Mutagenetix > Incidental Mutation

Incidental Mutation 'R5196:Fgd4'

400281

Institutional Source

Beutler Lab

Gene Symbol

Fgd4

Ensembl Gene

ENSMUSG00000022788

Gene Name

FYVE, RhoGEF and PH domain containing 4

Synonyms

Frabin-alpha, 9330209B17Rik, ZFYVE6, Frabin-gamma, Frabin-beta, Frabin

MMRRC Submission

042772-MU

Accession Numbers

Genbank: NM_139232; MGI: 2183747

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R5196 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

16416917-16600549 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 16484142 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Isoleucine at position 183 (N183I)

Ref Sequence

ENSEMBL: ENSMUSP00000125736 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000069284] [ENSMUST00000159542] [ENSMUST00000161188] [ENSMUST00000161861] [ENSMUST00000162671]

AlphaFold

Q91ZT5

Predicted Effect

probably benign
Transcript: ENSMUST00000069284
AA Change: N183I

PolyPhen 2 Score 0.004 (Sensitivity: 0.98; Specificity: 0.59)

SMART Domains

Protein: ENSMUSP00000069573
Gene: ENSMUSG00000022788
AA Change: N183I

Domain	Start	End	E-Value	Type
RhoGEF	210	392	1.48e-57	SMART
PH	423	523	1.91e-19	SMART
FYVE	551	620	2.2e-30	SMART
PH	644	742	1.31e-8	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000159058

Predicted Effect

probably benign
Transcript: ENSMUST00000159542
AA Change: N183I

PolyPhen 2 Score 0.006 (Sensitivity: 0.97; Specificity: 0.75)

SMART Domains

Protein: ENSMUSP00000125649
Gene: ENSMUSG00000022788
AA Change: N183I

Domain	Start	End	E-Value	Type
RhoGEF	210	392	1.48e-57	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000161188
AA Change: N183I

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)

SMART Domains

Protein: ENSMUSP00000123763
Gene: ENSMUSG00000022788
AA Change: N183I

Domain	Start	End	E-Value	Type
RhoGEF	210	392	1.48e-57	SMART
PH	423	523	1.91e-19	SMART
FYVE	551	603	1.94e-8	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000161624

Predicted Effect

probably benign
Transcript: ENSMUST00000161861
AA Change: N183I

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)

SMART Domains

Protein: ENSMUSP00000125174
Gene: ENSMUSG00000022788
AA Change: N183I

Domain	Start	End	E-Value	Type
RhoGEF	210	392	1.48e-57	SMART
PH	423	523	1.91e-19	SMART
FYVE	551	620	2.2e-30	SMART
PH	644	742	1.31e-8	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000162045

SMART Domains

Protein: ENSMUSP00000125435
Gene: ENSMUSG00000022788

Domain	Start	End	E-Value	Type
RhoGEF	210	392	1.48e-57	SMART
PH	423	504	2.36e-1	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000162124

SMART Domains

Protein: ENSMUSP00000125165
Gene: ENSMUSG00000022788

Domain	Start	End	E-Value	Type
RhoGEF	166	348	1.48e-57	SMART
PH	379	460	2.36e-1	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000162414

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000162542

Predicted Effect

probably benign
Transcript: ENSMUST00000162671
AA Change: N183I

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)

SMART Domains

Protein: ENSMUSP00000125736
Gene: ENSMUSG00000022788
AA Change: N183I

Domain	Start	End	E-Value	Type
RhoGEF	210	392	1.48e-57	SMART
PH	423	523	1.91e-19	SMART
FYVE	551	620	2.2e-30	SMART
PH	644	742	1.31e-8	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000172181

SMART Domains

Protein: ENSMUSP00000131870
Gene: ENSMUSG00000022788

Domain	Start	End	E-Value	Type
RhoGEF	210	392	1.48e-57	SMART
PH	423	523	1.91e-19	SMART
FYVE	551	603	1.94e-8	SMART

Meta Mutation Damage Score

0.1866

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.9%
20x: 94.3%

Validation Efficiency

100% (62/62)

