Mutagenetix > Incidental Mutation

Incidental Mutation 'R0049:Ngf'

16138

Institutional Source

Beutler Lab

Gene Symbol

Ngf

Ensembl Gene

ENSMUSG00000027859

Gene Name

nerve growth factor

Synonyms

Ngfb

MMRRC Submission

038343-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.668) question?

Stock #

R0049 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

102377235-102428329 bp(+) (GRCm39)

Type of Mutation

nonsense

DNA Base Change (assembly)

A to T at 102427661 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Stop codon at position 137 (R137*)

Ref Sequence

ENSEMBL: ENSMUSP00000142801 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000035952] [ENSMUST00000106925] [ENSMUST00000198644]

AlphaFold

P01139

Predicted Effect

probably null
Transcript: ENSMUST00000035952
AA Change: R75*

SMART Domains

Protein: ENSMUSP00000040345
Gene: ENSMUSG00000027859
AA Change: R75*

Domain	Start	End	E-Value	Type
signal peptide	1	18	N/A	INTRINSIC
NGF	128	232	1.41e-78	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000106925
AA Change: R141*

SMART Domains

Protein: ENSMUSP00000102538
Gene: ENSMUSG00000027859
AA Change: R141*

Domain	Start	End	E-Value	Type
NGF	194	298	1.41e-78	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000198644
AA Change: R137*

SMART Domains

Protein: ENSMUSP00000142801
Gene: ENSMUSG00000027859
AA Change: R137*

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC
NGF	190	294	7.1e-81	SMART

Meta Mutation Damage Score

0.9755

Coding Region Coverage

1x: 90.0%
3x: 87.7%
10x: 82.4%
20x: 74.6%

Validation Efficiency

89% (108/122)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the NGF-beta family and encodes a secreted protein which homodimerizes and is incorporated into a larger complex. This protein has nerve growth stimulating activity and the complex is involved in the regulation of growth and the differentiation of sympathetic and certain sensory neurons. Mutations in this gene have been associated with hereditary sensory and autonomic neuropathy, type 5 (HSAN5), and dysregulation of this gene's expression is associated with allergic rhinitis. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous null mutants exhibit elevated pain threshold, loss of neurons in both sensory and sympathetic ganglia, but diminished apoptosis in the retina and spinal cord. Heterozygotes exhibit a substantially reduced number of sympathetic neurons. [provided by MGI curators]

Allele List at MGI

All alleles(3) : Targeted(3)

