Mutagenetix > Incidental Mutation

Incidental Mutation 'R4666:Chrna4'

351890

Institutional Source

Beutler Lab

Gene Symbol

Chrna4

Ensembl Gene

ENSMUSG00000027577

Gene Name

cholinergic receptor, nicotinic, alpha polypeptide 4

Synonyms

alpha4 nAChR, Acra-4, a4 nicotinic receptor, Acra4, alpha4-nAChR

MMRRC Submission

041924-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.141) question?

Stock #

R4666 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

181018380-181043546 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 181037493 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 54 (S54P)

Ref Sequence

ENSEMBL: ENSMUSP00000104479 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000067120] [ENSMUST00000108851] [ENSMUST00000124400]

AlphaFold

O70174

Predicted Effect

probably damaging
Transcript: ENSMUST00000067120
AA Change: S54P

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

SMART Domains

Protein: ENSMUSP00000066338
Gene: ENSMUSG00000027577
AA Change: S54P

Domain	Start	End	E-Value	Type
signal peptide	1	30	N/A	INTRINSIC
Pfam:Neur_chan_LBD	39	245	1.4e-76	PFAM
Pfam:Neur_chan_memb	252	620	1.9e-107	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000108851
AA Change: S54P

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

SMART Domains

Protein: ENSMUSP00000104479
Gene: ENSMUSG00000027577
AA Change: S54P

Domain	Start	End	E-Value	Type
signal peptide	1	30	N/A	INTRINSIC
Pfam:Neur_chan_LBD	39	245	8.4e-79	PFAM
Pfam:Neur_chan_memb	252	620	3.3e-112	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000124400
AA Change: S37P

PolyPhen 2 Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000123043
Gene: ENSMUSG00000027577
AA Change: S37P

Domain	Start	End	E-Value	Type
Pfam:Neur_chan_LBD	22	78	3.6e-19	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135766

SMART Domains

Protein: ENSMUSP00000125724
Gene: ENSMUSG00000027577

Domain	Start	End	E-Value	Type
signal peptide	1	30	N/A	INTRINSIC
Pfam:Neur_chan_LBD	39	130	9.2e-37	PFAM

