Mutagenetix > Incidental Mutation

Incidental Mutation 'R1775:Ntrk3'

204326

Institutional Source

Beutler Lab

Gene Symbol

Ntrk3

Ensembl Gene

ENSMUSG00000059146

Gene Name

neurotrophic tyrosine kinase, receptor, type 3

Synonyms

TrkC

MMRRC Submission

039806-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1775 (G1)

Quality Score

170

Status

Validated

Chromosome

Chromosomal Location

78175959-78738012 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 78356041 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Leucine at position 524 (H524L)

Ref Sequence

ENSEMBL: ENSMUSP00000141599 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000039431] [ENSMUST00000039438] [ENSMUST00000193002] [ENSMUST00000195262]

AlphaFold

Q6VNS1

Predicted Effect

probably benign
Transcript: ENSMUST00000039431
AA Change: H524L

PolyPhen 2 Score 0.366 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000037909
Gene: ENSMUSG00000059146
AA Change: H524L

Domain	Start	End	E-Value	Type
LRRNT	31	63	2.46e-4	SMART
LRRCT	160	208	3.58e-12	SMART
IG	216	302	1.24e-8	SMART
Pfam:I-set	308	392	2.4e-8	PFAM
transmembrane domain	430	452	N/A	INTRINSIC
TyrKc	538	810	1.49e-145	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000039438
AA Change: H524L

PolyPhen 2 Score 0.366 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000038324
Gene: ENSMUSG00000059146
AA Change: H524L

Domain	Start	End	E-Value	Type
LRRNT	31	63	2.46e-4	SMART
LRRCT	160	208	3.58e-12	SMART
IG	216	302	1.24e-8	SMART
Pfam:I-set	308	392	3.1e-8	PFAM
transmembrane domain	429	451	N/A	INTRINSIC
PDB:2MFQ\|B	497	517	2e-6	PDB

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000151885

Predicted Effect

possibly damaging
Transcript: ENSMUST00000193002
AA Change: H524L

PolyPhen 2 Score 0.558 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000141534
Gene: ENSMUSG00000059146
AA Change: H524L

Domain	Start	End	E-Value	Type
LRRNT	31	63	2.46e-4	SMART
LRRCT	160	208	3.58e-12	SMART
IG	216	302	1.24e-8	SMART
Pfam:I-set	308	392	2.4e-8	PFAM
Pfam:Ig_2	312	392	6.9e-4	PFAM
transmembrane domain	430	452	N/A	INTRINSIC
TyrKc	538	824	4.29e-137	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000195262
AA Change: H524L

PolyPhen 2 Score 0.596 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000141599
Gene: ENSMUSG00000059146
AA Change: H524L

Domain	Start	End	E-Value	Type
LRRNT	31	63	1.2e-6	SMART
LRRCT	160	208	1.8e-14	SMART
IG	216	302	5.1e-11	SMART
Pfam:I-set	308	392	4.7e-7	PFAM
Pfam:Ig_2	312	392	1.3e-2	PFAM
transmembrane domain	430	452	N/A	INTRINSIC
TyrKc	538	849	9.7e-132	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000205312

