GRCm39)	H166Q	probably damaging	Het
Zp3r	C	A	1: 130,546,071 (GRCm39)	D80Y	probably damaging	Het

Other mutations in Fkbp4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01151:Fkbp4	APN	6	128,412,754 (GRCm39)	missense	probably benign	0.28
IGL02215:Fkbp4	APN	6	128,411,433 (GRCm39)	splice site	probably benign
IGL02607:Fkbp4	APN	6	128,411,433 (GRCm39)	splice site	probably benign
IGL03186:Fkbp4	APN	6	128,411,763 (GRCm39)	missense	probably benign
IGL03238:Fkbp4	APN	6	128,411,720 (GRCm39)	missense	probably damaging	1.00
R0083:Fkbp4	UTSW	6	128,409,370 (GRCm39)	unclassified	probably benign
R1652:Fkbp4	UTSW	6	128,413,637 (GRCm39)	missense	probably damaging	0.97
R1868:Fkbp4	UTSW	6	128,409,453 (GRCm39)	missense	probably benign	0.00
R2010:Fkbp4	UTSW	6	128,412,765 (GRCm39)	missense	probably benign	0.01
R2292:Fkbp4	UTSW	6	128,413,625 (GRCm39)	missense	probably damaging	1.00
R5616:Fkbp4	UTSW	6	128,410,517 (GRCm39)	missense	probably damaging	0.99
R6478:Fkbp4	UTSW	6	128,410,194 (GRCm39)	missense	probably damaging	1.00
R7156:Fkbp4	UTSW	6	128,412,787 (GRCm39)	missense	probably benign	0.31
R9182:Fkbp4	UTSW	6	128,415,382 (GRCm39)	missense	probably benign
R9445:Fkbp4	UTSW	6	128,413,580 (GRCm39)	missense	probably damaging	1.00
R9739:Fkbp4	UTSW	6	128,410,728 (GRCm39)	missense	probably benign	0.00
Z1177:Fkbp4	UTSW	6	128,410,074 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GCAGAGCCAGTTAACCTTTCCACC -3'
(R):5'- TAAGAACAACACCGCCCTGCTTGTC -3'

Sequencing Primer
(F):5'- CTTACCTCCTACTAAAGCTAGGC -3'
(R):5'- TCTAGAGGTGTTCAGATTCTGC -3'

Posted On

2013-05-23