Other mutations in this stock

Total: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A2m	A	T	6: 121,615,267 (GRCm39)	H9L	possibly damaging	Het
Aars1	T	A	8: 111,779,083 (GRCm39)	I739K	possibly damaging	Het
Acod1	T	A	14: 103,292,643 (GRCm39)	I389K	possibly damaging	Het
Akap1	C	A	11: 88,730,450 (GRCm39)		probably null	Het
Anxa7	T	C	14: 20,512,678 (GRCm39)	D285G	probably damaging	Het
Arhgap1	T	C	2: 91,500,514 (GRCm39)	Y308H	probably damaging	Het
Arhgef11	T	A	3: 87,636,500 (GRCm39)		probably null	Het
Atosb	A	T	4: 43,036,441 (GRCm39)	S97T	probably benign	Het
Atp6v0a4	G	A	6: 38,059,016 (GRCm39)	R256C	probably damaging	Het
Camsap3	C	A	8: 3,648,772 (GRCm39)	S163R	probably benign	Het
Ccdc110	A	T	8: 46,395,663 (GRCm39)	E518V	probably damaging	Het
Ccdc180	G	A	4: 45,930,119 (GRCm39)		probably null	Het
Ccnt1	T	C	15: 98,462,960 (GRCm39)	M71V	probably benign	Het
Celsr2	T	A	3: 108,304,570 (GRCm39)	Y2263F	probably benign	Het
Cfap69	T	C	5: 5,663,734 (GRCm39)	T498A	probably benign	Het
Clstn3	T	A	6: 124,436,812 (GRCm39)	I132F	possibly damaging	Het
Cnot4	A	G	6: 35,028,212 (GRCm39)	V468A	probably benign	Het
Crmp1	T	G	5: 37,422,617 (GRCm39)	D141E	possibly damaging	Het
Cryz	C	A	3: 154,317,189 (GRCm39)	A136D	probably damaging	Het
Dcst2	T	C	3: 89,278,913 (GRCm39)	V550A	probably benign	Het
Dph6	A	G	2: 114,353,525 (GRCm39)	V221A	probably benign	Het
Ecm2	A	T	13: 49,677,922 (GRCm39)	K403*	probably null	Het
Eif3d	T	C	15: 77,843,924 (GRCm39)	N474S	probably benign	Het
F12	T	C	13: 55,574,130 (GRCm39)	D34G	probably benign	Het
Fam228b	A	T	12: 4,798,117 (GRCm39)	F200Y	probably damaging	Het
Fgl2	T	A	5: 21,580,661 (GRCm39)	D334E	possibly damaging	Het
Fras1	T	A	5: 96,924,481 (GRCm39)	F3641I	probably benign	Het
Gabrb2	T	G	11: 42,484,674 (GRCm39)	Y244D	probably damaging	Het
Gcc1	A	T	6: 28,421,268 (GRCm39)	D16E	probably benign	Het
Gm10648	T	C	7: 28,561,202 (GRCm39)		probably benign	Het
Gorasp2	T	C	2: 70,521,067 (GRCm39)	S346P	possibly damaging	Het
Htt	A	C	5: 35,066,006 (GRCm39)	K3060N	probably damaging	Het
Ibsp	C	T	5: 104,450,024 (GRCm39)	L8F	probably damaging	Het
Kif27	A	T	13: 58,451,378 (GRCm39)	D983E	probably damaging	Het
Kif3a	T	A	11: 53,481,560 (GRCm39)		probably benign	Het
Kif3c	A	C	12: 3,417,090 (GRCm39)	K370N	possibly damaging	Het
Loxhd1	T	C	18: 77,468,256 (GRCm39)		probably benign	Het
Maz	A	T	7: 126,623,758 (GRCm39)	D74E	probably damaging	Het
Med21	T	C	6: 146,551,732 (GRCm39)	S128P	probably damaging	Het
Mms19	A	C	19: 41,943,607 (GRCm39)	M374R	probably damaging	Het
Mrpl3	T	C	9: 104,932,872 (GRCm39)	V111A	probably benign	Het
Mtfr2	T	A	10: 20,224,158 (GRCm39)	Y31N	probably damaging	Het
Neb	A	C	2: 52,060,479 (GRCm39)	M2286R	possibly damaging	Het
Nr1i3	T	A	1: 171,041,982 (GRCm39)	V22E	probably damaging	Het
Nxpe5	T	C	5: 138,249,566 (GRCm39)	V452A	probably damaging	Het
Or11g27	A	T	14: 50,771,151 (GRCm39)	K94M	probably damaging	Het
Pax3	A	G	1: 78,080,141 (GRCm39)	L415P	probably damaging	Het
Pcnt	G	T	10: 76,205,655 (GRCm39)		probably benign	Het
Peg3	G	T	7: 6,714,672 (GRCm39)	D183E	possibly damaging	Het
Pglyrp1	G	T	7: 18,623,313 (GRCm39)	G120V	probably damaging	Het
Pomt1	T	A	2: 32,142,023 (GRCm39)	H584Q	possibly damaging	Het
Prkcq	G	A	2: 11,288,643 (GRCm39)	G532E	probably benign	Het
Pwp1	A	G	10: 85,721,480 (GRCm39)	T361A	possibly damaging	Het
Rab4a	A	T	8: 124,554,081 (GRCm39)	H5L	probably damaging	Het
Ramp1	T	C	1: 91,124,592 (GRCm39)	I51T	possibly damaging	Het
Raph1	G	T	1: 60,565,058 (GRCm39)	T143K	probably benign	Het
Rhpn1	A	G	15: 75,581,088 (GRCm39)	E110G	possibly damaging	Het
Rnf168	A	T	16: 32,117,287 (GRCm39)	T283S	possibly damaging	Het
Ros1	T	A	10: 51,977,857 (GRCm39)	Y1463F	possibly damaging	Het
Rtn4ip1	A	G	10: 43,797,430 (GRCm39)	Q223R	probably null	Het
Rtp4	G	T	16: 23,431,679 (GRCm39)	M70I	probably benign	Het
Sag	C	A	1: 87,762,340 (GRCm39)	T335K	probably damaging	Het
Sgo1	C	T	17: 53,986,691 (GRCm39)	D167N	probably damaging	Het
Slco1a8	T	C	6: 141,936,147 (GRCm39)	T313A	probably benign	Het
St6gal1	G	T	16: 23,139,891 (GRCm39)	A21S	probably damaging	Het
Stard9	C	A	2: 120,530,300 (GRCm39)	L2186I	probably damaging	Het
Sun2	T	A	15: 79,611,810 (GRCm39)		probably benign	Het
Taf4	G	A	2: 179,565,884 (GRCm39)	T849M	probably damaging	Het
Taok2	G	A	7: 126,465,583 (GRCm39)	H404Y	possibly damaging	Het
Tdrd7	A	G	4: 45,987,582 (GRCm39)	I72V	probably damaging	Het
Trav1	T	A	14: 52,666,155 (GRCm39)	S52T	probably damaging	Het
Trim30a	C	T	7: 104,078,559 (GRCm39)		probably null	Het
Tro	T	C	X: 149,437,565 (GRCm39)	N364S	possibly damaging	Het
Tshz3	A	G	7: 36,469,534 (GRCm39)	T508A	probably damaging	Het
Ttc21b	A	G	2: 66,053,908 (GRCm39)	L757P	probably damaging	Het
Vmn1r218	C	T	13: 23,321,225 (GRCm39)	Q111*	probably null	Het
Vmn2r75	G	A	7: 85,797,309 (GRCm39)	Q835*	probably null	Het
Xcr1	T	A	9: 123,684,940 (GRCm39)	D274V	possibly damaging	Het
Ypel5	C	T	17: 73,153,332 (GRCm39)	T12I	probably benign	Het