Meta Mutation Damage Score

0.6455

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.5%
20x: 95.8%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a nicotinic acetylcholine receptor, which belongs to a superfamily of ligand-gated ion channels that play a role in fast signal transmission at synapses. These pentameric receptors can bind acetylcholine, which causes an extensive change in conformation that leads to the opening of an ion-conducting channel across the plasma membrane. This protein is an integral membrane receptor subunit that can interact with either nAChR beta-2 or nAChR beta-4 to form a functional receptor. Mutations in this gene cause nocturnal frontal lobe epilepsy type 1. Polymorphisms in this gene that provide protection against nicotine addiction have been described. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]
PHENOTYPE: Nullizygous mice may show reduced chemically-elicited analgesia, susceptibility to seizures, increased anxiety, and altered behavioral responses to nicotine or a new environment. Homozygotes for any of several knock-in alleles exhibit altered nervous system physiology and/or sensitivity to nicotine. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 100 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2410137M14Rik	G	A	17: 36,978,902 (GRCm38)	S12L	probably benign	Het
Abce1	A	G	8: 79,687,486 (GRCm38)	V532A	probably damaging	Het
Adamts12	T	A	15: 11,311,492 (GRCm38)	N1278K	probably benign	Het
Adipor1	T	A	1: 134,424,905 (GRCm38)	I138N	probably damaging	Het
Aox2	C	T	1: 58,304,597 (GRCm38)	Q480*	probably null	Het
Arhgef38	C	T	3: 133,140,772 (GRCm38)		probably null	Het
Atmin	A	G	8: 116,957,959 (GRCm38)	D786G	probably damaging	Het
Bltp3a	G	T	17: 27,893,503 (GRCm38)	W1222L	possibly damaging	Het
Capn1	A	T	19: 6,011,015 (GRCm38)	N253K	probably benign	Het
Cdh8	T	C	8: 99,024,902 (GRCm38)	T728A	possibly damaging	Het
Celsr1	A	G	15: 86,030,494 (GRCm38)	S1093P	probably damaging	Het
Cep135	C	A	5: 76,616,854 (GRCm38)	P560T	probably benign	Het
Chfr	C	T	5: 110,144,867 (GRCm38)	Q167*	probably null	Het
Cntln	A	G	4: 84,971,216 (GRCm38)	N312S	probably benign	Het
Cntn6	A	G	6: 104,728,284 (GRCm38)	E154G	probably benign	Het
Col6a6	T	A	9: 105,767,342 (GRCm38)	Y1249F	possibly damaging	Het
Cpsf2	T	C	12: 101,983,207 (GRCm38)	S61P	probably damaging	Het
Cpvl	C	T	6: 53,931,933 (GRCm38)	E282K	probably benign	Het
Cryba2	C	T	1: 74,890,048 (GRCm38)	D179N	probably benign	Het
Daglb	A	T	5: 143,503,349 (GRCm38)	R654W	probably damaging	Het
Dennd3	A	G	15: 73,570,860 (GRCm38)	D1244G	probably damaging	Het
Dhx57	T	C	17: 80,274,961 (GRCm38)	E405G	probably damaging	Het
Dnah10	T	C	5: 124,828,472 (GRCm38)	M4060T	possibly damaging	Het
Dph1	A	G	11: 75,181,330 (GRCm38)	S238P	probably damaging	Het
Duox1	C	T	2: 122,319,475 (GRCm38)	P116S	probably benign	Het
Ebf1	A	G	11: 44,991,557 (GRCm38)	N447D	probably damaging	Het
Epg5	A	G	18: 78,012,864 (GRCm38)	N1751S	probably benign	Het
Exoc6	A	G	19: 37,570,505 (GRCm38)	D75G	probably damaging	Het
Extl2	T	A	3: 116,024,207 (GRCm38)	I70N	probably damaging	Het
Fanca	T	C	8: 123,268,972 (GRCm38)	T1364A	probably damaging	Het
Fbln7	T	A	2: 128,894,910 (GRCm38)		probably null	Het
Foxa3	G	T	7: 19,014,372 (GRCm38)	C275*	probably null	Het
Foxred1	C	T	9: 35,210,855 (GRCm38)		probably benign	Het
Galr2	A	G	11: 116,283,629 (GRCm38)	T362A	probably benign	Het
Garem2	C	A	5: 30,114,667 (GRCm38)	R376S	probably damaging	Het
Garre1	T	C	7: 34,284,773 (GRCm38)	M142V	probably damaging	Het
Gatc	T	A	5: 115,335,547 (GRCm38)	N111I	probably benign	Het
Gjb4	C	A	4: 127,351,778 (GRCm38)	K123N	probably damaging	Het
Gm9894	T	C	13: 67,765,094 (GRCm38)		noncoding transcript	Het
Gtdc1	T	C	2: 44,591,925 (GRCm38)	N301S	probably benign	Het
