Mutagenetix > Incidental Mutation

Incidental Mutation 'R4917:Gfra1'

378344

Institutional Source

Beutler Lab

Gene Symbol

Gfra1

Ensembl Gene

ENSMUSG00000025089

Gene Name

glial cell line derived neurotrophic factor family receptor alpha 1

Synonyms

GFR alpha-1, GDNFR-alpha

MMRRC Submission

042519-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4917 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

58224036-58444341 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 58255522 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Arginine at position 308 (S308R)

Ref Sequence

ENSEMBL: ENSMUSP00000130128 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000026076] [ENSMUST00000129100] [ENSMUST00000140141] [ENSMUST00000152507] [ENSMUST00000169850]

AlphaFold

P97785

Predicted Effect

probably damaging
Transcript: ENSMUST00000026076
AA Change: S308R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000026076
Gene: ENSMUSG00000025089
AA Change: S308R

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
GDNF	29	111	1.96e-13	SMART
GDNF	154	233	6.55e-24	SMART
GDNF	243	337	1.62e-28	SMART
low complexity region	362	370	N/A	INTRINSIC
low complexity region	455	465	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000129100
AA Change: S303R

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000117196
Gene: ENSMUSG00000025089
AA Change: S303R

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
GDNF	29	111	1.96e-13	SMART
GDNF	149	228	6.55e-24	SMART
GDNF	238	332	1.62e-28	SMART
low complexity region	357	365	N/A	INTRINSIC
low complexity region	450	460	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000140141
AA Change: S308R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000123022
Gene: ENSMUSG00000025089
AA Change: S308R

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
GDNF	29	111	1.96e-13	SMART
GDNF	154	233	6.55e-24	SMART
GDNF	243	337	1.62e-28	SMART
low complexity region	362	370	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000152507
AA Change: S308R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000120333
Gene: ENSMUSG00000025089
AA Change: S308R

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
GDNF	29	111	1.96e-13	SMART
GDNF	154	233	6.55e-24	SMART
GDNF	243	337	1.62e-28	SMART
low complexity region	362	370	N/A	INTRINSIC
low complexity region	455	465	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000169850
AA Change: S308R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000130128
Gene: ENSMUSG00000025089
AA Change: S308R

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
GDNF	29	111	1.96e-13	SMART
GDNF	154	233	6.55e-24	SMART
GDNF	243	337	1.62e-28	SMART
low complexity region	362	370	N/A	INTRINSIC
low complexity region	455	465	N/A	INTRINSIC

Meta Mutation Damage Score

0.5256

Coding Region Coverage

1x: 99.0%
3x: 98.3%
10x: 96.1%
20x: 91.7%

Validation Efficiency

97% (111/114)

