Mutagenetix > Incidental Mutation

Incidental Mutation 'R6478:Fkbp4'

516905

Institutional Source

Beutler Lab

Gene Symbol

Fkbp4

Ensembl Gene

ENSMUSG00000030357

Gene Name

FK506 binding protein 4

Synonyms

FKBP-52, FKBP52

MMRRC Submission

044610-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.833) question?

Stock #

R6478 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

128407066-128415619 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 128410194 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Lysine at position 256 (E256K)

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: E303K

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000032508
Gene: ENSMUSG00000030357
AA Change: E303K

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

probably damaging
Transcript: ENSMUST00000150387
AA Change: E256K

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000119930
Gene: ENSMUSG00000030357
AA Change: E256K

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 benign
Transcript: ENSMUST00000151796

SMART Domains

Protein: ENSMUSP00000122087
Gene: ENSMUSG00000030357

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

Meta Mutation Damage Score

0.4108

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 97.8%
20x: 93.3%

Validation Efficiency

95% (75/79)

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: 78 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aatk	T	A	11: 119,901,817 (GRCm39)	S803C	probably benign	Het
Abcc9	C	T	6: 142,625,034 (GRCm39)	A454T	probably damaging	Het
Abr	T	C	11: 76,343,158 (GRCm39)	E565G	probably damaging	Het
Adam33	C	A	2: 130,893,266 (GRCm39)	R753L	probably benign	Het
Adgre1	A	G	17: 57,708,955 (GRCm39)	T49A	possibly damaging	Het
Ankra2	A	T	13: 98,404,950 (GRCm39)	H153L	probably damaging	Het
Ankrd26	T	G	6: 118,488,599 (GRCm39)	E1353D	probably benign	Het
Ankrd52	T	G	10: 128,215,200 (GRCm39)		probably null	Het
Arhgef10l	T	A	4: 140,270,068 (GRCm39)	T619S	possibly damaging	Het
Armh4	A	G	14: 50,010,789 (GRCm39)	V306A	possibly damaging	Het
Asgr1	T	C	11: 69,947,720 (GRCm39)	V130A	possibly damaging	Het
Atg10	C	A	13: 91,085,466 (GRCm39)	C161F	probably damaging	Het
Atm	A	T	9: 53,401,554 (GRCm39)	N1438K	probably damaging	Het
BC107364	T	A	3: 96,343,322 (GRCm39)		probably null	Het
Bcar3	G	T	3: 122,220,225 (GRCm39)	A41S	probably benign	Het
Btbd6	A	G	12: 112,940,932 (GRCm39)		probably benign	Het
Cchcr1	A	G	17: 35,835,600 (GRCm39)	T318A	possibly damaging	Het
Celsr1	A	T	15: 85,809,719 (GRCm39)	I2221N	probably damaging	Het
Cept1	C	T	3: 106,440,761 (GRCm39)	W48*	probably null	Het
Cfap161	T	A	7: 83,442,484 (GRCm39)	I85L	probably benign	Het
Clasp1	A	T	1: 118,439,910 (GRCm39)	R640*	probably null	Het
Col5a1	T	A	2: 27,842,448 (GRCm39)	I441N	unknown	Het
Col9a1	C	A	1: 24,224,486 (GRCm39)	L223I	unknown	Het
Dnah2	T	C	11: 69,406,836 (GRCm39)	D223G	probably benign	Het
Dnah8	G	A	17: 30,967,542 (GRCm39)	D2585N	probably benign	Het
Dpy19l1	A	T	9: 24,361,992 (GRCm39)	M129K	possibly damaging	Het
Ecpas	A	T	4: 58,810,785 (GRCm39)	I1524N	probably damaging	Het
Fcgbpl1	C	G	7: 27,854,798 (GRCm39)	P1808R	probably damaging	Het
Fcrl1	C	A	3: 87,296,946 (GRCm39)	H318Q	probably benign	Het
Fer1l5	A	G	1: 36,441,612 (GRCm39)	N609S	probably damaging	Het
