Mutagenetix > Incidental Mutation

Incidental Mutation 'R6225:Gfra1'

504307

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

044356-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6225 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

58224036-58444341 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 58226830 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Isoleucine at position 462 (T462I)

Ref Sequence

ENSEMBL: ENSMUSP00000117196 (fasta)

Gene Model

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

AlphaFold

P97785

Predicted Effect

probably damaging
Transcript: ENSMUST00000026076
AA Change: T467I

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000026076
Gene: ENSMUSG00000025089
AA Change: T467I

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: T462I

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

SMART Domains

Protein: ENSMUSP00000117196
Gene: ENSMUSG00000025089
AA Change: T462I

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 benign
Transcript: ENSMUST00000140141

SMART Domains

Protein: ENSMUSP00000123022
Gene: ENSMUSG00000025089

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

noncoding transcript
Transcript: ENSMUST00000143595

Predicted Effect

probably damaging
Transcript: ENSMUST00000152507
AA Change: T467I

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000120333
Gene: ENSMUSG00000025089
AA Change: T467I

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: T467I

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000130128
Gene: ENSMUSG00000025089
AA Change: T467I

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

Coding Region Coverage

1x: 99.9%
3x: 99.7%
10x: 98.3%
20x: 95.2%

Validation Efficiency

100% (74/74)