Predicted Effect

probably benign
Transcript: ENSMUST00000206599

Meta Mutation Damage Score

0.0819

Coding Region Coverage

1x: 97.5%
3x: 97.0%
10x: 95.5%
20x: 92.9%

Validation Efficiency

98% (95/97)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the neurotrophic tyrosine receptor kinase (NTRK) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation and may play a role in the development of proprioceptive neurons that sense body position. Mutations in this gene have been associated with medulloblastomas, secretory breast carcinomas and other cancers. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]
PHENOTYPE: Homozygotes for targeted mutations show a range of phenotypes including postnatal death at 2-21 days, cardiac defects, reduced numbers of dorsal root ganglia neurons and germ cells, abnormal motor coordination and posture and abnormal sensory innervation. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 93 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700034J04Rik	A	G	12: 11,222,142 (GRCm38)	S20P	unknown	Het
4921528I07Rik	G	A	9: 114,279,318 (GRCm38)		noncoding transcript	Het
4930562C15Rik	G	A	16: 4,851,558 (GRCm38)		probably null	Het
4933427I04Rik	A	G	4: 123,860,493 (GRCm38)	T67A	possibly damaging	Het
Abcc2	A	T	19: 43,798,419 (GRCm38)	N160Y	possibly damaging	Het
Acaca	A	G	11: 84,300,422 (GRCm38)	D155G	possibly damaging	Het
Afg3l1	G	A	8: 123,492,900 (GRCm38)	R389Q	possibly damaging	Het
Ank2	G	A	3: 126,934,547 (GRCm38)	T799M	probably benign	Het
Anxa2	T	C	9: 69,488,081 (GRCm38)	Y202H	possibly damaging	Het
Arhgef33	A	G	17: 80,373,743 (GRCm38)	T771A	probably benign	Het
Atp12a	T	C	14: 56,372,589 (GRCm38)	V182A	probably benign	Het
Birc6	T	C	17: 74,612,286 (GRCm38)	L210S	probably damaging	Het
Car3	A	G	3: 14,864,432 (GRCm38)	T73A	probably benign	Het
Cd5l	T	C	3: 87,368,659 (GRCm38)	L312P	probably damaging	Het
Celf5	A	G	10: 81,467,304 (GRCm38)		probably benign	Het
Cep290	T	A	10: 100,496,810 (GRCm38)	V257E	probably damaging	Het
Cntrob	T	C	11: 69,320,867 (GRCm38)	D177G	possibly damaging	Het
Copg2	A	T	6: 30,810,336 (GRCm38)	F658I	probably damaging	Het
Csmd3	T	C	15: 47,899,739 (GRCm38)	T1234A	probably damaging	Het
Dhx35	A	G	2: 158,806,437 (GRCm38)	T72A	probably damaging	Het
Dmrtc2	A	T	7: 24,874,367 (GRCm38)	H209L	possibly damaging	Het
Eml5	G	T	12: 98,852,704 (GRCm38)		probably null	Het
Evpl	T	C	11: 116,223,660 (GRCm38)	E1068G	possibly damaging	Het
Ezh2	A	G	6: 47,576,660 (GRCm38)	M41T	probably damaging	Het
Fmo3	A	G	1: 162,968,725 (GRCm38)	S93P	possibly damaging	Het
Gdi2	A	G	13: 3,560,018 (GRCm38)	Y213C	possibly damaging	Het
Gpr15	A	T	16: 58,718,558 (GRCm38)	I56K	probably benign	Het
Gria2	G	T	3: 80,691,338 (GRCm38)	S796R	probably benign	Het
Hectd4	T	A	5: 121,291,191 (GRCm38)		probably benign	Het
Hgfac	T	C	5: 35,042,850 (GRCm38)		probably benign	Het
Hspg2	C	T	4: 137,520,156 (GRCm38)	R1200W	probably damaging	Het
Ift52	G	A	2: 163,025,355 (GRCm38)	D78N	possibly damaging	Het
Iqca	C	A	1: 90,081,416 (GRCm38)	W415L	probably damaging	Het
Ism1	A	T	2: 139,746,043 (GRCm38)	K236N	probably damaging	Het
Itgb6	C	T	2: 60,672,644 (GRCm38)	W43*	probably null	Het
Kcnk18	T	A	19: 59,235,341 (GRCm38)	I306N	probably damaging	Het
Kctd8	T	C	5: 69,340,560 (GRCm38)	K248E	probably damaging	Het
Layn	T	A	9: 51,059,533 (GRCm38)	I237F	probably benign	Het