Fsip2	A	G	2: 82,820,430 (GRCm39)	T5388A	possibly damaging	Het
Glrx	G	A	13: 75,995,418 (GRCm39)		probably null	Het
Gm7356	A	T	17: 14,221,726 (GRCm39)	M101K	probably damaging	Het
Gstp2	A	T	19: 4,090,499 (GRCm39)	I162N	probably benign	Het
Hectd3	A	C	4: 116,856,783 (GRCm39)	K443N	probably damaging	Het
Hmcn1	T	A	1: 150,540,535 (GRCm39)	R2925W	probably damaging	Het
Hspa1a	G	T	17: 35,189,282 (GRCm39)	N540K	probably damaging	Het
Ints6	A	T	14: 62,938,235 (GRCm39)	M649K	probably benign	Het
Katnb1	T	C	8: 95,822,084 (GRCm39)	V270A	possibly damaging	Het
Kctd3	A	G	1: 188,704,561 (GRCm39)	S737P	probably benign	Het
Klra10	T	C	6: 130,249,507 (GRCm39)		probably null	Het
Lmtk3	A	G	7: 45,448,013 (GRCm39)	D1353G	unknown	Het
Lrrk1	A	G	7: 65,912,481 (GRCm39)	V1693A	probably damaging	Het
Mpnd	A	T	17: 56,316,575 (GRCm39)	I85F	probably damaging	Het
Myo3b	A	G	2: 70,179,304 (GRCm39)	T1173A	probably benign	Het
Myof	G	A	19: 37,892,279 (GRCm39)	P1158L	probably damaging	Het
Naip2	A	C	13: 100,298,549 (GRCm39)	S496A	probably benign	Het
Ncor2	A	G	5: 125,187,069 (GRCm39)		probably benign	Het
Npepps	C	T	11: 97,149,099 (GRCm39)		probably null	Het
Opn5	T	A	17: 42,891,640 (GRCm39)	I266F	probably benign	Het
Or4a74	T	G	2: 89,439,790 (GRCm39)	I219L	probably damaging	Het
P2rx4	A	G	5: 122,845,763 (GRCm39)	D16G	probably damaging	Het
Padi2	G	T	4: 140,644,948 (GRCm39)	V61L	probably benign	Het
Pkd1l1	G	A	11: 8,813,911 (GRCm39)	T1480I	probably benign	Het
Plcb1	T	C	2: 135,177,371 (GRCm39)	S568P	probably damaging	Het
Rassf10	A	G	7: 112,554,914 (GRCm39)	E505G	probably damaging	Het
Rcan2	A	G	17: 44,147,225 (GRCm39)	E21G	probably benign	Het
Rhob	G	T	12: 8,549,585 (GRCm39)	C16*	probably null	Het
Ryr3	T	C	2: 112,490,413 (GRCm39)	N3807S	probably damaging	Het
Sass6	T	A	3: 116,415,046 (GRCm39)	N519K	probably benign	Het
Slco1a8	A	T	6: 141,939,368 (GRCm39)	N208K	possibly damaging	Het
Smad9	A	T	3: 54,689,864 (GRCm39)	D28V	probably damaging	Het
Spmip8	A	T	8: 96,047,894 (GRCm39)		probably null	Het
Tex14	G	T	11: 87,405,199 (GRCm39)	G704C	probably benign	Het
Tmc3	A	G	7: 83,271,524 (GRCm39)	N892S	probably benign	Het
Tnfaip2	T	A	12: 111,412,097 (GRCm39)	L166Q	probably damaging	Het
Triml2	A	G	8: 43,638,165 (GRCm39)		probably null	Het
Trio	A	G	15: 27,856,193 (GRCm39)	V666A	probably benign	Het
Tshz2	G	T	2: 169,726,584 (GRCm39)	L393F	probably damaging	Het
Ttn	T	G	2: 76,672,115 (GRCm39)		probably benign	Het
Tubb5	A	G	17: 36,146,734 (GRCm39)	Y159H	probably damaging	Het
Umodl1	A	G	17: 31,178,129 (GRCm39)	Y35C	probably damaging	Het
Utp4	T	C	8: 107,631,078 (GRCm39)		probably null	Het
Vmn1r60	A	T	7: 5,547,864 (GRCm39)	C79S	probably damaging	Het
Wnt5b	T	C	6: 119,410,751 (GRCm39)	T230A	probably damaging	Het
Zfp618	A	T	4: 63,050,943 (GRCm39)	I575F	probably damaging	Het
Zmym6	G	T	4: 127,017,176 (GRCm39)	V894L	possibly damaging	Het
Zpbp	T	C	11: 11,412,318 (GRCm39)		probably benign	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
R0491:Fkbp4	UTSW	6	128,412,705 (GRCm39)	missense	probably damaging	1.00
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
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'- GGGTTCTCACCGATACATCC -3'
(R):5'- TACCCAGTGTGTCTTAGTCCG -3'

Sequencing Primer
(F):5'- GGTTCTCACCGATACATCCTACTAAC -3'
(R):5'- AGTCCGTTTGCTCTGGGAC -3'

Posted On

2018-05-21