Gtf2ird1	T	A	5: 134,383,902 (GRCm38)	E55V	probably damaging	Het
Gtsf1	T	C	15: 103,421,205 (GRCm38)	I96V	probably benign	Het
Homer1	T	A	13: 93,402,159 (GRCm38)	I170N	probably damaging	Het
Homer3	G	A	8: 70,290,143 (GRCm38)		probably null	Het
Hoxb9	A	G	11: 96,274,831 (GRCm38)	K242R	possibly damaging	Het
Ifna14	T	C	4: 88,571,336 (GRCm38)	R155G	probably benign	Het
Lrrc7	GAAGTTGTTTGGAGATTCTTATCTTA	GA	3: 158,318,408 (GRCm38)		probably benign	Het
Lsm11	A	G	11: 45,933,813 (GRCm38)	S296P	probably damaging	Het
Macrod2	T	C	2: 142,217,599 (GRCm38)	L265P	probably damaging	Het
Mcu	G	A	10: 59,456,699 (GRCm38)	L53F	probably damaging	Het
Mpv17l2	A	G	8: 70,760,415 (GRCm38)	V104A	possibly damaging	Het
Myh10	G	A	11: 68,801,730 (GRCm38)		probably null	Het
Nemf	T	C	12: 69,312,280 (GRCm38)	E1031G	probably damaging	Het
Nhsl1	G	A	10: 18,531,405 (GRCm38)	S1395N	probably damaging	Het
Niban3	G	T	8: 71,603,825 (GRCm38)	E390*	probably null	Het
Nlrp2	T	A	7: 5,319,189 (GRCm38)	I82F	probably benign	Het
Nlrp4e	T	A	7: 23,336,780 (GRCm38)	L686*	probably null	Het
Nudt12os	T	A	17: 59,024,551 (GRCm38)		noncoding transcript	Het
Or10ag57	T	A	2: 87,387,876 (GRCm38)	I57K	probably damaging	Het
Or10j5	G	A	1: 172,957,590 (GRCm38)	S265N	probably benign	Het
Or2h1b	A	T	17: 37,151,379 (GRCm38)	S44T	possibly damaging	Het
Or5ac23	A	G	16: 59,329,210 (GRCm38)	Y100H	possibly damaging	Het
Or5k16	T	C	16: 58,916,584 (GRCm38)	D19G	probably benign	Het
Or8g27	T	A	9: 39,217,846 (GRCm38)	M163K	probably damaging	Het
Pde7a	T	C	3: 19,260,256 (GRCm38)	T59A	probably damaging	Het
Pde7b	A	C	10: 20,438,750 (GRCm38)	D203E	probably damaging	Het
Phkg2	T	A	7: 127,577,984 (GRCm38)	I94N	possibly damaging	Het
Pik3r2	G	A	8: 70,768,859 (GRCm38)	T667I	possibly damaging	Het
Pitx3	T	A	19: 46,137,101 (GRCm38)	H68L	possibly damaging	Het
Prcd	A	G	11: 116,668,164 (GRCm38)		probably benign	Het
Prune2	C	T	19: 17,120,188 (GRCm38)	R1019*	probably null	Het
Psap	A	G	10: 60,300,545 (GRCm38)	D486G	probably benign	Het
Purb	A	T	11: 6,475,615 (GRCm38)	V91E	probably damaging	Het
Recql	C	A	6: 142,376,841 (GRCm38)	V112F	probably damaging	Het
Rptor	A	T	11: 119,743,882 (GRCm38)	I175F	probably damaging	Het
Sbf1	C	T	15: 89,295,246 (GRCm38)	V1385M	probably damaging	Het
Serpinb13	C	T	1: 106,982,844 (GRCm38)	S66L	probably damaging	Het
Slc35f6	T	C	5: 30,655,613 (GRCm38)	L37P	probably damaging	Het
Slc6a3	T	A	13: 73,538,581 (GRCm38)	N22K	possibly damaging	Het
Sorl1	A	T	9: 42,004,051 (GRCm38)	M1294K	probably damaging	Het
Sp6	C	A	11: 97,021,875 (GRCm38)	A138E	probably benign	Het
Spag8	G	T	4: 43,653,408 (GRCm38)		probably benign	Het
Spmip4	G	T	6: 50,595,828 (GRCm38)	T35K	possibly damaging	Het
Spon1	T	A	7: 114,028,969 (GRCm38)	M320K	probably benign	Het
Tceanc2	A	T	4: 107,165,560 (GRCm38)	S77T	probably damaging	Het
Thsd7a	T	A	6: 12,337,314 (GRCm38)	T1235S	possibly damaging	Het
Thsd7a	T	A	6: 12,504,013 (GRCm38)	I381F	possibly damaging	Het
Tmc4	T	C	7: 3,671,271 (GRCm38)		probably null	Het
Tmprss11d	T	C	5: 86,309,401 (GRCm38)	D133G	probably damaging	Het
Trav13n-3	T	A	14: 53,337,496 (GRCm38)	V65D	probably damaging	Het
Trpm1	G	T	7: 64,203,034 (GRCm38)	L65F	probably damaging	Het
Tyk2	C	T	9: 21,114,207 (GRCm38)	A741T	probably damaging	Het
Ube2v1	T	A	2: 167,610,377 (GRCm38)	Y102F	probably damaging	Het
Uckl1	A	T	2: 181,574,868 (GRCm38)	S95T	possibly damaging	Het
Vcan	C	A	13: 89,679,934 (GRCm38)	W2171L	probably damaging	Het
Vinac1	T	C	2: 129,038,230 (GRCm38)	H592R	probably benign	Het
Vmn1r64	T	C	7: 5,884,358 (GRCm38)	N62S	probably damaging	Het
Vmn2r67	T	C	7: 85,150,623 (GRCm38)	D469G	probably benign	Het
Vps13b	A	G	15: 35,640,544 (GRCm38)	S1352G	probably benign	Het
Zbtb38	C	T	9: 96,688,383 (GRCm38)	R216H	probably damaging	Het