Lce3f	C	T	3: 92,992,941 (GRCm38)	P23L	unknown	Het
Lct	A	G	1: 128,300,301 (GRCm38)	F1152L	probably damaging	Het
Mxra8	T	C	4: 155,843,074 (GRCm38)	I413T	probably damaging	Het
Nedd9	A	G	13: 41,317,962 (GRCm38)	V187A	probably benign	Het
Net1	A	G	13: 3,887,642 (GRCm38)	L207P	probably damaging	Het
Neurod1	G	T	2: 79,454,437 (GRCm38)	P201T	probably benign	Het
Nlrp1b	A	G	11: 71,161,821 (GRCm38)	F927S	probably damaging	Het
Nup98	A	C	7: 102,134,937 (GRCm38)	S1063A	probably benign	Het
Olfr1036	G	A	2: 86,074,760 (GRCm38)	V7I	possibly damaging	Het
Olfr1333	T	A	4: 118,829,868 (GRCm38)	M191L	probably benign	Het
Olfr1447	C	A	19: 12,901,235 (GRCm38)	V182F	probably benign	Het
Olfr215	T	C	6: 116,582,964 (GRCm38)		probably benign	Het
Olfr657	G	A	7: 104,636,159 (GRCm38)	V162I	probably benign	Het
Olfr747	G	T	14: 50,681,166 (GRCm38)	P156Q	possibly damaging	Het
Pdzd2	G	A	15: 12,592,460 (GRCm38)	R33W	probably damaging	Het
Phf21a	G	A	2: 92,330,515 (GRCm38)	V243I	probably damaging	Het
Ppp1r12b	A	G	1: 134,893,348 (GRCm38)		probably null	Het
Rexo5	T	C	7: 119,845,411 (GRCm38)	V703A	probably benign	Het
Rgs4	A	G	1: 169,745,278 (GRCm38)	S30P	probably benign	Het
Rrnad1	A	G	3: 87,923,817 (GRCm38)	S404P	probably damaging	Het
Rxra	C	A	2: 27,756,244 (GRCm38)	D340E	probably damaging	Het
Samhd1	A	G	2: 157,107,547 (GRCm38)	V473A	probably benign	Het
Scn3a	T	A	2: 65,472,342 (GRCm38)	K1253N	probably damaging	Het
Scn7a	T	C	2: 66,680,955 (GRCm38)	N1207S	probably benign	Het
Sec24d	T	A	3: 123,336,517 (GRCm38)	I443N	probably damaging	Het
Sema4g	T	A	19: 44,999,242 (GRCm38)		probably null	Het
Sema5b	A	G	16: 35,660,324 (GRCm38)	K787R	probably benign	Het
Serpinc1	A	G	1: 160,989,647 (GRCm38)	N104D	probably benign	Het
Sfn	T	C	4: 133,601,231 (GRCm38)	H180R	probably damaging	Het
Slc22a6	G	T	19: 8,619,107 (GRCm38)		probably null	Het
Slc9a8	T	C	2: 167,457,358 (GRCm38)	S217P	probably benign	Het
Smc6	A	G	12: 11,309,269 (GRCm38)	N965D	probably benign	Het
Sod2	T	A	17: 13,015,032 (GRCm38)	I177N	probably damaging	Het
Sp4	A	T	12: 118,299,600 (GRCm38)	I237K	probably damaging	Het
Sulf2	T	C	2: 166,079,612 (GRCm38)	K697R	probably benign	Het
Svs4	A	T	2: 164,277,085 (GRCm38)	D110E	unknown	Het
Tas1r1	T	A	4: 152,038,218 (GRCm38)	R57*	probably null	Het
Tlr5	T	C	1: 182,973,722 (GRCm38)	I197T	probably damaging	Het
Tmc3	T	C	7: 83,612,532 (GRCm38)	V606A	probably benign	Het
Tmem241	T	A	18: 12,118,412 (GRCm38)	L37F	probably damaging	Het
Tmem59l	A	T	8: 70,486,253 (GRCm38)	N90K	probably damaging	Het
Tram1	A	C	1: 13,576,456 (GRCm38)		probably benign	Het
Trim15	T	A	17: 36,865,169 (GRCm38)	H162L	probably benign	Het
Ttc28	T	A	5: 111,276,811 (GRCm38)	Y1501N	probably benign	Het
Ttc34	T	C	4: 154,862,214 (GRCm38)	V857A	probably benign	Het
Tulp4	A	G	17: 6,139,046 (GRCm38)	T48A	probably damaging	Het
Usp9y	T	C	Y: 1,368,089 (GRCm38)	E939G	probably damaging	Het
Utp20	A	G	10: 88,770,808 (GRCm38)	I1634T	probably benign	Het
Vmn2r72	T	C	7: 85,738,170 (GRCm38)	M729V	probably benign	Het
Vps13c	C	T	9: 67,881,447 (GRCm38)	T334M	probably damaging	Het
Wnk4	C	G	11: 101,276,340 (GRCm38)		probably benign	Het
Xpo1	A	G	11: 23,271,193 (GRCm38)	N97D	probably benign	Het
Xpo4	A	T	14: 57,603,672 (GRCm38)	F518Y	probably benign	Het
Zfp668	C	T	7: 127,866,606 (GRCm38)	V469I	possibly damaging	Het
Zfp85	C	A	13: 67,749,704 (GRCm38)	C83F	probably damaging	Het