Other mutations in Ngf

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00555:Ngf	APN	3	102,427,788 (GRCm39)	missense	probably damaging	0.99
IGL01344:Ngf	APN	3	102,427,628 (GRCm39)	missense	probably benign	0.00
R0049:Ngf	UTSW	3	102,427,661 (GRCm39)	nonsense	probably null
R0147:Ngf	UTSW	3	102,417,119 (GRCm39)	intron	probably benign
R0148:Ngf	UTSW	3	102,417,119 (GRCm39)	intron	probably benign
R0149:Ngf	UTSW	3	102,427,762 (GRCm39)	missense	probably benign	0.13
R1769:Ngf	UTSW	3	102,427,513 (GRCm39)	missense	possibly damaging	0.87
R4357:Ngf	UTSW	3	102,427,521 (GRCm39)	missense	probably benign	0.22
R4486:Ngf	UTSW	3	102,428,015 (GRCm39)	missense	probably damaging	1.00
R4487:Ngf	UTSW	3	102,428,015 (GRCm39)	missense	probably damaging	1.00
R4488:Ngf	UTSW	3	102,428,015 (GRCm39)	missense	probably damaging	1.00
R4817:Ngf	UTSW	3	102,417,156 (GRCm39)	intron	probably benign
R4883:Ngf	UTSW	3	102,427,961 (GRCm39)	missense	probably damaging	1.00
R4938:Ngf	UTSW	3	102,427,790 (GRCm39)	missense	probably damaging	1.00
R5158:Ngf	UTSW	3	102,427,445 (GRCm39)	missense	possibly damaging	0.82
R5681:Ngf	UTSW	3	102,427,669 (GRCm39)	missense	probably damaging	1.00
R6259:Ngf	UTSW	3	102,417,113 (GRCm39)	intron	probably benign
R7790:Ngf	UTSW	3	102,417,140 (GRCm39)	missense	unknown
R8544:Ngf	UTSW	3	102,427,991 (GRCm39)	missense	probably damaging	1.00
R9794:Ngf	UTSW	3	102,428,132 (GRCm39)	missense	probably damaging	1.00