MGI Phenotype

FUNCTION: This gene is a member of the FYVE, RhoGEF and PH domain containing (FGD) family. The encoded protein is a Cdc42-specific guanine nucleotide exchange factor (GEF) that plays an essential role in regulating the actin cytoskeleton and cell morphology. Disruption of the gene in mouse causes abnormal nerve development and dysmyelination. Mutations in a similar gene in human can cause Charcot-Marie-Tooth disease type 4H (CMT4H), a disorder of the peripheral nervous system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]
PHENOTYPE: Mice homozygous for a knock-out allele display dysmyelination in early peripheral nerve development, followed by severe myelin abnormalities, demyelinationn, nervous system electrophysiological deficits, and decreased grip strength at later stages. [provided by MGI curators]

Allele List at MGI

All alleles(60) : Gene trapped(60)

Other mutations in this stock

Total: 52 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700001O22Rik	T	C	2: 30,796,438	T281A	possibly damaging	Het
4930503B20Rik	A	G	3: 146,646,263		probably benign	Het
6330409D20Rik	T	A	2: 32,740,540		probably benign	Het
Afg3l2	G	T	18: 67,421,259	L458M	probably damaging	Het
Amigo2	A	G	15: 97,246,061	F160S	probably damaging	Het
Arcn1	A	T	9: 44,760,027	L68M	probably damaging	Het
Arhgef25	A	G	10: 127,185,109	S303P	probably damaging	Het
Asph	A	T	4: 9,607,830	S163T	probably damaging	Het
BC003331	T	A	1: 150,382,389	D165V	probably damaging	Het
Birc6	T	C	17: 74,606,141		probably benign	Het
Ccm2	G	A	11: 6,561,181		probably benign	Het
Cdc42bpa	T	C	1: 180,072,413	V431A	probably benign	Het
Cdh7	T	A	1: 110,138,000	M668K	probably damaging	Het
Cfap43	A	T	19: 47,825,925	W157R	probably damaging	Het
Chrm5	T	C	2: 112,480,384	Y129C	probably damaging	Het
Chrna5	A	G	9: 55,006,519	I421V	possibly damaging	Het
Clk1	T	A	1: 58,414,613	T301S	probably benign	Het
Col6a3	G	T	1: 90,816,538		probably null	Het
Eml2	G	A	7: 19,201,163	V432I	probably damaging	Het
Fam198a	T	G	9: 121,965,661	S294A	probably benign	Het
Fbxw19	T	C	9: 109,484,428	Y234C	probably benign	Het
Fnip2	T	C	3: 79,572,538		probably benign	Het
Gm9847	T	A	12: 14,495,015		noncoding transcript	Het
H2-T23	A	G	17: 36,032,607		probably null	Het
Hdlbp	T	C	1: 93,420,193	E613G	probably damaging	Het
Kat6a	G	A	8: 22,911,713	R366H	probably damaging	Het
Kctd4	A	G	14: 75,962,687	T33A	probably benign	Het
Klrb1c	T	A	6: 128,780,299	S268C	probably benign	Het
Lgr6	C	T	1: 134,994,010	A199T	probably damaging	Het
Lrrfip1	A	G	1: 91,114,608	E245G	probably damaging	Het
Mast3	A	T	8: 70,788,245	I220N	probably damaging	Het
Mfap3	A	G	11: 57,529,813	T207A	probably damaging	Het
Mtdh	G	T	15: 34,118,004	K75N	probably damaging	Het
Mybpc1	A	G	10: 88,536,351	Y806H	probably damaging	Het
Ntng1	T	C	3: 109,934,983	D158G	probably damaging	Het
Olfr1176	A	G	2: 88,339,748	Y61C	possibly damaging	Het
Olfr812	T	A	10: 129,842,781	D87V	possibly damaging	Het
Pask	A	G	1: 93,310,083		probably benign	Het
Pif1	G	T	9: 65,588,092	A95S	probably benign	Het
Plppr2	T	C	9: 21,941,132	F104S	probably damaging	Het
Prmt9	G	A	8: 77,564,997	V333M	probably benign	Het
Pten	A	T	19: 32,815,497	M239L	probably benign	Het
Rb1cc1	A	G	1: 6,234,230	D67G	probably damaging	Het
Reg2	T	A	6: 78,405,547	L12*	probably null	Het
Rufy4	T	C	1: 74,147,663	C537R	probably damaging	Het
Slc5a7	C	A	17: 54,281,722		probably null	Het
Tcaf3	G	T	6: 42,593,715	R368S	probably benign	Het
Tfcp2	A	G	15: 100,520,714	V189A	probably damaging	Het
Uhrf1bp1	A	G	17: 27,856,763	I5V	probably benign	Het
Wdr12	T	C	1: 60,087,084	S191G	probably damaging	Het
Zfp536	G	A	7: 37,480,760	R807W	probably damaging	Het
Zfp647	G	A	15: 76,912,085	P125L	probably damaging	Het