MGI Phenotype

FUNCTION: This gene encodes a transmembrane protein that functions as the receptor for glial cell line derived neurotrophic factor (GDNF). The encoded protein undergoes proteolytic processing to generate a glycosylphosphatidylinositol-anchored cell surface coreceptor that forms a complex with the Ret tyrosine kinase in GDNF signaling pathway. Mice lacking the encoded protein exhibit deficits in the kidneys, the enteric nervous system, and spinal motor and sensory neurons similar mice deficient in GDNF or Ret. [provided by RefSeq, Jul 2016]
PHENOTYPE: Homozygotes for targeted null mutations lack kidneys and enteric neurons resulting in neonatal lethality. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 92 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adgrv1	C	T	13: 81,658,996 (GRCm39)	V2783I	probably benign	Het
Ago4	A	C	4: 126,400,635 (GRCm39)	C693G	probably damaging	Het
Apobec2	T	C	17: 48,730,153 (GRCm39)	E171G	probably benign	Het
Arfgef3	T	A	10: 18,492,638 (GRCm39)	I1258F	probably damaging	Het
Arhgef40	A	G	14: 52,227,556 (GRCm39)	E434G	probably damaging	Het
Bcas1	T	C	2: 170,220,806 (GRCm39)	D324G	probably damaging	Het
Bdp1	A	T	13: 100,191,713 (GRCm39)	V1422E	probably damaging	Het
Bfsp1	C	T	2: 143,669,391 (GRCm39)	R396Q	probably benign	Het
Bpifb9b	T	A	2: 154,156,026 (GRCm39)		probably null	Het
Cacna1s	T	A	1: 136,029,302 (GRCm39)		probably null	Het
Casp8	T	C	1: 58,866,377 (GRCm39)	F126S	probably damaging	Het
Cdh26	T	C	2: 178,091,614 (GRCm39)	S58P	probably benign	Het
Cds2	A	G	2: 132,140,398 (GRCm39)	T182A	probably damaging	Het
Cfap157	C	T	2: 32,669,965 (GRCm39)	R206H	probably benign	Het
Col7a1	G	A	9: 108,795,532 (GRCm39)	G1529E	unknown	Het
Crybg3	A	G	16: 59,350,782 (GRCm39)	F2567L	probably benign	Het
Cyp2e1	T	C	7: 140,354,527 (GRCm39)	S393P	possibly damaging	Het
D5Ertd579e	A	G	5: 36,773,160 (GRCm39)	Y412H	probably damaging	Het
Dclk2	A	T	3: 86,732,049 (GRCm39)		probably null	Het
Ddx50	A	T	10: 62,463,450 (GRCm39)	C414*	probably null	Het
Dip2c	T	A	13: 9,671,905 (GRCm39)		probably null	Het
Dmtn	G	T	14: 70,843,159 (GRCm39)	P283Q	probably damaging	Het
Dspp	C	A	5: 104,325,789 (GRCm39)	D717E	unknown	Het
Efcab11	T	C	12: 99,685,321 (GRCm39)	D151G	probably damaging	Het
Egfem1	T	C	3: 29,206,042 (GRCm39)	V93A	probably damaging	Het
Ehbp1	T	C	11: 22,096,592 (GRCm39)	D299G	probably benign	Het
Erlec1	A	G	11: 30,884,710 (GRCm39)	Y448H	possibly damaging	Het
Fer1l4	T	C	2: 155,873,220 (GRCm39)	K1287E	probably benign	Het
Fn1	A	T	1: 71,634,968 (GRCm39)		probably null	Het
Fut8	G	T	12: 77,521,818 (GRCm39)	A486S	probably damaging	Het
Gm10764	A	G	10: 87,126,579 (GRCm39)		noncoding transcript	Het
Gm5958	C	A	14: 100,073,189 (GRCm39)		noncoding transcript	Het
Gm6788	C	T	19: 28,740,664 (GRCm39)		noncoding transcript	Het
Gsdmd	A	G	15: 75,736,241 (GRCm39)	I123M	probably benign	Het
H2bc13	A	T	13: 21,900,189 (GRCm39)	V42E	probably damaging	Het
Hsf4	A	G	8: 105,999,367 (GRCm39)	E235G	probably benign	Het
Ighv1-83	T	C	12: 115,927,580 (GRCm39)	I57V	probably benign	Het
Inhca	A	C	9: 103,129,054 (GRCm39)	Y235*	probably null	Het
Inpp5f	A	T	7: 128,286,840 (GRCm39)	D573V	probably damaging	Het
Kcnj1	T	A	9: 32,308,056 (GRCm39)	L160Q	probably damaging	Het