Other mutations in Ntrk3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00424:Ntrk3	APN	7	78,250,873 (GRCm38)	missense	probably benign	0.03
IGL00862:Ntrk3	APN	7	78,247,177 (GRCm38)	missense	probably damaging	1.00
IGL00972:Ntrk3	APN	7	78,247,322 (GRCm38)	missense	possibly damaging	0.95
IGL00976:Ntrk3	APN	7	78,450,953 (GRCm38)	missense	probably benign	0.02
IGL02172:Ntrk3	APN	7	78,460,272 (GRCm38)	splice site	probably benign
IGL02175:Ntrk3	APN	7	78,247,228 (GRCm38)	missense	probably damaging	1.00
IGL02213:Ntrk3	APN	7	78,462,931 (GRCm38)	missense	probably benign	0.17
IGL02363:Ntrk3	APN	7	78,453,337 (GRCm38)	missense	probably benign	0.24
IGL02527:Ntrk3	APN	7	78,451,949 (GRCm38)	missense	probably benign
IGL02673:Ntrk3	APN	7	78,250,764 (GRCm38)	missense	probably damaging	1.00
IGL02755:Ntrk3	APN	7	78,460,439 (GRCm38)	missense	probably benign
IGL02998:Ntrk3	APN	7	78,577,657 (GRCm38)	missense	probably damaging	0.98
IGL03235:Ntrk3	APN	7	78,192,592 (GRCm38)	missense	probably damaging	1.00
R1465:Ntrk3	UTSW	7	78,356,014 (GRCm38)	splice site	probably benign
R1505:Ntrk3	UTSW	7	78,460,524 (GRCm38)	missense	probably damaging	0.99
R1638:Ntrk3	UTSW	7	78,247,288 (GRCm38)	missense	probably damaging	1.00
R1641:Ntrk3	UTSW	7	78,356,074 (GRCm38)	missense	probably damaging	1.00
R1786:Ntrk3	UTSW	7	78,477,935 (GRCm38)	splice site	probably benign
R1827:Ntrk3	UTSW	7	78,247,301 (GRCm38)	missense	probably damaging	1.00
R1868:Ntrk3	UTSW	7	78,192,604 (GRCm38)	missense	possibly damaging	0.90
R1873:Ntrk3	UTSW	7	78,462,839 (GRCm38)	missense	probably benign
R1929:Ntrk3	UTSW	7	78,516,723 (GRCm38)	splice site	probably null
R1941:Ntrk3	UTSW	7	78,247,262 (GRCm38)	missense	probably damaging	1.00
R2132:Ntrk3	UTSW	7	78,477,935 (GRCm38)	splice site	probably benign
R2214:Ntrk3	UTSW	7	78,516,772 (GRCm38)	missense	probably damaging	1.00
R2221:Ntrk3	UTSW	7	78,198,852 (GRCm38)	missense	probably damaging	1.00
R2223:Ntrk3	UTSW	7	78,198,852 (GRCm38)	missense	probably damaging	1.00
R2271:Ntrk3	UTSW	7	78,516,723 (GRCm38)	splice site	probably null
R2441:Ntrk3	UTSW	7	78,302,662 (GRCm38)	missense	probably damaging	1.00
R3108:Ntrk3	UTSW	7	78,460,515 (GRCm38)	missense	probably benign	0.01
R3109:Ntrk3	UTSW	7	78,460,515 (GRCm38)	missense	probably benign	0.01
R3959:Ntrk3	UTSW	7	78,198,842 (GRCm38)	missense	probably damaging	1.00
