Mutagenetix > Incidental Mutation

Incidental Mutation 'R9598:Chrna4'

723373

Institutional Source

Beutler Lab

Gene Symbol

Chrna4

Ensembl Gene

ENSMUSG00000027577

Gene Name

cholinergic receptor, nicotinic, alpha polypeptide 4

Synonyms

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

MMRRC Submission

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.172) question?

Stock #

R9598 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

180664104-180685339 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 180679264 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Leucine at position 61 (S61L)

Ref Sequence

ENSEMBL: ENSMUSP00000066338 (fasta)

Gene Model

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

AlphaFold

O70174

Predicted Effect

probably damaging
Transcript: ENSMUST00000067120
AA Change: S61L

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000066338
Gene: ENSMUSG00000027577
AA Change: S61L

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: S61L

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000104479
Gene: ENSMUSG00000027577
AA Change: S61L

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: S44L

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000123043
Gene: ENSMUSG00000027577
AA Change: S44L

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.8%

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: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4921539E11Rik	T	C	4: 103,088,604 (GRCm39)	I302V	probably benign	Het
Ackr2	A	C	9: 121,737,657 (GRCm39)	T11P	possibly damaging	Het
Ahnak	A	G	19: 8,981,149 (GRCm39)	N811S	probably benign	Het
Atm	T	C	9: 53,431,381 (GRCm39)	I326V	probably benign	Het
Ccn4	T	A	15: 66,784,764 (GRCm39)	C146S	possibly damaging	Het
Cdh23	A	T	10: 60,214,574 (GRCm39)	F1480L	probably benign	Het
Celsr2	T	C	3: 108,322,578 (GRCm39)	E78G	possibly damaging	Het
Ces1f	A	T	8: 93,983,494 (GRCm39)	N504K	probably benign	Het
Clcn3	G	T	8: 61,366,061 (GRCm39)	T864K	unknown	Het
Cym	A	C	3: 107,126,941 (GRCm39)	D71E	possibly damaging	Het
Ddx19b	T	C	8: 111,747,673 (GRCm39)	D87G	probably benign	Het
Dnah7b	T	C	1: 46,292,621 (GRCm39)	V3002A	possibly damaging	Het
Dnmt3a	G	A	12: 3,946,997 (GRCm39)	G408S	probably benign	Het
Dock10	A	T	1: 80,625,939 (GRCm39)	D66E	probably benign	Het
Dsg3	A	G	18: 20,672,789 (GRCm39)	D820G	probably damaging	Het
Dst	G	A	1: 34,153,014 (GRCm39)	V92I	possibly damaging	Het
Dusp16	T	A	6: 134,695,185 (GRCm39)	T549S	probably benign	Het
Ephx1	T	A	1: 180,827,381 (GRCm39)	K91*	probably null	Het
Flii	A	G	11: 60,617,991 (GRCm39)	F9L	probably benign	Het
Fmn2	T	C	1: 174,436,308 (GRCm39)	S760P	unknown	Het
Fmnl3	A	T	15: 99,223,210 (GRCm39)	V378E	probably damaging	Het
Gbp4	A	G	5: 105,284,740 (GRCm39)	S50P	probably damaging	Het
Glra3	G	T	8: 56,393,718 (GRCm39)		probably benign	Het
Gm10188	T	C	1: 132,157,033 (GRCm39)	D111G	unknown	Het
Gnptab	A	T	10: 88,247,876 (GRCm39)	E101V	probably damaging	Het
Hacl1	C	A	14: 31,332,197 (GRCm39)	M525I	probably benign	Het
Hid1	T	A	11: 115,239,738 (GRCm39)	T731S	probably damaging	Het
Ifi203	T	C	1: 173,751,522 (GRCm39)	Y847C	probably damaging	Het
Igfbpl1	C	A	4: 45,815,472 (GRCm39)	L221F	probably null	Het
Ighv1-12	A	G	12: 114,579,757 (GRCm39)	Y22H	probably benign	Het
Inpp5f	A	C	7: 128,278,515 (GRCm39)	D435A	possibly damaging	Het
L3mbtl4	T	A	17: 68,866,767 (GRCm39)	H335Q	probably benign	Het
Mapre2	A	G	18: 24,016,707 (GRCm39)	D287G	probably benign	Het
Mfsd14b	G	A	13: 65,214,522 (GRCm39)	R477W	probably benign	Het
Mfsd14b	C	A	13: 65,221,414 (GRCm39)	V293L	probably benign	Het
Msh4	A	T	3: 153,607,148 (GRCm39)	S131T	possibly damaging	Het
Nat8f2	A	T	6: 85,844,848 (GRCm39)	D171E	probably benign	Het
Ndufb5	G	T	3: 32,795,881 (GRCm39)	L24F	probably benign	Het
Nkain2	T	C	10: 32,278,291 (GRCm39)	I45V	probably damaging	Het
Nlrp9b	T	G	7: 19,753,302 (GRCm39)	M69R	probably benign	Het
Or4k37	A	T	2: 111,159,633 (GRCm39)	R290*	probably null	Het
Or5d39	A	C	2: 87,979,935 (GRCm39)	C143G	probably damaging	Het
Or5d46	A	T	2: 88,170,821 (GRCm39)	K304I	possibly damaging	Het
Oxct2b	T	A	4: 123,010,413 (GRCm39)	V111E	possibly damaging	Het
Parva	T	A	7: 112,187,753 (GRCm39)	V350D	probably damaging	Het
Pcdhb7	A	G	18: 37,475,434 (GRCm39)	D190G	probably damaging	Het
Pik3c2b	T	C	1: 133,012,725 (GRCm39)		probably null	Het
Plcz1	T	A	6: 139,985,484 (GRCm39)	Q19L	possibly damaging	Het
Prag1	A	G	8: 36,571,069 (GRCm39)	N551D	probably benign	Het
Rb1cc1	G	A	1: 6,310,189 (GRCm39)	V196I	probably damaging	Het
Rnf113a2	T	C	12: 84,464,270 (GRCm39)	V54A	probably benign	Het
Sec14l1	G	A	11: 117,044,102 (GRCm39)	E537K	probably damaging	Het
Shank1	G	A	7: 43,962,342 (GRCm39)	S71N	unknown	Het
Shtn1	T	A	19: 59,026,735 (GRCm39)	I119F	probably damaging	Het
Szt2	A	G	4: 118,266,358 (GRCm39)		probably null	Het
Tasp1	T	C	2: 139,819,567 (GRCm39)	D212G	probably benign	Het
Tmpo	A	G	10: 90,994,608 (GRCm39)		probably null	Het
Usp17lb	T	C	7: 104,489,718 (GRCm39)	K403R	probably benign	Het
Vcpip1	A	G	1: 9,816,019 (GRCm39)	V788A	probably benign	Het
Wdr25	C	A	12: 108,864,613 (GRCm39)	H253N	probably benign	Het
Wwc2	G	A	8: 48,328,360 (GRCm39)	S367L	probably damaging	Het
Zfr	A	G	15: 12,162,292 (GRCm39)	E814G	probably damaging	Het