Other mutations in Chrna4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00815:Chrna4	APN	2	181,029,391 (GRCm38)	missense	probably benign	0.09
IGL00914:Chrna4	APN	2	181,029,031 (GRCm38)	missense	probably damaging	1.00
IGL01511:Chrna4	APN	2	181,028,668 (GRCm38)	missense	probably benign	0.13
IGL02517:Chrna4	APN	2	181,029,133 (GRCm38)	missense	probably benign	0.01
IGL02715:Chrna4	APN	2	181,029,581 (GRCm38)	unclassified	probably benign
R1168:Chrna4	UTSW	2	181,034,138 (GRCm38)	missense	possibly damaging	0.61
R1475:Chrna4	UTSW	2	181,029,379 (GRCm38)	missense	probably benign	0.44
R1572:Chrna4	UTSW	2	181,029,307 (GRCm38)	missense	possibly damaging	0.95
R4428:Chrna4	UTSW	2	181,028,620 (GRCm38)	missense	probably damaging	0.99
R4429:Chrna4	UTSW	2	181,028,620 (GRCm38)	missense	probably damaging	0.99
R4431:Chrna4	UTSW	2	181,028,620 (GRCm38)	missense	probably damaging	0.99
R4494:Chrna4	UTSW	2	181,028,488 (GRCm38)	missense	probably damaging	0.98
R4664:Chrna4	UTSW	2	181,037,493 (GRCm38)	missense	probably damaging	1.00
R4931:Chrna4	UTSW	2	181,028,872 (GRCm38)	missense	probably benign	0.00
R5144:Chrna4	UTSW	2	181,024,830 (GRCm38)	missense	probably damaging	1.00
R5556:Chrna4	UTSW	2	181,033,980 (GRCm38)	missense	possibly damaging	0.94
R5633:Chrna4	UTSW	2	181,029,460 (GRCm38)	missense	probably damaging	1.00
R5889:Chrna4	UTSW	2	181,028,658 (GRCm38)	missense	probably damaging	1.00
R6056:Chrna4	UTSW	2	181,029,442 (GRCm38)	missense	probably damaging	1.00
R6120:Chrna4	UTSW	2	181,024,806 (GRCm38)	missense	probably damaging	1.00
R7030:Chrna4	UTSW	2	181,029,541 (GRCm38)	missense	probably damaging	1.00
R7352:Chrna4	UTSW	2	181,037,474 (GRCm38)	missense	probably damaging	0.97
R7694:Chrna4	UTSW	2	181,018,593 (GRCm38)	missense
R7945:Chrna4	UTSW	2	181,028,661 (GRCm38)	missense	probably benign	0.04
R8075:Chrna4	UTSW	2	181,039,066 (GRCm38)	missense	unknown
R8706:Chrna4	UTSW	2	181,037,514 (GRCm38)	missense	probably damaging	1.00
R9091:Chrna4	UTSW	2	181,028,850 (GRCm38)	missense	possibly damaging	0.79
R9138:Chrna4	UTSW	2	181,028,982 (GRCm38)	missense	probably damaging	0.97
R9154:Chrna4	UTSW	2	181,028,809 (GRCm38)	missense	probably damaging	0.99
R9270:Chrna4	UTSW	2	181,028,850 (GRCm38)	missense	possibly damaging	0.79
R9598:Chrna4	UTSW	2	181,037,471 (GRCm38)	missense	probably damaging	1.00
Z1177:Chrna4	UTSW	2	181,028,285 (GRCm38)	missense	possibly damaging	0.80
Z1177:Chrna4	UTSW	2	181,024,813 (GRCm38)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- AACCTTGGTTGAACCCAGCC -3'
(R):5'- ATTCTTGGGGCCCTGGAAAG -3'

Sequencing Primer
(F):5'- CCACATGGAGTCTCAGTGTGATAAC -3'
(R):5'- AGCTAGCAGCCACATAGA -3'

Posted On

2015-10-08