Protein Function and Prediction

NGF is a neurotrophin, one of a group of secreted proteins that promotes the growth, differentiation, and survival of neurons in the central and peripheral nervous system via the tyrosine kinase receptors TrkA, TrkB, TrkC and p75(NTR) (1-5). In addition, neurotrophins function in bidirectional signaling between immune cells and the neurosensory network in the airway and skin (6).

Background

Mutations in NGFB (alternatively, NGF) are linked to hereditary sensory and autonomic neuropathy type V [(7;8); OMIM: # 608654].

Ngf^{tm1Gne/tm1Gne}; MGI:1857535

involves: 129S7/SvEvBrd

Homozygotes have defects in the dorsal root ganglion (5).

Ngf^{tm1Gne/tm1Gne}; MGI:1857535

involves: 129S7/SvEvBrd * C57BL/6

In this genetic background, homozygotes mutants exhibit elevated pain threshold, loss of neurons in both sensory and sympathetic ganglia, but diminished apoptosis in the retina and spinal cord (9). Heterozygotes exhibit a substantially reduced number of sympathetic neurons.

References

1. Levi-Montalcini, R., and Angeletti, P. U. (1968) Nerve Growth Factor. Physiol Rev. 48, 534-569.

2. Martinotti, G., Di Iorio, G., Marini, S., Ricci, V., De Berardis, D., and Di Giannantonio, M. (2012) Nerve Growth Factor and Brain-Derived Neurotrophic Factor Concentrations in Schizophrenia: A Review. J Biol Regul Homeost Agents. 26, 347-356.

3. Ichim, G., Tauszig-Delamasure, S., and Mehlen, P. (2012) Neurotrophins and Cell Death. Exp Cell Res. 318, 1221-1228.

4. Huang, E. J., and Reichardt, L. F. (2003) Trk Receptors: Roles in Neuronal Signal Transduction. Annu Rev Biochem. 72, 609-642.

5. Mandai, K., Guo, T., St Hillaire, C., Meabon, J. S., Kanning, K. C., Bothwell, M., and Ginty, D. D. (2009) LIG Family Receptor Tyrosine Kinase-Associated Proteins Modulate Growth Factor Signals during Neural Development. Neuron. 63, 614-627.

6. Scuri, M., Samsell, L., and Piedimonte, G. (2010) The Role of Neurotrophins in Inflammation and Allergy. Inflamm Allergy Drug Targets. 9, 173-180.

7. Carvalho, O. P., Thornton, G. K., Hertecant, J., Houlden, H., Nicholas, A. K., Cox, J. J., Rielly, M., Al-Gazali, L., and Woods, C. G. (2011) A Novel NGF Mutation Clarifies the Molecular Mechanism and Extends the Phenotypic Spectrum of the HSAN5 Neuropathy. J Med Genet. 48, 131-135.

8. Einarsdottir, E., Carlsson, A., Minde, J., Toolanen, G., Svensson, O., Solders, G., Holmgren, G., Holmberg, D., and Holmberg, M. (2004) A Mutation in the Nerve Growth Factor Beta Gene (NGFB) Causes Loss of Pain Perception. Hum Mol Genet. 13, 799-805.

9. Crowley, C., Spencer, S. D., Nishimura, M. C., Chen, K. S., Pitts-Meek, S., Armanini, M. P., Ling, L. H., McMahon, S. B., Shelton, D. L., and Levinson, A. D. (1994) Mice Lacking Nerve Growth Factor Display Perinatal Loss of Sensory and Sympathetic Neurons Yet Develop Basal Forebrain Cholinergic Neurons. Cell. 76, 1001-1011.

Posted On

2013-01-08

Science Writer

Anne Murray