Mutagenetix > Incidental Mutations

Incidental Mutation 'R0652:Gfra1'

62350

Institutional Source

Beutler Lab

Gene Symbol

Gfra1

Ensembl Gene

ENSMUSG00000025089

Gene Name

glial cell line derived neurotrophic factor family receptor alpha 1

Synonyms

GDNFR-alpha, GFR alpha-1

MMRRC Submission

038837-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R0652 (G1)

Quality Score

161

Status

Not validated

Chromosome

Chromosomal Location

58235604-58455909 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 58300554 bp

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Serine at position 153 (N153S)

Ref Sequence

ENSEMBL: ENSMUSP00000130128 (fasta)

Gene Model

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000026076
AA Change: N153S

PolyPhen 2 Score 0.724 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000026076
Gene: ENSMUSG00000025089
AA Change: N153S

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 benign
Transcript: ENSMUST00000129100
AA Change: N148S

PolyPhen 2 Score 0.021 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000117196
Gene: ENSMUSG00000025089
AA Change: N148S

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

possibly damaging
Transcript: ENSMUST00000140141
AA Change: N153S

PolyPhen 2 Score 0.481 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000123022
Gene: ENSMUSG00000025089
AA Change: N153S

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

possibly damaging
Transcript: ENSMUST00000152507
AA Change: N153S

PolyPhen 2 Score 0.724 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000120333
Gene: ENSMUSG00000025089
AA Change: N153S

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

possibly damaging
Transcript: ENSMUST00000169850
AA Change: N153S

PolyPhen 2 Score 0.724 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000130128
Gene: ENSMUSG00000025089
AA Change: N153S

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

0.0608

Coding Region Coverage

1x: 99.3%
3x: 98.5%
10x: 96.3%
20x: 90.1%

Validation Efficiency

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: 86 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca9	T	C	11: 110,152,063	N387D	probably benign	Het
Adgrg5	T	A	8: 94,934,157		probably null	Het
Ahi1	C	A	10: 20,979,461	H556Q	probably damaging	Het
Amph	A	G	13: 19,086,621		probably null	Het
Apol7a	T	C	15: 77,389,855		probably benign	Het
Apoo-ps	A	T	13: 107,414,410		noncoding transcript	Het
Arpc1b	A	G	5: 145,126,860	D306G	probably damaging	Het
Astn2	T	C	4: 65,794,558	D615G	probably damaging	Het
Atm	A	G	9: 53,486,014	V1673A	probably damaging	Het
B3gnt3	A	T	8: 71,693,822	V21E	probably benign	Het
Bco1	A	G	8: 117,105,696	D77G	probably damaging	Het
Brinp2	A	T	1: 158,246,621	H643Q	probably damaging	Het
Bsn	A	G	9: 108,105,742	F3604S	unknown	Het
Cacna1c	A	G	6: 118,602,229	F1753L	probably damaging	Het
Cd74	T	C	18: 60,811,885	S201P	probably damaging	Het
Cep192	T	A	18: 67,807,265	L101Q	probably benign	Het
Cfap161	T	C	7: 83,793,276	I110V	probably null	Het
Cnksr3	T	C	10: 7,120,463	D257G	probably damaging	Het
Col14a1	A	C	15: 55,344,882	E121A	unknown	Het
Cpne3	T	C	4: 19,532,486	D309G	probably benign	Het
Ctnnd1	A	G	2: 84,602,896	I609T	probably benign	Het
Cyp2s1	A	G	7: 25,809,258	V253A	probably damaging	Het
Dock7	T	C	4: 99,055,349	D552G	possibly damaging	Het
Dpyd	A	G	3: 119,427,275	D965G	probably damaging	Het
Efcab2	T	A	1: 178,481,346	M138K	probably damaging	Het
Eml3	T	C	19: 8,933,285	S204P	probably damaging	Het
Fbxw16	T	A	9: 109,436,168	S432C	possibly damaging	Het
Fbxw20	T	G	9: 109,232,332	Q116H	probably damaging	Het
Fech	A	G	18: 64,458,169	S395P	probably damaging	Het
Fgf7	A	G	2: 126,035,955	K81E	probably benign	Het
Fras1	T	A	5: 96,781,340	Y3868N	possibly damaging	Het
Ganab	A	T	19: 8,915,402		probably null	Het
Gja4	T	A	4: 127,312,127	Y281F	probably benign	Het
Gm15448	T	A	7: 3,822,763	Y369F	probably benign	Het
Gm4763	T	A	7: 24,724,197	N14I	possibly damaging	Het
Gm5141	T	C	13: 62,774,132	T407A	probably damaging	Het
Gm5422	T	C	10: 31,249,281		noncoding transcript	Het
Greb1	T	C	12: 16,696,456	Y1271C	probably damaging	Het
Hp1bp3	C	A	4: 138,228,769	N50K	possibly damaging	Het
Hspg2	T	C	4: 137,514,722	F589S	probably damaging	Het
Ido1	A	G	8: 24,585,244	F183S	probably damaging	Het
Iqgap1	T	A	7: 80,736,395	K936I	probably damaging	Het
Kdm4a	T	C	4: 118,175,689	D60G	probably benign	Het
L3mbtl4	G	A	17: 68,774,291	C558Y	probably damaging	Het
Lrrc28	T	C	7: 67,618,085	N98S	probably damaging	Het
Map1a	A	G	2: 121,302,783	D1360G	probably benign	Het
Megf10	C	T	18: 57,277,724	P702S	probably benign	Het
Met	A	G	6: 17,491,710	E157G	probably benign	Het
Mff	A	G	1: 82,750,564	D187G	possibly damaging	Het
Mlph	A	T	1: 90,942,908	I514F	possibly damaging	Het
Mroh2a	C	T	1: 88,230,680	R150*	probably null	Het
Myo15b	T	C	11: 115,864,642	V976A	probably benign	Het
Myo9a	A	G	9: 59,871,926	D1655G	probably benign	Het
Ncoa6	C	T	2: 155,391,211	G2059D	probably benign	Het
Ndst4	A	T	3: 125,611,539	H481L	possibly damaging	Het
Nipbl	A	G	15: 8,303,480	S2220P	probably benign	Het
Nom1	C	A	5: 29,435,311	P212T	probably damaging	Het
Nsd1	A	G	13: 55,247,586	D1000G	possibly damaging	Het
Nudt9	T	C	5: 104,050,601	F44S	possibly damaging	Het
Numb	C	T	12: 83,795,792	V537I	probably damaging	Het
Olfr1404	T	A	1: 173,215,957	I102N	possibly damaging	Het
Olfr1463	A	T	19: 13,234,535	Y95F	possibly damaging	Het
Olfr183	A	G	16: 58,999,700	N5S	probably damaging	Het
Olfr60	A	T	7: 140,345,632	M119K	probably damaging	Het
Olfr638	A	G	7: 104,003,239		probably null	Het
Olfr801	T	A	10: 129,670,379	T47S	probably benign	Het
Osgin1	A	T	8: 119,445,472	Y335F	probably damaging	Het
Pcdh10	T	A	3: 45,379,764	V171E	probably damaging	Het
Plxna4	T	C	6: 32,185,501	N1359S	probably damaging	Het
Ppp1r16a	C	T	15: 76,690,799		probably benign	Het
Prr5l	T	C	2: 101,772,290	T2A	possibly damaging	Het
Rbp3	T	A	14: 33,958,648	I1069N	possibly damaging	Het
Rnf144b	A	G	13: 47,220,507	Y60C	probably damaging	Het
Sbno2	A	T	10: 80,067,294	V396E	probably damaging	Het
Sdk1	A	G	5: 141,954,958	T494A	probably benign	Het
Serac1	G	T	17: 6,051,756	D384E	probably damaging	Het
Sgk1	A	G	10: 21,882,657	N7D	probably damaging	Het
Sigirr	A	T	7: 141,093,067	V69D	possibly damaging	Het
Slc17a3	C	T	13: 23,855,858	S293F	probably damaging	Het
St6gal2	T	C	17: 55,498,289	Y396H	probably benign	Het
Ttn	A	T	2: 76,768,612	F19319Y	probably damaging	Het
Ubr4	T	A	4: 139,401,326	I599N	probably damaging	Het
Vmn1r213	A	G	13: 23,011,394		probably benign	Het
Vmn2r96	T	A	17: 18,597,568	M469K	probably benign	Het
Wasf1	T	A	10: 40,931,906		probably null	Het
Wdr20rt	T	C	12: 65,225,915	S51P	probably damaging	Het