Kcnmb3	A	T	3: 32,526,653 (GRCm39)	C179*	probably null	Het
Lrig1	A	G	6: 94,586,700 (GRCm39)	F659L	probably damaging	Het
Lrrc3	T	C	10: 77,737,253 (GRCm39)	D61G	probably benign	Het
Marchf4	T	G	1: 72,467,938 (GRCm39)	S365R	probably benign	Het
Mccc1	A	G	3: 36,051,703 (GRCm39)	L32S	probably benign	Het
Mei4	A	G	9: 81,772,216 (GRCm39)	T10A	probably benign	Het
Meis1	T	C	11: 18,959,222 (GRCm39)		probably benign	Het
Mllt1	T	C	17: 57,206,813 (GRCm39)	T344A	probably benign	Het
Mmp11	C	T	10: 75,761,419 (GRCm39)	A31T	probably damaging	Het
Mrps28	A	G	3: 8,947,614 (GRCm39)		probably benign	Het
Mthfsl	A	C	9: 88,597,550 (GRCm39)	L67V	probably damaging	Het
Ncaph2	A	G	15: 89,244,574 (GRCm39)	I11V	probably damaging	Het
Ncdn	G	A	4: 126,643,731 (GRCm39)	L364F	possibly damaging	Het
Nfat5	T	A	8: 108,051,284 (GRCm39)	D47E	probably damaging	Het
Or51g2	A	T	7: 102,622,614 (GRCm39)	I195N	possibly damaging	Het
Or5b106	T	A	19: 13,123,355 (GRCm39)	I223L	possibly damaging	Het
Or5bw2	C	T	7: 6,573,643 (GRCm39)	L218F	possibly damaging	Het
Pcdhb3	A	T	18: 37,435,452 (GRCm39)	I473F	probably damaging	Het
Pcdhgb8	A	T	18: 37,897,191 (GRCm39)	N754Y	probably damaging	Het
Pgbd5	C	A	8: 125,097,305 (GRCm39)	K408N	probably benign	Het
Pnisr	A	G	4: 21,859,330 (GRCm39)		probably benign	Het
Poldip3	A	T	15: 83,016,776 (GRCm39)		probably null	Het
Ppfia2	G	C	10: 106,597,978 (GRCm39)	L180F	probably damaging	Het
Psmc3	A	G	2: 90,896,317 (GRCm39)		probably benign	Het
Rab3gap1	T	A	1: 127,816,914 (GRCm39)	W58R	possibly damaging	Het
Rere	T	A	4: 150,703,601 (GRCm39)	W1528R	probably damaging	Het
Rhot1	A	G	11: 80,100,027 (GRCm39)		probably benign	Het
Rsf1	T	C	7: 97,311,612 (GRCm39)	S781P	probably damaging	Het
Rtraf	T	C	14: 19,873,784 (GRCm39)	K5R	probably damaging	Het
Rufy4	T	C	1: 74,186,822 (GRCm39)	C537R	probably damaging	Het
Ryr2	A	G	13: 11,609,872 (GRCm39)	V753A	probably damaging	Het
Ryr3	T	C	2: 112,661,530 (GRCm39)	H1820R	probably damaging	Het
Schip1	A	T	3: 68,315,818 (GRCm39)		probably benign	Het
Scin	T	A	12: 40,119,373 (GRCm39)	I552F	possibly damaging	Het
Selp	A	C	1: 163,972,475 (GRCm39)	T705P	probably damaging	Het
Sh3rf3	A	T	10: 58,842,925 (GRCm39)	D297V	probably damaging	Het
Slc24a4	T	A	12: 102,231,203 (GRCm39)		probably null	Het
Slc2a9	C	A	5: 38,574,603 (GRCm39)	L224F	probably benign	Het
Slc35e2	C	A	4: 155,700,693 (GRCm39)	P272Q	probably damaging	Het
Slf2	T	G	19: 44,960,100 (GRCm39)	D1022E	probably damaging	Het
Syne1	C	T	10: 5,007,909 (GRCm39)	C7932Y	probably damaging	Het
Tc2n	A	G	12: 101,631,954 (GRCm39)	L301P	probably damaging	Het
Tchhl1	A	G	3: 93,377,623 (GRCm39)	D109G	possibly damaging	Het
Thoc7	T	C	14: 13,953,154 (GRCm38)	I83V	probably damaging	Het
Tm4sf1	C	T	3: 57,200,448 (GRCm39)	G85S	probably damaging	Het
Tmem63a	T	A	1: 180,794,086 (GRCm39)	I541N	probably benign	Het
Tmpo	A	G	10: 90,985,411 (GRCm39)	V357A	probably damaging	Het
Unc80	T	C	1: 66,685,709 (GRCm39)	Y2278H	possibly damaging	Het
Vmn1r26	A	G	6: 57,985,808 (GRCm39)	F127S	probably damaging	Het
Vmn2r8	A	T	5: 108,945,264 (GRCm39)	M781K	probably damaging	Het
Vps36	T	G	8: 22,708,280 (GRCm39)	M348R	possibly damaging	Het
Vps45	T	C	3: 95,926,943 (GRCm39)	T535A	probably damaging	Het