Other mutations in Fgd4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01289:Fgd4	APN	16	16484303	missense	probably damaging	0.99
IGL01455:Fgd4	APN	16	16490490	missense	probably benign	0.22
IGL02035:Fgd4	APN	16	16490416	splice site	probably benign
IGL02353:Fgd4	APN	16	16462045	missense	probably damaging	0.96
IGL02360:Fgd4	APN	16	16462045	missense	probably damaging	0.96
IGL03100:Fgd4	APN	16	16477519	splice site	probably benign
11287:Fgd4	UTSW	16	16423923	missense	probably damaging	1.00
R0787:Fgd4	UTSW	16	16423901	splice site	probably benign
R0853:Fgd4	UTSW	16	16474387	splice site	probably benign
R0879:Fgd4	UTSW	16	16477449	missense	probably damaging	1.00
R1482:Fgd4	UTSW	16	16484473	missense	probably benign	0.39
R1619:Fgd4	UTSW	16	16424056	missense	possibly damaging	0.52
R1635:Fgd4	UTSW	16	16475029	nonsense	probably null
R2018:Fgd4	UTSW	16	16435960	missense	probably benign	0.15
R2120:Fgd4	UTSW	16	16425828	missense	probably benign	0.44
R2292:Fgd4	UTSW	16	16436000	missense	possibly damaging	0.95
R2902:Fgd4	UTSW	16	16425865	missense	probably damaging	1.00
R4575:Fgd4	UTSW	16	16437032	missense	probably damaging	1.00
R4747:Fgd4	UTSW	16	16423929	missense	probably damaging	1.00
R4941:Fgd4	UTSW	16	16484538	missense	probably benign
R5372:Fgd4	UTSW	16	16484291	missense	probably benign	0.03
R5457:Fgd4	UTSW	16	16462009	missense	probably benign	0.39
R5486:Fgd4	UTSW	16	16475037	missense	probably damaging	1.00
R6709:Fgd4	UTSW	16	16484481	missense	probably benign	0.09
R6962:Fgd4	UTSW	16	16484087	splice site	probably null
R7207:Fgd4	UTSW	16	16484556	missense	probably benign	0.11
R7732:Fgd4	UTSW	16	16484595	missense	probably benign
R7749:Fgd4	UTSW	16	16475154	missense	probably benign	0.02
R7846:Fgd4	UTSW	16	16422726	missense	probably damaging	1.00
R7937:Fgd4	UTSW	16	16469773	missense	probably damaging	1.00
R8517:Fgd4	UTSW	16	16422645	missense	probably benign	0.04
R8755:Fgd4	UTSW	16	16484269	missense	probably benign	0.00
R9015:Fgd4	UTSW	16	16454077	missense	probably damaging	1.00
R9055:Fgd4	UTSW	16	16422630	missense	possibly damaging	0.54
R9259:Fgd4	UTSW	16	16477461	missense	probably damaging	1.00
R9364:Fgd4	UTSW	16	16490489	missense	probably benign	0.08
R9554:Fgd4	UTSW	16	16490489	missense	probably benign	0.08
R9653:Fgd4	UTSW	16	16436597	missense	probably benign
R9682:Fgd4	UTSW	16	16484338	missense	probably benign
Z1088:Fgd4	UTSW	16	16484470	nonsense	probably null

Predicted Primers

PCR Primer
(F):5'- ATTAGCCTCCAAGCTTGCAAATG -3'
(R):5'- ACTACTCTTAGCCCAGAGATGG -3'

Sequencing Primer
(F):5'- CAAGCTTGCAAATGGTTTCTCTG -3'
(R):5'- CTCCTGATACACATGTGCTGAATGG -3'

Posted On

2016-07-06