R4016:Ntrk3	UTSW	7	78,462,947 (GRCm38)	splice site	probably benign
R4028:Ntrk3	UTSW	7	78,192,710 (GRCm38)	missense	probably damaging	1.00
R4067:Ntrk3	UTSW	7	78,517,437 (GRCm38)	missense	probably damaging	1.00
R4398:Ntrk3	UTSW	7	78,250,769 (GRCm38)	nonsense	probably null
R4664:Ntrk3	UTSW	7	78,461,099 (GRCm38)	missense	probably damaging	0.99
R5045:Ntrk3	UTSW	7	78,460,424 (GRCm38)	missense	probably benign	0.13
R5081:Ntrk3	UTSW	7	78,577,774 (GRCm38)	missense	probably damaging	0.99
R5151:Ntrk3	UTSW	7	78,247,300 (GRCm38)	missense	probably damaging	1.00
R5249:Ntrk3	UTSW	7	78,461,166 (GRCm38)	missense	possibly damaging	0.87
R5294:Ntrk3	UTSW	7	78,517,506 (GRCm38)	splice site	probably null
R5594:Ntrk3	UTSW	7	78,451,899 (GRCm38)	missense	probably benign	0.10
R5923:Ntrk3	UTSW	7	78,451,928 (GRCm38)	missense	possibly damaging	0.61
R6878:Ntrk3	UTSW	7	78,304,372 (GRCm38)	missense	probably benign	0.00
R7083:Ntrk3	UTSW	7	78,250,839 (GRCm38)	missense	probably damaging	1.00
R7178:Ntrk3	UTSW	7	78,356,147 (GRCm38)	missense	possibly damaging	0.86
R7487:Ntrk3	UTSW	7	78,250,713 (GRCm38)	missense	probably damaging	1.00
R7607:Ntrk3	UTSW	7	78,250,873 (GRCm38)	missense	probably benign	0.03
R7800:Ntrk3	UTSW	7	78,302,740 (GRCm38)	missense	probably benign	0.09
R7961:Ntrk3	UTSW	7	78,453,328 (GRCm38)	missense	probably benign
R7976:Ntrk3	UTSW	7	78,356,206 (GRCm38)	missense	probably damaging	0.97
R8009:Ntrk3	UTSW	7	78,453,328 (GRCm38)	missense	probably benign
R8032:Ntrk3	UTSW	7	78,356,059 (GRCm38)	missense	probably damaging	1.00
R8104:Ntrk3	UTSW	7	78,577,702 (GRCm38)	missense	probably damaging	0.99
R8230:Ntrk3	UTSW	7	78,250,770 (GRCm38)	missense	probably damaging	1.00
R8254:Ntrk3	UTSW	7	78,192,578 (GRCm38)	missense	probably damaging	1.00
R8412:Ntrk3	UTSW	7	78,356,149 (GRCm38)	missense	probably benign	0.02
R8465:Ntrk3	UTSW	7	78,462,883 (GRCm38)	missense	probably damaging	0.99
R8841:Ntrk3	UTSW	7	78,356,093 (GRCm38)	missense	probably damaging	0.99
R9187:Ntrk3	UTSW	7	78,247,218 (GRCm38)	missense	possibly damaging	0.93
R9444:Ntrk3	UTSW	7	78,461,057 (GRCm38)	missense	probably damaging	1.00
R9475:Ntrk3	UTSW	7	78,302,732 (GRCm38)	missense	probably benign	0.27

Predicted Primers

PCR Primer
(F):5'- AAACATAGACTGTGGTCCTCCC -3'
(R):5'- CAGGTCCTGTGGCTGTTATCAG -3'

Sequencing Primer
(F):5'- ACTGGCATCCCCTTATCCAGG -3'
(R):5'- CTGTTATCAGTGGAGAGGAGGACTC -3'

Posted On

2014-06-23