Other mutations in Gfra1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00820:Gfra1	APN	19	58,252,337 (GRCm39)	splice site	probably benign
IGL01633:Gfra1	APN	19	58,255,479 (GRCm39)	missense	probably benign	0.41
IGL02675:Gfra1	APN	19	58,441,787 (GRCm39)	missense	probably damaging	1.00
IGL02676:Gfra1	APN	19	58,441,787 (GRCm39)	missense	probably damaging	1.00
IGL02677:Gfra1	APN	19	58,441,787 (GRCm39)	missense	probably damaging	1.00
IGL02723:Gfra1	APN	19	58,441,683 (GRCm39)	missense	probably benign	0.00
3-1:Gfra1	UTSW	19	58,286,999 (GRCm39)	intron	probably benign
R0245:Gfra1	UTSW	19	58,288,986 (GRCm39)	missense	possibly damaging	0.72
R0652:Gfra1	UTSW	19	58,288,986 (GRCm39)	missense	possibly damaging	0.72
R0697:Gfra1	UTSW	19	58,258,555 (GRCm39)	missense	probably benign
R0699:Gfra1	UTSW	19	58,258,555 (GRCm39)	missense	probably benign
R1344:Gfra1	UTSW	19	58,226,849 (GRCm39)	missense	possibly damaging	0.88
R1418:Gfra1	UTSW	19	58,226,849 (GRCm39)	missense	possibly damaging	0.88
R1468:Gfra1	UTSW	19	58,440,407 (GRCm39)	missense	probably benign	0.00
R1468:Gfra1	UTSW	19	58,440,407 (GRCm39)	missense	probably benign	0.00
R2001:Gfra1	UTSW	19	58,288,707 (GRCm39)	missense	probably damaging	1.00
R2866:Gfra1	UTSW	19	58,227,739 (GRCm39)	missense	possibly damaging	0.93
R3416:Gfra1	UTSW	19	58,255,544 (GRCm39)	missense	probably damaging	1.00
R4352:Gfra1	UTSW	19	58,255,456 (GRCm39)	missense	probably benign	0.08
R4564:Gfra1	UTSW	19	58,227,682 (GRCm39)	splice site	probably null
R4727:Gfra1	UTSW	19	58,252,386 (GRCm39)	missense	probably damaging	0.96
R4755:Gfra1	UTSW	19	58,441,676 (GRCm39)	missense	probably damaging	1.00
R4914:Gfra1	UTSW	19	58,255,522 (GRCm39)	missense	probably damaging	1.00
R4915:Gfra1	UTSW	19	58,255,522 (GRCm39)	missense	probably damaging	1.00
R5813:Gfra1	UTSW	19	58,227,687 (GRCm39)	missense	probably benign
R6225:Gfra1	UTSW	19	58,226,830 (GRCm39)	missense	probably damaging	1.00
R7023:Gfra1	UTSW	19	58,442,764 (GRCm39)	missense	probably damaging	1.00
R7485:Gfra1	UTSW	19	58,288,744 (GRCm39)	missense	probably damaging	1.00
R7624:Gfra1	UTSW	19	58,226,878 (GRCm39)	missense	probably benign
R7718:Gfra1	UTSW	19	58,441,889 (GRCm39)	missense	possibly damaging	0.69
R9659:Gfra1	UTSW	19	58,441,652 (GRCm39)	missense	probably damaging	1.00
R9788:Gfra1	UTSW	19	58,441,652 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CTGCTGTGTCACTGAGCATACC -3'
(R):5'- CCATGGCGTTTGTGACTAGC -3'

Sequencing Primer
(F):5'- GCTGTGTCACTGAGCATACCAAAAG -3'
(R):5'- AGCTGTGACATTTCTACTGTCAGAGC -3'

Posted On

2016-04-15