Other mutations in Chrna4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00815:Chrna4	APN	2	180,671,184 (GRCm39)	missense	probably benign	0.09
IGL00914:Chrna4	APN	2	180,670,824 (GRCm39)	missense	probably damaging	1.00
IGL01511:Chrna4	APN	2	180,670,461 (GRCm39)	missense	probably benign	0.13
IGL02517:Chrna4	APN	2	180,670,926 (GRCm39)	missense	probably benign	0.01
IGL02715:Chrna4	APN	2	180,671,374 (GRCm39)	unclassified	probably benign
R1168:Chrna4	UTSW	2	180,675,931 (GRCm39)	missense	possibly damaging	0.61
R1475:Chrna4	UTSW	2	180,671,172 (GRCm39)	missense	probably benign	0.44
R1572:Chrna4	UTSW	2	180,671,100 (GRCm39)	missense	possibly damaging	0.95
R4428:Chrna4	UTSW	2	180,670,413 (GRCm39)	missense	probably damaging	0.99
R4429:Chrna4	UTSW	2	180,670,413 (GRCm39)	missense	probably damaging	0.99
R4431:Chrna4	UTSW	2	180,670,413 (GRCm39)	missense	probably damaging	0.99
R4494:Chrna4	UTSW	2	180,670,281 (GRCm39)	missense	probably damaging	0.98
R4664:Chrna4	UTSW	2	180,679,286 (GRCm39)	missense	probably damaging	1.00
R4666:Chrna4	UTSW	2	180,679,286 (GRCm39)	missense	probably damaging	1.00
R4931:Chrna4	UTSW	2	180,670,665 (GRCm39)	missense	probably benign	0.00
R5144:Chrna4	UTSW	2	180,666,623 (GRCm39)	missense	probably damaging	1.00
R5556:Chrna4	UTSW	2	180,675,773 (GRCm39)	missense	possibly damaging	0.94
R5633:Chrna4	UTSW	2	180,671,253 (GRCm39)	missense	probably damaging	1.00
R5889:Chrna4	UTSW	2	180,670,451 (GRCm39)	missense	probably damaging	1.00
R6056:Chrna4	UTSW	2	180,671,235 (GRCm39)	missense	probably damaging	1.00
R6120:Chrna4	UTSW	2	180,666,599 (GRCm39)	missense	probably damaging	1.00
R7030:Chrna4	UTSW	2	180,671,334 (GRCm39)	missense	probably damaging	1.00
R7352:Chrna4	UTSW	2	180,679,267 (GRCm39)	missense	probably damaging	0.97
R7694:Chrna4	UTSW	2	180,660,386 (GRCm39)	missense
R7945:Chrna4	UTSW	2	180,670,454 (GRCm39)	missense	probably benign	0.04
R8075:Chrna4	UTSW	2	180,680,859 (GRCm39)	missense	unknown
R8706:Chrna4	UTSW	2	180,679,307 (GRCm39)	missense	probably damaging	1.00
R9091:Chrna4	UTSW	2	180,670,643 (GRCm39)	missense	possibly damaging	0.79
R9138:Chrna4	UTSW	2	180,670,775 (GRCm39)	missense	probably damaging	0.97
R9154:Chrna4	UTSW	2	180,670,602 (GRCm39)	missense	probably damaging	0.99
R9270:Chrna4	UTSW	2	180,670,643 (GRCm39)	missense	possibly damaging	0.79
Z1177:Chrna4	UTSW	2	180,670,078 (GRCm39)	missense	possibly damaging	0.80
Z1177:Chrna4	UTSW	2	180,666,606 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

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

Sequencing Primer
(F):5'- AGGATGACATTTTGCTGGCAACC -3'
(R):5'- GCTCCTGAAGAGACTCTT -3'

Posted On

2022-08-09