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: 76 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Ace	A	G	11: 105,870,445 (GRCm39)	H288R	possibly damaging	Het
Adh1	T	C	3: 137,995,565 (GRCm39)	F323L	probably benign	Het
Adss1	A	C	12: 112,600,837 (GRCm39)	H226P	probably damaging	Het
Ahrr	A	G	13: 74,371,031 (GRCm39)	S230P	possibly damaging	Het
Akap9	T	C	5: 4,012,105 (GRCm39)	V936A	probably damaging	Het
B4galnt2	A	G	11: 95,759,268 (GRCm39)	Y339H	probably damaging	Het
Bltp1	T	C	3: 37,002,453 (GRCm39)	V1466A	probably damaging	Het
C4b	C	A	17: 34,957,848 (GRCm39)	G611V	possibly damaging	Het
Cacna1i	A	G	15: 80,205,427 (GRCm39)	M128V	probably damaging	Het
Chia1	T	C	3: 106,038,213 (GRCm39)	S370P	possibly damaging	Het
Cops6	T	C	5: 138,159,673 (GRCm39)	V9A	possibly damaging	Het
D630003M21Rik	A	T	2: 158,059,321 (GRCm39)	I193K	probably benign	Het
Daam2	T	C	17: 49,801,467 (GRCm39)	D90G	probably damaging	Het
Fads3	A	G	19: 10,019,202 (GRCm39)	D36G	probably benign	Het
Fam185a	T	C	5: 21,630,554 (GRCm39)	V130A	probably damaging	Het
Fbn1	A	T	2: 125,172,463 (GRCm39)	N1928K	probably damaging	Het
Fstl3	A	G	10: 79,615,843 (GRCm39)	M110V	probably benign	Het
G2e3	A	G	12: 51,415,919 (GRCm39)	T552A	possibly damaging	Het
Glrx2	T	A	1: 143,621,121 (GRCm39)		probably benign	Het
Gm10100	G	T	10: 77,562,498 (GRCm39)	C60F	possibly damaging	Het
Gm43302	T	A	5: 105,425,605 (GRCm39)	K275*	probably null	Het
Gm6569	A	G	15: 73,711,640 (GRCm39)		probably benign	Het
Herc6	G	T	6: 57,639,139 (GRCm39)	V867L	possibly damaging	Het
Hhipl2	T	A	1: 183,209,459 (GRCm39)		probably null	Het
Kcnj16	A	T	11: 110,916,378 (GRCm39)	K347*	probably null	Het
Kcnt2	T	A	1: 140,354,661 (GRCm39)	C305*	probably null	Het
Large2	A	G	2: 92,196,825 (GRCm39)	L477P	probably damaging	Het
Lnpep	T	C	17: 17,799,245 (GRCm39)	T137A	possibly damaging	Het
Mettl3	T	C	14: 52,534,215 (GRCm39)		probably null	Het
Mical3	C	T	6: 120,935,684 (GRCm39)	S1614N	probably damaging	Het
Mmut	T	A	17: 41,249,622 (GRCm39)	V199E	possibly damaging	Het
Morc3	C	A	16: 93,642,082 (GRCm39)	Y100*	probably null	Het
Mrc2	A	G	11: 105,237,646 (GRCm39)	K1108R	probably benign	Het
Mrpl2	T	C	17: 46,960,835 (GRCm39)	V243A	probably damaging	Het
Mtor	T	A	4: 148,605,794 (GRCm39)	N1505K	probably benign	Het
Myo1g	A	T	11: 6,469,168 (GRCm39)	Y45N	probably damaging	Het
Nckap5l	C	A	15: 99,325,905 (GRCm39)	L199F	possibly damaging	Het
Ndufc2	A	G	7: 97,056,099 (GRCm39)	T66A	probably damaging	Het
Nos1	T	A	5: 118,050,917 (GRCm39)	H779Q	probably damaging	Het
Or12e13	A	G	2: 87,663,661 (GRCm39)	T93A	probably benign	Het
Or13j1	T	C	4: 43,705,698 (GRCm39)	Y290C	probably damaging	Het
Or1e23	T	C	11: 73,407,831 (GRCm39)	N65D	probably damaging	Het
Or4c3	A	G	2: 89,851,573 (GRCm39)		probably null	Het
Or51ah3	A	T	7: 103,210,489 (GRCm39)	R268S	probably benign	Het
Or5au1	C	A	14: 52,272,825 (GRCm39)	V248L	possibly damaging	Het
Or5k16	T	C	16: 58,736,545 (GRCm39)	N153S	probably benign	Het
Otog	C	T	7: 45,898,458 (GRCm39)	T192I	possibly damaging	Het
Oxct1	T	C	15: 4,064,812 (GRCm39)	V50A	probably benign	Het
P3h2	T	A	16: 25,784,493 (GRCm39)	D667V	probably damaging	Het
Pcdhb20	A	G	18: 37,638,047 (GRCm39)	Y191C	probably damaging	Het
Pds5b	T	G	5: 150,670,083 (GRCm39)	V357G	probably damaging	Het
Pggt1b	A	G	18: 46,407,674 (GRCm39)	V81A	possibly damaging	Het
Phxr2	A	G	10: 98,962,043 (GRCm39)		probably benign	Het
Pnpt1	T	C	11: 29,095,469 (GRCm39)	I406T	probably benign	Het
Ppat	T	C	5: 77,070,202 (GRCm39)	I173V	probably damaging	Het
Proser3	T	C	7: 30,243,153 (GRCm39)	S167G	probably damaging	Het
Rnf135	A	C	11: 80,080,053 (GRCm39)	T115P	possibly damaging	Het
Rpl22	C	T	4: 152,414,536 (GRCm39)	R65C	probably benign	Het
Scel	T	C	14: 103,829,420 (GRCm39)	F405L	probably benign	Het
Serinc3	A	G	2: 163,469,799 (GRCm39)	Y350H	probably damaging	Het
Slc25a16	C	A	10: 62,764,102 (GRCm39)	T53K	probably damaging	Het
Slco1a1	A	T	6: 141,870,215 (GRCm39)	F308I	possibly damaging	Het
Slitrk5	GACTAC	GACTACTAC	14: 111,917,248 (GRCm39)		probably benign	Het
Smok3c	T	C	5: 138,063,314 (GRCm39)	V267A	probably benign	Het
Ssrp1	A	G	2: 84,873,158 (GRCm39)	D473G	probably benign	Het
Svs6	A	G	2: 164,159,405 (GRCm39)	E56G	possibly damaging	Het
Tas2r130	TCATTTC	T	6: 131,607,547 (GRCm39)		probably benign	Het
Thoc3	T	C	13: 54,615,785 (GRCm39)	N93S	probably benign	Het
Tle6	A	G	10: 81,428,600 (GRCm39)	C443R	probably damaging	Het
Tmed6	A	G	8: 107,788,371 (GRCm39)	F192S	probably damaging	Het
Tpx2	A	G	2: 152,718,548 (GRCm39)	N184D	probably benign	Het
Vmn2r31	T	A	7: 7,397,638 (GRCm39)	N207Y	probably benign	Het
Zfp267	T	C	3: 36,220,352 (GRCm39)	F792L	probably benign	Het
Zfp709	TCGACG	TCG	8: 72,644,552 (GRCm39)		probably benign	Het
Zfp972	A	T	2: 177,549,117 (GRCm39)		probably null	Het
Zzef1	G	A	11: 72,760,631 (GRCm39)	C1318Y	possibly 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
R4917:Gfra1	UTSW	19	58,255,522 (GRCm39)	missense	probably damaging	1.00
R5813:Gfra1	UTSW	19	58,227,687 (GRCm39)	missense	probably benign
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'- CAGTTCTTCAACAGAAGCCTG -3'
(R):5'- ACGGGTAAAATCCAACCTGAGG -3'

Sequencing Primer
(F):5'- CCTGTGAGGGCGGCAAAAAG -3'
(R):5'- TCCAACCTGAGGAAGTGGGC -3'

Posted On

2018-02-28