Other mutations in Gfra1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00820:Gfra1	APN	19	58263905	splice site	probably benign
IGL01633:Gfra1	APN	19	58267047	missense	probably benign	0.41
IGL02675:Gfra1	APN	19	58453355	missense	probably damaging	1.00
IGL02676:Gfra1	APN	19	58453355	missense	probably damaging	1.00
IGL02677:Gfra1	APN	19	58453355	missense	probably damaging	1.00
IGL02723:Gfra1	APN	19	58453251	missense	probably benign	0.00
3-1:Gfra1	UTSW	19	58298567	intron	probably benign
R0245:Gfra1	UTSW	19	58300554	missense	possibly damaging	0.72
R0697:Gfra1	UTSW	19	58270123	missense	probably benign
R0699:Gfra1	UTSW	19	58270123	missense	probably benign
R1344:Gfra1	UTSW	19	58238417	missense	possibly damaging	0.88
R1418:Gfra1	UTSW	19	58238417	missense	possibly damaging	0.88
R1468:Gfra1	UTSW	19	58451975	missense	probably benign	0.00
R1468:Gfra1	UTSW	19	58451975	missense	probably benign	0.00
R2001:Gfra1	UTSW	19	58300275	missense	probably damaging	1.00
R2866:Gfra1	UTSW	19	58239307	missense	possibly damaging	0.93
R3416:Gfra1	UTSW	19	58267112	missense	probably damaging	1.00
R4352:Gfra1	UTSW	19	58267024	missense	probably benign	0.08
R4564:Gfra1	UTSW	19	58239250	splice site	probably null
R4727:Gfra1	UTSW	19	58263954	missense	probably damaging	0.96
R4755:Gfra1	UTSW	19	58453244	missense	probably damaging	1.00
R4914:Gfra1	UTSW	19	58267090	missense	probably damaging	1.00
R4915:Gfra1	UTSW	19	58267090	missense	probably damaging	1.00
R4917:Gfra1	UTSW	19	58267090	missense	probably damaging	1.00
R5813:Gfra1	UTSW	19	58239255	missense	probably benign
R6225:Gfra1	UTSW	19	58238398	missense	probably damaging	1.00
R7023:Gfra1	UTSW	19	58454332	missense	probably damaging	1.00
R7485:Gfra1	UTSW	19	58300312	missense	probably damaging	1.00
R7624:Gfra1	UTSW	19	58238446	missense	probably benign
R7718:Gfra1	UTSW	19	58453457	missense	possibly damaging	0.69

Predicted Primers

PCR Primer
(F):5'- TCTTCATAGGAGCACACAGGGACG -3'
(R):5'- AGCTGAAAACAGTTCTCCAGTTGCC -3'

Sequencing Primer
(F):5'- AGGGACGATAGTCTGTCGC -3'
(R):5'- ACATCTAGGGACTACTGTAGGCTC -3'

Posted On

2013-07-30